Deep Brain Stimulation Helps Neuropathic Pain

Today's post from newswise.com (see link below) talks about one of the latest stories concerning neuropathic pain treatment and that is deep brain stimulation. This is where a small electrode is inserted into the brain and activated to produce an electrical signal designed to interrupt abnormal activity. It's precisely this sort of research which gives us hope that it won't be too long before pain can be controlled without resorting to powerful drugs. However, it will probably never be cheap, or available to all, even if it is proved to be of benefit to all people living with chronic pain. That said, it looks as though it may well be an effective option for some patients and that must be a good thing.

For Some, Deep Brain Stimulation Brings Lasting Improvement in Neuropathic Pain
Released: 2/13/2013 10:00 AM EST
Source Newsroom: Wolters Kluwer Health: Lippincott Williams & Wilkins


Large Study Shows Continued Improvement with Longer Follow-up, Reports Neurosurgery

Newswise — Philadelphia, Pa. (February 13, 2013) – For many patients with difficult-to-treat neuropathic pain, deep brain stimulation (DBS) can lead to long-term improvement in pain scores and other outcomes, according to a study in the February issue of Neurosurgery, official journal of theCongress of Neurological Surgeons. The journal is published by Lippincott Williams & Wilkins, a part of Wolters Kluwer Health.

About two-thirds of eligible patients who undergo DBS achieve significant and lasting benefits in terms of pain, quality of life, and overall health, according to the report by Sandra G.J. Boccard, PhD, and colleagues of University of Oxford, led by Tipu Aziz FMedSci and Alex Green, MD. Some outcomes show continued improvement after the first year, according to the new report, which is one of the largest studies of DBS for neuropathic pain performed to date.

Most Patients Benefit from DBS for Neuropathic Pain
The authors reviewed their 12-year experience with DBS for neuropathic pain. Neuropathic pain is a common and difficult-to-treat type of pain caused by nerve damage, seen in patients with trauma, diabetes, and other conditions. Phantom limb pain after amputation is an example of neuropathic pain.

In DBS, a small electrode is surgically placed in a precise location in the brain. A mild electrical current is delivered to stimulate that area of the brain, with the goal of interrupting abnormal activity. Deep brain stimulation has become a standard and effective treatment for movement disorders such as Parkinson's disease. Although DBS has also been used to treat various types of chronic pain, its role in patients with neuropathic pain remains unclear.

Between 1999 and 2011, that authors' program evaluated 197 patients with chronic neuropathic pain for eligibility for DBS. Of these, 85 patients proceeded to DBS treatment. The remaining patients did not receive DBS—most commonly because they were unable to secure funding from the U.K. National Health Service or decided not to undergo electrode placement surgery.

The patients who underwent DBS were 60 men and 25 women, average age 52 years. Stroke was the most common cause of neuropathic pain, followed by head and face pain, spinal disease, amputation, and injury to nerves from the upper spinal cord (brachial plexus).

In 74 patients, a trial of DBS produced sufficient pain relief to proceed with implantation of an electrical pulse generator. Of 59 patients with sufficient follow-up data, 39 had significant improvement in their overall health status up to four years later. Thus, 66 percent of patients "gained benefit and efficacy" by undergoing DBS.

Benefits Vary by Cause; Some Outcomes Improve with Time
The benefits of DBS varied for patients with different causes of neuropathic pain. Treatment was beneficial for 89 percent for patients with amputation and 70 percent of those with stroke, compared to 50 percent of those with brachial plexus injury.

On average, scores on a 10-point pain scale (with 10 indicating the most severe pain) decreased from about 8 to 4 within the first three months, remaining about the same with longer follow-up. Continued follow-up in a small number of patients suggested further improvement in other outcomes, including quality-of-life scores.

Deep brain stimulation has long been regarded as potentially useful for patients with severe neuropathic pain that is not relieved by other treatments. However, because of the difficulties of performing studies of this highly specialized treatment, there has been relatively little research to confirm its benefits; only about 1,500 patients have been treated worldwide. The new study—accounting for about five percent of all reported patients—used up-to-date DBS technologies, imaging, and surgical techniques.

Dr. Boccard and coauthors acknowledge some important limitations of their study—especially the lack of complete patient follow-up. However, they believe their experience is sufficiently encouraging to warrant additional studies, especially with continued advances in stimulation approaches and technology. The researchers conclude, "Clinical trials retaining patients in long-term follow-up are desirable to confirm findings from prospectively assessed case series."

About Neurosurgery
Neurosurgery, the Official Journal of the Congress of Neurological Surgeons, is your most complete window to the contemporary field of neurosurgery. Members of the Congress and non-member subscribers receive 3,000 pages per year packed with the very latest science, technology, and medicine, not to mention full-text online access to the world's most complete, up-to-the-minute neurosurgery resource. For professionals aware of the rapid pace of developments in the field, Neurosurgery is nothing short of indispensable.

About Lippincott Williams & Wilkins
Lippincott Williams & Wilkins (LWW) is a leading international publisher of trusted content delivered in innovative ways to practitioners, professionals and students to learn new skills, stay current on their practice, and make important decisions to improve patient care and clinical outcomes.
LWW is part of Wolters Kluwer Health, a leading global provider of information, business intelligence and point-of-care solutions for the healthcare industry. Wolters Kluwer Health is part of Wolters Kluwer, a market-leading global information services company with 2011 annual revenues of €3.4 billion ($4.7 billion).


http://www.newswise.com/articles/for-some-deep-brain-stimulation-brings-lasting-improvement-in-neuropathic-pain?ret=/articles/list&category=medicine&page=1&search[status]=3&search[sort]=date+desc&search[section]=10&search[has_multimedia]=

Neuropathic Pain Whats Going On

Today's excellent post from painblogr.org (see link below) looks at the nature of pain and may well help you understand what's happening to you when you suffer from nerve pain. It's a confusing area (every neuropathy patient will testify to that) but this article explains the basics of pain in such a way that the reader can go:'ok, so that's what's happening inside my brain'. Believe me, every consultation with a doctor or specialist will be a lot clearer if you've already absorbed this basic information. Worth a read.

Explainer: what is pain and what is happening when we feel it?
Lorimer Moseley Posted on: November 19, 2015

“If someone has a pain in his hand […] one does not comfort the hand, but the sufferer.” – Philosopher Ludwig Wittgenstein, 1953

What is pain? It might seem like an easy question. The answer, however, depends on who you ask.

Some say pain is a warning signal that something is damaged, but what about pain-free major trauma? Some say pain is the body’s way of telling you something is wrong, but what about phantom limb pain, where the painful body part is not even there?

Pain scientists are reasonably agreed that pain is an unpleasant feeling in our body that makes us want to stop and change our behaviour. We no longer think of pain as a measure of tissue damage – it doesn’t actually work that way even in highly controlled experiments. We now think of pain as a complex and highly sophisticated protective mechanism.
How does pain work?

Our body contains specialised nerves that detect potentially dangerous changes in temperature, chemical balance or pressure. These “danger detectors” (or “nociceptors”) send alerts to the brain, but they cannot send pain to the brain because all pain is made by the brain.

When you’re injured, the brain makes an educated guess which part of the body is in danger and produces the pain there. Pain is not actually coming from the wrist you broke, or the ankle you sprained. Pain is the result of the brain evaluating information, including danger data from the danger detection system, cognitive data such as expectations, previous exposure, cultural and social norms and beliefs, and other sensory data such as what you see, hear and otherwise sense.

The brain produces pain. Where in the body the brain produces the pain is a “best guess scenario”, based on all the incoming data and stored information. Usually the brain gets it right, but sometimes it doesn’t. An example is referred pain in your leg when it is your back that might need the protecting.

It is pain that tells us not to do things – for example, not to lift with an injured hand, or not to walk with an injured foot. It is pain, too, that tells us to do things – see a physio, visit a GP, sit still and rest.

We now know that pain can be “turned on” or “turned up” by anything that provides the brain with credible evidence that the body is in danger and needs protecting.

All in your head?

So is pain all about the brain and not at all about the body? No, these “danger detectors” are distributed across almost all of our body tissues and act as the eyes of the brain.

When there is a sudden change in tissue environment – for example, it heats up, gets acidic (cyclists, imagine the lactic acid burn at the end of a sprint), is squashed, squeezed, pulled or pinched – these danger detectors are our first line of defence.

They alert the brain and mobilise inflammatory mechanisms that increase blood flow and cause the release of healing molecules from nearby tissue, thus triggering the repair process.

Local anaesthetic renders these danger detectors useless, so danger messages are not triggered. As such, we can be pain-free despite major tissue trauma, such as being cut into for an operation. Just because pain comes from the brain, it doesn’t mean it’s all in your head.

Inflammation, on the other hand, renders these danger detectors more sensitive, so they respond to situations that are not actually dangerous. For example, when you move an inflamed joint, it hurts a long way before the tissues of the joint are actually stressed.

Danger messages travel to the brain and are highly processed along the way, with the brain itself taking part in the processing. The danger transmission neurones that run up the spinal cord to the brain are under real-time control from the brain, increasing and decreasing their sensitivity according to what the brain suggests would be helpful.

So, if the brain’s evaluation of all available information leads it to conclude that things are truly dangerous, then the danger transmission system becomes more sensitive (called descending facilitation). If the brain concludes things are not truly dangerous, then the danger transmission system becomes less sensitive (called descending inhibition).

Danger evaluation in the brain is mindbogglingly complex. Many brain regions are involved, some more commonly that others, but the exact mix of brain regions varies between individuals and, in fact, between moments within individuals.

To understand how pain emerges into consciousness requires us to understand how consciousness itself emerges, and that is proving to be very tricky.

To understand how pain works in real-life people with real-life pain, we can apply a reasonably easy principle: any credible evidence that the body is in danger and protective behaviour would be helpful will increase the likelihood and intensity of pain. Any credible evidence that the body is safe will decrease the likelihood and intensity of pain. It is as simple and as difficult as that. 

Implications

To reduce pain, we need to reduce credible evidence of danger and increase credible evidence of safety. Danger detectors can be turned off by local anaesthetic, and we can also stimulate the body’s own danger-reduction pathways and mechanisms. This can be done by anything that is associated with safety – most obviously accurate understanding of how pain really works, exercise, active coping strategies, safe people and places.

A very effective way to reduce pain is to make something else seem more important to the brain – this is called distraction. Only being unconscious or dead provide greater pain relief than distraction.

In chronic pain the sensitivity of the hardware (the biological structures) increases so the relationship between pain and the true need for protection becomes distorted: we become over-protected by pain.

This is one significant reason there is no quick fix for nearly all persistent pains. Recovery requires a journey of patience, persistence, courage and good coaching. The best interventions focus on slowly training our body and brain to be less protective.

This article was originally published on The Conversation. Read the original article here.

The article is the first in our series on Pain. Further articles will explore who pain affects, how we describe and experience pain across cultures and genders, and the effect of chronic pain on the economy.

Lorimer Moseley, is Professor of Clinical Neurosciences and Foundation Chair in Physiotherapy, University of South Australia

http://painblogr.org/explainer-what-is-pain-and-what-is-happening-when-we-feel-it

Stocking To Detect Neuropathic Foot Wounds

Today's post from diabetes.co.uk (see link below) talks about a new, prototype product designed to help neuropathy patients who have lost so much feeling from their feet that they become prone to injury, pressure sores and open wounds (without realising it). It's a stocking with inbuilt sensors that monitors unduly high pressures on the foot and alerts the wearer to the problem before it causes physical injury. The problem is that it's currently only a prototype and is probably going to be very expensive but if it gets past the development stage, it could be a very useful tool which will hopefully prevent the nasty injuries loss of feeling in the feet can cause.

New pressure-monitoring device could prevent neuropathy-related injuries
Thu, 14 May 2015

Researchers from Germany have developed a pressure-monitoring stocking that could prevent foot wounds in people with diabetic neuropathy.

The device, which was developed by researchers at the Fraunhofer Institute for Silicate Research ISC in Würzburg, uses integrated sensors to send warnings when pressure on the foot is too high, essentially performing the job of the nerves in the feet.
Neuropathy and foot pressure Diabetic neuropathy is one of the most common diabetic complications. Over time, prolonged exposure to high blood glucose levels damages the nerves in the feet. Diabetic neuropathy is the leading cause of amputation in the UK.

When people develop diabetic neuropathy, they lose the feeling in their feet. This can have a number of damaging effects. One such effect is the inability to notice the amount of pressure being placed on the feet. People without diabetic neuropathy have functioning nerve pathways that automatically redistribute when the person is standing up for a long time.

Over time, excessive weight placed on the feet can lead to the development of pressure sores, which can in turn lead to open wounds or damaged foot tissue.
How does the pressure stocking work? The stocking features 40 dielectric elastomer sensors that measures pressure distribution. The sensors are made from a special silicone film. When pressure builds on the foot - usually because of standing in the same place for a while - the sensors transmit a signal to a wireless electronics unit.

The stocking will cost around £180.
What makes the pressure stocking different? There are several products available to balance out pressure on the foot for people with diabetes, but this one is different, according to Dr. Bernhard Brunner, of the Fraunhofer institute:

"Existing systems on the market measure the pressure distribution only on the bottom of the foot using shoe inserts. Our sensors are attached to the stocking's sole, at the hell, the top of the foot and the ankle, so they can take readings in three dimensions. This is a totally new approach."
Moving forward The device is brand new, and some creases still to be ironed out. Dr. Brunner explained the challenges that face the team going forward:

"With the current prototype, the electronics are attached to the end of the stocking. We're planning to relocate them to a small, button-sized housing that can be detached with a hook-and-loop fastening strip. There's no way around this until a reliable method for cleaning the electronics is developed."

The sensors have to be washable, too. "The first washability tests are in planning, but cleaning using disinfectant is no problem."

The researchers have filed a patent application for the stockings. From May 19 to May 20, the team will be presenting a prototype of the stockings at the SENSOR+TEST 2015 Measurement Fair in Nuremberg.

http://www.diabetes.co.uk/news/2015/may/new-pressure-monitoring-device-could-prevent-neuropathy-related-injuries-97065315.html

Tapentadol A New Alternative For Neuropathic Pain

Today's post comes from marketwatch.com (see link below) and is a press release for Tapentadol, a new centrally-acting opioid made by Janssen Pharmceuticals to control neuropathic pain. Far be it from me to promote either a company or an opioid but we're always looking for alternatives to the treatments that either don't work, or have unpleasant side effects. This is another opium derivative, so there will undoubtedly be issues regarding side effects and addiction for some people but the tests look promising. The post is long because Janssen have provided a complete description of how the drug works and what the potential side effects may be and that's worth reading. One assumes that this information will all appear on the leaflet inside the box when the drug achieves general release. Tapentadol will not be for everybody, as is the case for all similar treatments but it may be a breakthrough for some. Time will tell.
More information about Tapentadol can be found here (and is easier to digest),

Phase 3 Data Show NUCYNTA® ER (tapentadol) Extended-Release Tablets Provide Pain Management for Patients with Diabetic Peripheral Neuropathy (DPN)

Study results presented at the 31st Annual Scientific Meeting of the American Pain Society

press release May 17, 2012,

RARITAN, N.J., May 17, 2012 /PRNewswire via COMTEX/ -- Janssen Pharmaceuticals, Inc. today announced the results of an investigational Phase 3 study suggesting NUCYNTA® ER (tapentadol) extended-release tablets were significantly more effective than placebo in providing pain management among adults with chronic moderate to severe, painful diabetic peripheral neuropathy (DPN). Results of the study were presented at the 31st Annual Scientific Meeting of the American Pain Society being held May 16-19 in Honolulu, Hawaii.

Diabetes affects nearly 26 million people in the United States(1)- and its prevalence is expected to grow significantly during the coming decades(2). Over time, people with diabetes can develop a type of nerve damage called neuropathy. Approximately 60 to 70 percent of people with diabetes have some form of neuropathy(3). The most common type is diabetic peripheral neuropathy, which causes pain or loss of feeling in the toes, feet, legs, hands, and arms.

The study found, among patients who had at least a one-point reduction in pain intensity during three weeks of treatment with tapentadol ER, those who continued on an optimized dose of tapentadol ER (100-250 mg twice daily) for an additional 12 weeks experienced significantly better pain control compared to those who switched to placebo(4). Treatment-emergent adverse events reported in 10 percent or more of tapentadol ER-treated patients during the double-blind maintenance period included nausea (21.1 percent) and vomiting (12.7 percent)(4).

"Painful DPN is a common and burdensome complication of diabetes, and controlling pain in people with DPN can be challenging," said Aaron I. Vinik, M.D., Ph.D., FCP, MACP, Director of Research and Neuroendocrine Unit at Strelitz Diabetes Center for Endocrine and Metabolic Disorders at Eastern Virginia Medical School, and lead investigator of the study. "These data suggest tapentadol ER provides a significant reduction in chronic pain in adult patients with DPN."

The findings of this study are consistent with those of another Janssen-sponsored study published early last year, which found tapentadol ER to be effective versus placebo for relieving moderate to severe chronic pain associated with diabetic peripheral neuropathy.

"We are pleased the Phase 3 data presented today showed tapentadol ER was effective at providing pain management for patients with chronic, moderate to severe pain associated with DPN," said Christine Rauschkolb, M.D., Ph.D., Vice President and Head of Integrated Operations, Janssen Research & Development, LLC and one of the study's authors. "Janssen has a long history of helping physicians provide responsible treatment for patients to relieve their acute and chronic pain. We are committed to developing new pain management options for the millions of Americans who have painful DPN."

About the Study

This Phase 3 clinical trial was a randomized-withdrawal, placebo-controlled study. It enrolled adult patients who had moderate to severe, chronic painful DPN for six months or more and a history of analgesic use for painful DPN for three months or more. This trial had three phases: an open-label phase, which included a 3-week titration period during which the individually optimized tapentadol ER dose (100-250 mg two times per day) was determined for each patient; a 12-week, double-blind maintenance phase, during which patients with a one-point or greater reduction in pain intensity from beginning to end of titration were randomized either to continue taking tapentadol ER (at their optimal dose) or to receive placebo; and a follow-up period with a clinic visit at four days and a telephone interview at 10 to 14 days after discontinuation of study drug.

The primary efficacy endpoint of the study was the mean change in average pain intensity from baseline (point of randomization) to the last week of the 12-week, double-blind maintenance phase, as determined by an 11-point pain rating scale or numerical rating scale (NRS; 0='no pain,' 10='pain as bad as you can imagine'). Safety assessments were performed on the open-label and double-blind safety populations (all patients who received greater than or equal to 1 dose of open-label and double-blind treatment, respectively). Treatment-emergent adverse events (TEAEs), defined as any AEs (new or worse in intensity) that occurred after the first intake of study drug during the open-label or double-blind phase, were monitored throughout the study.

In the open-label titration period, 459 patients received one or more doses of tapentadol ER and were included in the open-label safety population. At the start of the 3-week, open-label phase, the majority of patients (87.1 percent) reported severe pain (6 or more on the 11-point NRS) with a mean pain intensity of 7.3. By the end of the open-label phase, the mean pain intensity was reduced to 3.6. Treatment-emergent adverse events (TEAEs) experienced by 10 percent or more of patients during the open-label phase were nausea (24.4 percent), dizziness (17), constipation (11.8) and somnolence (10.7).

A total of 358 patients completed the open-label titration period; 318 were randomized and received one or more dose of study medication (n=152 for placebo, 166 for tapentadol ER).

Following randomization, during the double-blind treatment phase to week 12, pain increased in the placebo group (as demonstrated by the mean change in pain intensity of 1.3), while in the tapentadol ER group, efficacy was maintained, as indicated by the mean change in pain intensity of 0.28. The least-squares mean difference between the tapentadol ER and placebo groups in the change in average pain intensity was -0.95 on the 11-point NRS favoring tapentadol ER (95 percent CI, -1.42 to -0.49; p<0.001, tapentadol ER vs. placebo)(4).

For more details about the study design, please visit www.clinicaltrials.gov (NCT01041859).

Janssen Research & Development, LLC and Grunenthal GmbH, conducted this study, which Janssen Research & Development, LLC has included as part of its Supplemental New Drug Application (sNDA) submitted on October 28, 2011 to the U.S. Food and Drug Administration (FDA) for tapentadol ER tablets for the management of neuropathic pain associated with DPN in patients 18 years of age or older. The FDA currently is reviewing this supplemental application.

About Tapentadol and NUCYNTA® ER

Tapentadol is a centrally-acting synthetic analgesic. The tapentadol molecule is classified as Schedule II of the Controlled Substances Act.

NUCYNTA® ER (tapentadol) extended-release tablets are an oral analgesic available by prescription only and indicated for the management of moderate to severe chronic pain in adults when a continuous, around-the-clock opioid analgesic is needed for an extended period of time. NUCYNTA® ER is taken twice daily and available in 50 mg, 100 mg, 150 mg, 200 mg and 250 mg strengths.

Outside the United States, tapentadol is marketed by Janssen Inc. in Canada; Grünenthal GmbH discovered tapentadol and markets immediate- and extended-release formulations of tapentadol (PALEXIA®) in various countries in Europe.

IMPORTANT SAFETY INFORMATION FOR NUCYNTA® ER (tapentadol) extended-release tablets

WARNING: POTENTIAL FOR ABUSE, PROPER PATIENT SELECTION, AND LIMITATIONS OF USE

Potential for Abuse

NUCYNTA® ER contains tapentadol, a mu-opioid agonist and a Schedule II controlled substance with an abuse liability similar to other opioid analgesics.

NUCYNTA® ER can be abused in a manner similar to other opioid agonists, legal or illicit. These risks should be considered when prescribing or dispensing NUCYNTA® ER in situations where the physician or pharmacist is concerned about an increased risk of misuse, abuse, or diversion. Schedule II opioid substances, which include hydromorphone, morphine, oxycodone, fentanyl, oxymorphone, and methadone, have the highest potential for abuse and risk of fatal overdose due to respiratory depression.

Proper Patient Selection

NUCYNTA® ER is an extended-release formulation of tapentadol indicated for the management of moderate to severe chronic pain in adults when a continuous, around-the-clock opioid analgesic is needed for an extended period of time.

Limitations of Use

NUCYNTA® ER is not intended for use as an as-needed analgesic.

NUCYNTA® ER is not intended for the management of acute or postoperative pain.

NUCYNTA® ER tablets are to be swallowed whole and are not to be split, broken, chewed, dissolved, or crushed. Taking split, broken, chewed, dissolved, or crushed NUCYNTA® ER tablets could lead to rapid release and absorption of a potentially fatal dose of tapentadol.

Patients must not consume alcoholic beverages, or prescription or nonprescription medications containing alcohol. Co-ingestion of alcohol with NUCYNTA® ER may result in a potentially fatal overdose of tapentadol.

CONTRADICTIONS

NUCYNTA® ER is contraindicated in patients with significant respiratory depression, acute or severe bronchial asthma or hypercapnia in unmonitored settings or in the absence of resuscitative equipment.

NUCYNTA® ER is contraindicated in any patient who has or is suspected of having a paralytic ileus.

NUCYNTA® ER is contraindicated in patients who are receiving monoamine oxidase inhibitors (MAOIs) or who have taken them within the last 14 days due to potential additive effects on norepinephrine levels, which may result in adverse cardiovascular events.

NUCYNTA® ER is contraindicated in patients with a known hypersensitivity to the active substance, tapentadol, or any component of the product. Angioedema has been reported in association with use of tapentadol.

WARNINGS & PRECAUTIONS

NUCYNTA® ER tablets are to be swallowed whole and are not to be split, broken, chewed, dissolved, or crushed. Taking split, broken, chewed, crushed, or dissolved NUCYNTA® ER tablets leads to the rapid release and absorption of a potentially fatal dose of tapentadol.

NUCYNTA® ER tablets must be kept in a secure place out of the reach of children. Accidental consumption of NUCYNTA® ER, especially in children, can result in a fatal overdose of tapentadol.

Respiratory depression is the primary risk of mu-opioid agonists. Respiratory depression occurs more frequently in elderly or debilitated patients and in those suffering from conditions accompanied by hypoxia, hypercapnia, or upper airway obstruction, in whom even moderate therapeutic doses may significantly decrease pulmonary ventilation.

Use NUCYNTA® ER with caution in patients with conditions accompanied by hypoxia, hypercapnia, or decreased respiratory reserve, such as: asthma, chronic obstructive pulmonary disease or cor pulmonale, severe obesity, sleep apnea syndrome, myxedema, kyphoscoliosis, central nervous system (CNS) depression, or coma. In such patients, even usual therapeutic doses of NUCYNTA® ER may increase airway resistance and decrease respiratory drive to the point of apnea. Alternative non-mu-opioid agonist analgesics should be considered, and NUCYNTA® ER should be employed only under careful medical supervision at the lowest effective dose in such patients. If respiratory depression occurs, it should be treated as any mu-opioid agonist-induced respiratory depression.

Patients receiving other opioid agonist analgesics, general anesthetics, phenothiazines, other tranquilizers, sedatives, hypnotics, centrally acting muscle relaxants, or other CNS depressants (including alcohol) concomitantly with NUCYNTA® ER may exhibit additive CNS depression. Interactive effects resulting in respiratory depression, hypotension, profound sedation, coma, or death may result if these drugs are taken in combination with NUCYNTA® ER. When such combined therapy is contemplated, a dose reduction of one or both agents should be considered.

Opioid analgesics can raise cerebrospinal fluid pressure as a result of respiratory depression with carbon dioxide retention. Therefore, NUCYNTA® ER should not be used in patients who may be susceptible to the effects of raised cerebrospinal fluid pressure, such as those with evidence of head injury and increased intracranial pressure. Opioid analgesics may obscure the clinical course of patients with head injury due to effects on pupillary response and consciousness. NUCYNTA® ER should be used with caution in patients with head injury, intracranial lesions, or other sources of preexisting increased intracranial pressure.

Tapentadol is a mu-opioid agonist and is a Schedule II controlled substance. Such drugs are sought by drug abusers and people with addiction disorders. Diversion of Schedule II products is an act subject to criminal penalty.

Patients should be assessed for their clinical risks for opioid abuse or addiction prior to being prescribed opioids.

NUCYNTA® ER can be abused in a manner similar to other opioid agonists, legal or illicit. This should be considered when prescribing or dispensing NUCYNTA® ER in situations where the physician or pharmacist is concerned about an increased risk of misuse and abuse. Concerns about abuse and addiction should not prevent the proper management of pain. However, all patients treated with mu-opioid agonists require careful monitoring for signs of abuse and addiction, since use of mu-opioid agonist analgesic products carries the risk of addiction even under appropriate medical use.

Drug abusers may attempt to abuse NUCYNTA® ER by crushing, chewing, snorting, or injecting the product. These practices may result in the uncontrolled delivery of NUCYNTA® ER and pose a significant risk to the abuser that could result in overdose and death.

NUCYNTA® ER may cause severe hypotension. Patients at higher risk of hypotension include those with hypovolemia or those taking concurrent products that compromise vasomotor tone (eg, phenothiazines, general anesthetics).

Patients should be cautioned that NUCYNTA® ER may impair the mental and/or physical abilities required for the performance of potentially hazardous tasks such as driving a car or operating machinery. This is to be expected, especially at the beginning of treatment, at any change of dosage, as well as in combination with alcohol or tranquilizers.

NUCYNTA® ER may be expected to have additive effects when used in conjunction with alcohol, other opioids, or illicit drugs that cause CNS depression, because respiratory depression, hypotension, hypertension, and profound sedation, coma, or death may result.

NUCYNTA® ER has not been evaluated in patients with a predisposition to a seizure disorder, and such patients were excluded from clinical studies. As with other opioids, NUCYNTA® ER should be prescribed with care in patients with a history of a seizure disorder or any condition that would put the patient at risk of seizures.

Cases of life-threatening serotonin syndrome have been reported with the concurrent use of tapentadol and serotonergic drugs. Serotonergic drugs comprise selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), triptans, drugs that affect the serotonergic neurotransmitter system (eg, mirtazapine, trazodone, and tramadol), and drugs that impair metabolism of serotonin (including MAOIs). This may occur within the recommended dose. Serotonin syndrome may include mental-status changes (eg, agitation, hallucinations, coma), autonomic instability (eg, tachycardia, labile blood pressure, hyperthermia), neuromuscular aberrations (eg, hyperreflexia, incoordination) and/or gastrointestinal symptoms (eg, nausea, vomiting, diarrhea), and can be fatal.

Withdrawal symptoms may occur if NUCYNTA® ER is discontinued abruptly. These symptoms may include: anxiety, sweating, insomnia, rigors, pain, nausea, tremors, diarrhea, upper respiratory symptoms, piloerection, and rarely, hallucinations. Withdrawal symptoms may be reduced by tapering NUCYNTA® ER.

A study with the immediate-release formulation of tapentadol in subjects with hepatic impairment showed higher serum concentrations of tapentadol than in those with normal hepatic function. Tapentadol should be used with caution in patients with moderate hepatic impairment.

NUCYNTA® ER has not been studied in patients with severe hepatic impairment, and use in this population is not recommended.

Like other drugs with mu-opioid agonist activity, NUCYNTA® ER may cause spasm of the sphincter of Oddi and should be used with caution in patients with biliary tract disease, including acute pancreatitis.

NUCYNTA® ER should be used with caution in the following conditions: adrenocortical insufficiency (eg, Addison's disease); delirium tremens; myxedema or hypothyroidism; prostatic hypertrophy or urethral stricture; and toxic psychosis.

Pregnancy Category C. There are no adequate and well-controlled studies of NUCYNTA® ER in pregnant women. NUCYNTA® ER should be used during pregnancy ONLY if the potential benefit justifies the potential risk to the fetus.

ADVERSE REACTIONS

The most common (greater than equal to 10%) adverse reactions were nausea, constipation, headache, dizziness, and somnolence.

About Janssen Pharmaceuticals, Inc. and Janssen Research and Development, LLC

At Janssen, we are dedicated to addressing and solving some of the most important unmet medical needs of our time in oncology, immunology, neuroscience, infectious diseases and vaccines, and cardiovascular and metabolic diseases. Driven by our commitment to patients, we develop and bring innovative products, services and solutions to people throughout the world.

Janssen Pharmaceuticals, Inc., and Janssen Research & Development, LLC are part of the Janssen Pharmaceutical Companies.

Janssen Pharmaceuticals, Inc. provides medicines for an array of health concerns in several therapeutic areas. Innovative therapies Janssen Pharmaceuticals, Inc. offers currently include ACIPHEX® (rabeprazole sodium), DORIBAX® (doripenem for injection), ELMIRON® (pentosan polysulfate sodium), NUCYNTA® (tapentadol), NUCYNTA® ER (tapentadol) extended-release tablets and XARELTO® (rivaroxaban) tablets. The full prescribing information for NUCYNTA® ER, including boxed warnings, is available here; the full prescribing information for XARELTO®, including boxed warnings, is available here.

For more information on Janssen Pharmaceuticals, Inc., visit us at www.janssenpharmaceuticalsinc.com or follow us on Twitter at www.twitter.com/JanssenUS .

For more information on Janssen Research & Development, LLC, visit us at http://www.janssenrnd.com/ .

http://www.marketwatch.com/story/phase-3-data-show-nucynta-er-tapentadol-extended-release-tablets-provide-pain-management-for-patients-with-diabetic-peripheral-neuropathy-dpn-2012-05-17

Erectile Disfunction Can Be A Neuropathic Problem

Today's post from uk-med.co.uk (see link below) talks about erectile disfunction, the elephant in the room for many men living with neuropathy. Women can have problems in this area too, especially concerning dryness but this article concentrates on men. For once it is a study which looks at the problem from another angle, in that it looked at men with impotence and found that many of them also suffered from neuropathic problems. Usually, ED is seen as a possible side effect of neuropathy but it can also be said that neuropathy is a co-problem with erectile disfunction. Many people don't need studies to know that ED can be a depressing problem to add to the symptoms of neuropathy but dicussing it with your doctor may lead to satisfactory modern treatments improving the situation.

Smoking doesn't help guys!

 Neuropathic Pain Connection With Erectile Dysfunction

       
A recent research paper written by Dr Consuelo Valles-Antuna at the University Central de Asturias in Spain, has found a connection between nerve impairment in the peripheral nervous system and its effect on erectile dysfunction.

 They studied 90 patients that displayed acute signs of peripheral neuropathy and the added problem of erectile dysfunction, needing intensive therapy. Current drug treatments for erectile dysfunction include Viagra and Cialis.

Patients that volunteered for the research had an average age of 54 years, 10% under 40 years and 2% were over 70. No interconnection with the IIEF-5 (International Index of Erectile Function) summary was found in the older test subjects, by way of making them more susceptible, if anything the younger participants had lower IIEF-5 scores. Breakdown of other medical backgrounds was; 30% cardiovascular disease, 16% neurogenic conditions, 16% diabetes, 7% mental health and 11% no risk factors.

Those presenting with worse cases of peripheral neuropathy also had very low IIEF-5 results. Neurophysiological investigations supported evidence that 69% had neurological pathology and 8% of these had myelopathy, which affects the spinal cord. Over a third had polyneuropathy, with small percentages were exhibiting small fibre and pudendal neuropathy, which causes problems in the pelvic area.

 Dr Valles-Antuna believes that this is a unique study, that covers the full spectrum of peripheral nerve fibre conditions in a non-selected group presenting with erectile dysfunction. Using the information gathered from the sufferers, combined with neurophysiological tests has shown that peripheral neuropathy is prevalent amongst men with impotence. With reference to this information, it is advised that medical practitioners’ should perform neurophysiological examinations on erectile dysfunction patients and establish that the pelvic area has been screened effectively.

http://www.uk-med.co.uk/Health/Neuropathic-Pain-Connection-With-Erectile-Dysfunction

Coral Compound may help with Neuropathic pain

Today's post from esciencenews.com (see link below) is one of those where we have to ask the reader if they know anything more than is told here. It was published in 2009, so one assumes that some progress has been made in the development of a Capnellene compound as a pain relieving drug. It certainly sounds interesting.

Neuropathic pain: The sea provides a new hope of relief
Published: Tuesday, August 4, 2009 - 19:09 in Health & Medicine

A compound initially isolated from a soft coral (Capnella imbricata) collected at Green Island off Taiwan, could lead scientists to develop a new set of treatments for neuropathic pain – chronic pain that sometimes follows damage to the nervous system. Currently this form of pain is very poorly controlled by the usual analgesics (aspirin like drugs (NSAIDS) or even opioids like morphine) and novel treatments are urgently required. The conclusion of a paper published today in the British Journal of Pharmacology is that this new compound could be a candidate. Recent research suggests inflammation in the nervous system is a major causative factor for this condition. Inflammation activates supporting cells, such as microglia and astrocytes, that surround the nerve cells. These activated cells release compounds called cytokines that can excite nerves carrying pain sensation (nociceptive pathways) and cause the person to experience mildly uncomfortable stimuli as very painful (hyperalgesia), or stimuli that would normally induce no discomfort at all as painful (allodynia). Thus, cold drafts or lightly brushing the skin can produce intense pain, severely affecting the person's quality of life.

The treatments that give some relief to some patients are a very mixed bunch, nearly all found empirically and with many other effects. Amitriptyline, an anti depressant now used for urinary incontinence, has given relief in neuropathic pain; similarly, two drugs designed for treating epilepsy - gabapentin and pentagabalin have also proved effective for some sufferers. However, many patients do not respond to these currently available drugs.

"New, effective and safe painkillers are urgently needed for patients with neuropathic pain," says Dr Zhi-Hong Wen, who played a key role in a research study searching for novel compounds that have potential for use in pain relief. Dr Wen and colleagues work at the Department of Marine Biotechnology and Resources, National Sun Yat-Sen University, Taiwan.

Although the chemical they studied, capnellene, was originally isolated in 1974, it is only recently that scientists have started to appreciate its potential. Capnellene is interesting because its structure is very different from pain-relieving drugs currently in use. Initial experiments suggested that it may have pain-relieving properties. Working with Yen-Hsuan Jean MD, PhD and other colleagues, Dr Wen tested capnellene and a second very similar compound, in isolated microglial cells and in experimental models of the condition in rats.

They found that the compounds significantly reduced pain-related activities in isolated microglia, and that these compounds also significantly reversed hyperalgesic behaviour in the experimental rats.

"To provide better quality of life, we need new drugs that can act rapidly and have specific functions with low side effects. Moreover, we need better management for chronic pain conditions," says Dr Wen.

"Today there are few pharmacological agents that can help people suffering from neuropathic pain, but we believe that these marine-derived compounds could lead to the development of a new range of drugs of great potential," he adds.

http://esciencenews.com/articles/2009/08/04/neuropathic.pain.the.sea.provides.a.new.hope.relief

Neuropathic Pain Relief With PAP Injections

This fascinating article from sciencedaily.com (see link below) looks at the potential of  so-called PAP injections to relieve pain. You'll need to read it to find out what that is.  Many people try acupuncture in a bid  to help reduce their neuropathy symptoms. Some achieve some success and others none at all. The fact that acupuncture body maps are being studied by the University of North Carolina, with a view to injecting a protein at those points to achieve long-lasting pain relief, is very interesting, especially for those who have long had faith in aspects of ancient Chinese medicine.
 Neuropathy is that sort of disease and people respond differently to every form of medication or treatment, which of course makes it very difficult indeed to treat. Those who suffer from a lot of pain and may be on or approaching morphine treatment, may well find this article very interesting for the future. You may not understand everything here but you'll get the general idea.

Pain Relief With PAP Injections May Last 100 Times Longer Than a Traditional Acupuncture Treatment

ScienceDaily (Apr. 23, 2012)

Scientists at the University of North Carolina at Chapel Hill have identified a new way to deliver long-lasting pain relief through an ancient medical practice.

In an article published in the April 23 online edition of Molecular Pain, UNC researchers describe how exploiting the molecular mechanism behind acupuncture resulted in six-day pain relief in animal models. They call this new therapeutic approach PAPupuncture.

Principal investigator Mark J. Zylka, PhD, associate professor in the Department of Cell and Molecular Physiology and the UNC Neuroscience Center, said this is a promising study that moves his lab's work with prostatic acid phosphatase, known as PAP, towards translational research.

Several years ago, Zylka and members of his lab documented how injecting PAP into the spine eased chronic pain for up to three days in rodents. The only problem was PAP's delivery.

"Spinal injections are invasive and must be performed in a clinical setting, and hence are typically reserved for patients with excruciating pain," said Zylka. Though he had never received acupuncture or researched traditional Chinese medicine, Zylka said recent research showing how acupuncture relieved pain caught his eye.

"When an acupuncture needle is inserted into an acupuncture point and stimulated, nucleotides are released. These nucleotides are then converted into adenosine," said Zylka. Adenosine has antinociceptive properties, meaning adenosine can decrease the body's sensitivity to pain. The release of adenosine offers pain relief, but for most acupuncture patients that relief typically lasts for a few hours.

"We knew that PAP makes adenosine and lasts for days following spinal injection, so we wondered what would happen if we injected PAP into an acupuncture point?" Zylka said. "Can we mimic the pain relief that occurs with acupuncture, but have it last longer?"

To find out, Zylka and his lab injected PAP into the popliteal fossa, the soft tissue area behind the knee. This also happens to be the location of the Weizhong acupuncture point. Remarkably, they saw that pain relief lasted 100 times longer than a traditional acupuncture treatment. What's more, by avoiding the spine the researchers could increase the dose of PAP. A single injection was also effective at reducing symptoms associated with inflammatory pain and neuropathic pain.

"Pinning down the mechanisms behind acupuncture, at least in animal models, was critical," said Zylka. "Once you know what chemicals are involved, you can exploit the mechanism, as we did in our study."

The next step for PAP will be refining the protein for use in human trials. UNC has licensed the use of PAP for pain treatment to Aerial BioPharma, a Morrisville, N.C.-based biopharmaceutical company.

Zylka said PAP could be applicable to any area where regional anesthesia is performed to treat pain. And PAP has the potential to last longer than a single injection of local anesthetic -- the class of drugs used in regional anesthesia.
"When it comes to pain management, there is a clear need for new approaches that last for longer periods of time," said Julie Hurt, PhD, a postdoctoral fellow in Zylka's lab.

Zylka co-authored the paper with Hurt. The research was undertaken at UNC and was supported by the National Institute of Neurological Disorders and Stroke, a component of the National Institutes of Health.
http://www.sciencedaily.com/releases/2012/04/120423103715.htm

Measuring Neuropathic Pain

Sometimes the subject of disagreement between patient and doctor, the way pain is measured is crucial to the way the specialists and doctors look at each individual case. Everyone reacts to pain differently and many people feel bad because they seemingly can't cope with their pain well enough. People will even try to hide the extent of their pain from their doctor, even in a test, for fear of being seen as 'weak'. The need for accurate testing seems therefore to be a no-brainer. The problem is that the tests for neuropathic pain levels are anything but accurate and generally based on the patient's own account of his/her situation. The patient and doctor then have to place that pain somewhere on a scale of severity and then it becomes very subjective and not really helpful.

Today's very interesting article is another from the website of the Chiari/Syringomyelia support group (see link below). While Chiari and Syringomyelia are specific neurological diseases, everything here relates directly to all forms of neuropathic pain. The question is, whether it's possible to create an accurate test for nerve pain! At best, those that exist give the doctor a better idea of what stage the disease is at but at worst, wrong conclusions can be drawn and the patient receives inappropriate treatment.

Measuring Pain, Disease, And Disability

Pain, disease, and disability; in a general sense we all know what these terms mean. Pain is what you feel when you're hurt or sick. Disease is a virus, disorder, or neurological condition. Disability is when something prevents you from doing what you should be able to do. Easy to define, right? In English, yes; but how do you define these things in such a way that they can be used effectively in medical research? Most of medical research is what is known as quantitative research, which means it uses numbers. In order to do quantitative studies involving pain, disability, and disease impact, these words need to be translated into numbers. In other words, an effective method of measuring - or testing for - items like pain and disability is required to produce useful, scientific research.
If you take a moment to think about the various types of tests there are in everyday life, it is mind-boggling. From the slew of standardized tests that our children take every year, to personality tests that many employers now require, to product safety tests, to the hundreds of medical tests, tests are everywhere. Given this, it is not surprising that an entire of science of testing has evolved. Some researchers specialize in the theory of test development and implementation. Out of this science has emerged a couple of key concepts for evaluating the usefulness of tests: reliability and validity.
Reliability refers to whether a test consistently produces the same results on the same subjects. In other words, if Joe takes an IQ test, his score shouldn't change depending on who administers the test. A blood test is reliable if it gives the same - or very close - results when run several times on the same sample. Reliability is an important measure of a test, because if test results vary because a machine is inconsistent or the test is administered by different people, the test results are not very useful.
Validity refers to whether a test measures what it is supposed to measure. Validity can be harder to determine than reliability and is often the subject of controversy. One of the most controversial tests of all time is the IQ test. The controversy surrounds it's validity. Does the IQ test really measure intelligence? Some would argue it does, many would argue it doesn't. When dealing with issues like pain and disability, determining a test's validity can be challenging. Often a patient's view of disability and disease impact differs sharply from a doctor's and people experience pain differently. One way to determine a test's validity is to compare it's results to another measure. For example, a new pain measure might be compared to existing pain measures, or the results for a test of how outgoing someone is would be expected to be inversely related to a test for how introverted someone is.
While there are a number of tests that have been developed to measure pain, disability, and disease impact, it is important to realize that every test has it's strengths, weaknesses, and limitations. Just as scientific research must undergo peer review before publication, we as patients should examine research results through a skeptical filter and decide for ourselves whether the tools used in the study were reliable and valid enough to apply to us.
Following is a very brief overview of three scales: the Karnofsky Performance Scale, the McGill Pain Questionnaire (MPQ), and the SF-36 Health Survey. These assessments are by no means the only ones used to measure pain, disease, and disability; but they are illustrative of the importance of understanding a test when evaluating the results it produced. These tests were selected because they have been used in research reviewed by this publication relevant to the Chiari and syringomyelia community.

Karnofsky Performance Index (KPI)

The Scale

Health care professional assigns patient a score along 11 descriptions. Most relevant criteria are selected. Overall score ranges from 0 (Dead) to 100 (Normal):
100 - Normal, no complaints, no evidence of disease
70 - Requires occasional assistance from others but able to care for most needs
40 - Disabled, requires special care and assistance
10 - Dying, near death
0 - Dead

In use for many years, by many types of medical professional
Not designed as a quality of life measure, but most often used as such
Originally designed to assess nursing work loads (how much help each patient needed from a nurse)

Strengths

- Widely used and recognized

- Research shows valid measure of physical functioning

- Predictive value in cancer and transplant survival

- Quick and easy to use and administer

Weaknesses

- Very crude measure

- Relies solely on doctor assessment, yet research shows there is a marked difference between patient and doctor assessments on quality of life

- Narrow focus on the physical aspects of quality of life

- Overemphasizes mobility and assumes mobility leads to a higher quality of life

- Numeric scale has not been adequately tested given the measure's wide adoption

- Some research suggests the scale is not very reliable

Conclusion

The Karnofsky Performance Index appears to be a valid measure of physical functioning but there is no good basis for it's use as a measure of overall quality of life. It is very crude and relies solely on physician assessment and does not take into account social support, psychological well-being, and a patient's own point of view. When used with other quality of life measures, the KPI may be beneficial, but unfortunately this measure is often the sole one used in studies of Chiari and syringomyelia.

McGill Pain Questionnaire

The Scale

One of - if not the most - widely used measure of chronic pain
Developed by Melzack at McGill University, Canada
Uses 78 pain adjectives (throbbing, beating, pounding, e.g.) organized in 20 groups
Subjects select words that describe their pain
A group of doctors, patients, and students assigned numerical values to each word in developing the test
Results are based on a Pain Rating Index (uses the assigned numerical values), number of words chosen, and Present Pain Intensity (1-5)

Strengths

- Can be self-administered or by an interviewer

- Effectively quantifies pain

- Research shows the measure can differentiate between diagnostic groups of patients

- Research shows validity when compared to simple one-number pain scales

- Short version is available

- Has been widely used for many years

Weaknesses

-Takes 15-20 minutes to complete (repeat tests take only 5-10 minutes)

- Person must be familiar with the words being used

- Pain descriptors may not adequately cover words often used by people with joint pain

- Limited data on reliability

Conclusion

While acute pain can be quickly and easily measured using a one number scale (0-100), chronic pain can take many forms. The MPQ has shown over the years to be probably the best available scale for measuring chronic pain.

SF-36 Health Survey
The Scale

36 question survey used to assess general health status
Answers to each question contribute to score along one of 8 sub-scales: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional, Mental Health
Two summary measures are available based on sub-scales: Physical Health and Mental Health
Most questions have been in use since the 70's and 80's
8 sub-scales represent the most frequently measured concepts in widely used health surveys

Disease impact scores can be measured by subtracting "normal" scores for a population from the respondent's actual score

Strengths

- Can be self-administered or given by an interviewer or computer

- Widely used in many countries for many purposes

- Fairly strong reliability and validity data

- If norms are established can assess disease impact

Weaknesses

- Generic type health survey, not specific to a disease

- Does not try to measure items such as sleep, cognitive functioning, sexual functioning, family functioning, eating, recreation, and other common measures

- Does not measure symptoms or problems specific to a disease

- Norms must be established (data gathered from a large group of people) to assess impact

Conclusion

Widely used, the SF-36 is a solid, respected general health survey. But because of it's generic nature, it may miss issues critical to patients of a specific disease.

As the descriptions above demonstrate, there are many scales to measure pain, disease, and disability. Each scale has it's own strengths and weaknesses and like any tool, it's effectiveness is determined largely by how it is used and who is using it. Ideally, a scale specific to the symptoms, treatments, and neurological deficits of Chiari and syringomyelia patients should be developed. The development of such a scale would benefit research into surgical (and non-surgical) treatments and provide a tool to measure how much an individual is being affected by their condition.
Until such a measure is developed, it is important to keep in mind the limitations of what is being used today.

http://www.conquerchiari.org/subs%20only/Volume%202/Issue%202(1)/SR%20-%20Measuring%20Pain,%20Disease,%20Disability.asp

A Holistic Approach To Emotions And Neuropathic Pain

Today's post from blog.aapainmanage.org (see link below) is an interesting one for neuropathy sufferers because it addresses the effects emotional response can have on your pain. It's written from the point of view of a holistic doctor with special emphasis on traditional Chinese medicine. I would personally argue that neuropathic pain is so specifically 'different' that your emotional state has little effect on the strength of your pain. However, it's undoubtedly true that the better you feel, the better you are able to deal with neuropathic symptoms. The question is: is it a chicken and egg situation where the pain causes the emotion and not the other way around? Worth a read to see where your situation fits on the grid.

How Emotion Can Relate to Location of Pain
By Jennifer Johnston, PhD, DNM, NMD Posted by The Academy, Jun 29, 2016,

Research is well established on the influence of emotions on perception of pain, pain treatment, catastrophizing, and speed of healing. The Institute of Medicine reports, “people’s experience of pain can be influenced by genes, cultural attitudes toward hardships, stress, depression, ability to understand health information, and other behavioral, cultural, and emotional factors. Successful treatment, management, and prevention of pain require an integrated approach that responds to all the factors that influence pain” (1).

Emotions of stress, joy, sadness, or even anxiety are all a natural part of life and are often felt physically. When preparing to step on the stage to give an important speech we may feel our anxiety as a physical sensation of knocking knees or even butterflies in the stomach. When meeting to go on a first date we may experience anxious feelings as a flutter in the chest, swirling feeling in the head, or nervous smile. Each of us may describe how we experience a situation differently, but most agree on how basic feelings are experienced in the body.

When emotions become excessive, suppressed, or turned inward they may begin to influence our overall physical function and how and where we perceive pain. Studies have established that emotions have distinct biological expressions that influence overall health. Additionally, emotions are responsible for prompting the body to prepare us to react to environmental challenges by communicating with the cardiovascular, skeletomuscular, neuroendocrine, and autonomic nervous system. For example, stress can both be the cause and influencing factor for a variety of physiological responses that can enhance health or promote disease (2). When we sense fear our flight or fight responses are activated and we feel that fear in the body. By taking a deeper look at how emotions correlate with the location of pain we may find a deeper understanding on why and how patients experience pain.

Body Mapping

In 2014 researchers were able to identify locations of body sensations related to emotions using a topographical body mapping method. Results reveal consistent and distinct maps associated with basic emotions. Physical sensory information is known to trigger conscious emotional experiences. This study showed that different emotional states are associated with distinct and culturally universal body regions. These regions could aid in our understanding of how emotions correspond with pain locations in the body (See figure 1, below) (3).



Researchers ran five studies with a total of 701 participants and identified that different emotions were reliably associated with statistically identifiable bodily sensation. These maps were equal among both West European and East Asian samples. They propose that emotions are represented in the somatosensory system as culturally universal categorical somatotopic maps (3).

TCM: Emotions and Meridians

Traditional Chinese Medicine (TCM) views the body as a whole, with mind, body, and emotions as correlated factors influencing overall health and happiness. A TCM fundamental principle states that everything experienced on the outside of the body reflects the quality of health on the inside (4). Certain areas of the body are more vulnerable to injury due to potential underlying emotion, energy, or organ imbalance. Many individuals experience a physical event, such as a slip or fall, so why do some experience injury and others do not? Why do some individuals experience injuries to their knee, ankle, hip, low back, or wrist? Why is there so much variation in the potential for injury and the location of the injury?

Sports Medicine Journal reported that 1.5 million young men participate in football and an estimated 1.2 million football-related injuries are reported annually. Overall, 50% of all injuries were lower extremity injuries (with knee injuries accounting for up to 36%). Thirty percent of injuries occurred in the upper extremities. Overall, sprains and strains accounted for 40% of injuries, contusions 25%, fractures 10%, concussions 5%, and dislocations 15% (5).

Pain can result from an external source, such as an auto or sports injury that damages the meridians and physical structure, as well as from an internal condition, such as an organ or energy imbalance. It is often easier for the practitioner to identify and treat the cause when it is related to external visible factors. Pain related to internal or emotional conditions has a tendency to be more complex, and effective treatment requires a closer look to determine the root cause.

All emotions can influence the body’s response to external factors such as injuries and accidents. It is when emotions become out-of-balance, excessive, or repressed that overall health and pain responses are influenced. Excessive or repressed emotions are understood to contribute to organ imbalance thereby leaving the body more susceptible to physical damage, pain, and injury.

The reverse is also true. Individual organ health can similarly influence the experience of emotions and pain. The theory is that balancing the organ that is associated with the emotion results in a balancing of the associated emotion. Sometimes the organ is out of balance and produces the emotional imbalance or potential physical vulnerability for injury. The difference is important to the practitioner in identifying and reducing future recurrence of the symptom.

Meridians are a three-dimensional energy network in the body that make pathways that connect to each other and to every bone, tendon, tissue, organ, and skin cell. These intercommunication networks function within the entire physical and emotional framework. There are 12 major meridians that run through the body (4). The left and right sides of the body mirror each other, while the back and front are different. Each meridian corresponds to an internal organ along with the associated emotions and other similar energy frequencies. (See Figure 2, below).



Liver and Gallbladder. An individual experiencing feelings of anger, frustration, irritability, and stress may be suffering from a liver imbalance. Liver and gallbladder meridians are correlated with migraine headache, tendon and ligament problems, ankle and hip pain, menstrual cramps, and arthritis. When the liver becomes healthier, the associated physical pain and emotion will reduce or disappear. However, a persistent lifestyle situation that increases or continues feelings of stress and anger will cause the liver imbalance to continue, along with the associated pain (4).

Spleen and Stomach. The spleen and stomach are associated with feelings of worry and over-thinking. Imbalances in these meridians can result in excessive or easy bruising, muscle injuries, or pain conditions related to the torso, front of the legs, and feet. Pain felt in the big toe can be linked to digestive imbalances involving the liver and spleen, as both meridians end in the big toe (4).

Kidney and Bladder. The kidney and bladder are associated with the emotions of fear and anxiety and their meridians are further related to pain associated with the knee, heel, neck, low back, feet, and bones. In a case study involving kidney function and meridian location, a female reported sore knees after skiing season and a subsequent right knee injury resulting from skiing (6). In this case, the sore and injured knees are related to the activity of skiing but, why the knees and not the hips or ankles? TCM theory links the state of the individual’s kidney energy and function to the health and resilience of the knee area (4).

Lung and Large Intestine. The lung and large intestine are associated with the emotions of sadness, depression, and grief. Pain conditions correlated with these organs and their meridian locations include painful skin conditions and shoulder, elbow, and hand injuries (4).

Heart and Small Intestine. The heart and the small intestine are related to the emotions of joy and happiness and are further associated with pain experienced in the upper body, chest, shoulders, and hands.

For instance, a broken heart from a problematic relationship will eventually cause an organ function disorder if the emotion is not addressed and resolved. Joy is the heart’s corresponding emotion. When an individual loses the capacity to experience joy, the heart’s health can be negatively affected resulting in both physical and emotional pain (4).

Due to the complexity of pain and emotions, the diagnostic process should include many questions related to lifestyle, emotional wellbeing, and physical health to aid in identifying the root cause of the pain. Our job as practitioners is to help patients evaluate all contributing factors related to their pain condition, not just the physical. Once the key underlying cause is identified, then the imbalance can be addressed and the environment that created that imbalance can be changed.

Additionally, when considering emotional correlates to pain it is important to remember that cause and effect are not linear but circular. For example, after an auto accident we can say that the accident caused a neck injury, but why the neck location for that individual? The sore neck is the symptom of the effect of the auto accident which is the cause. But what set the stage for the injury in the first place?

Pain can be a complex symptom and the cause may not be so straightforward, which is especially true when dealing with emotional factors. Which preexisting emotional patterns or organ imbalances have contributed to the individual’s specific pain symptoms and locations? We have the opportunity as practitioners to identify underlying factors that contribute to pain in order to help patients relieve and/or reduce the manifestation of pain.

Finding the time to help our patients identify emotional and lifestyle factors related to pain symptoms can be challenging. It is also important to take the time to examine and identify how our own personal choices influence our physical and emotional experiences. Finding time to relax, take a nap, or have some much needed fun is always a good first step toward improved health and happiness.

Jennifer Johnston, PhD, NMD, MS, is a board-certified practitioner at Holistic Health Solutions, Inc. with more than 13 years’ experience in naturopathic and Traditional Chinese medicines. She has a master’s of science with studies in psychoneuroendocrinology and a doctorate in clinical nutrition. Dr. Johnston is part of TCM World Foundation’s advanced studies program and is certified to practice LifeForce: Tao of Medical Qigong, Dragon’s Way®, Menopause and Breast Health programs.

References
Institute of Medicine (US) Committee on Advancing Pain Research, Care, and Education. Relieving Pain in America: A Blueprint for Transforming Prevention, Care, Education, and Research. Washington (DC): National Academies Press (US); 2011.
Institute of Medicine (US) Committee on Health and Behavior: Research, Practice, and Policy. Health and Behavior: The Interplay of Biological, Behavioral, and Societal Influences. Washington, DC: National Academies Press (US); 2001.
Nummenmaa L, Glerean E, Hari R, Hietanen JK. Proc Natl Acad Sci USA. 2014;111(2):646–651.
Nan L, Schaplowsky E. Traditional Chinese Medicine: A Natural Guide to Weight Loss That Lasts. New York, NY; TCM World Foundation; 2000: 139-142, 159-161, 180, 200-203, 218-223.
Saal JA. Common American football injuries. Sports Med. 1991;12(2):132-147.
Nan L. Ask Dr. Lu: Volume One. New York, NY: TCM World Foundation; 2011: 97-99 & 121-122.

From The Pain Practitioner, Fall 2015 issue. Join the Academy to receive The Pain Practitioner.

http://blog.aapainmanage.org/emotion-can-relate-location-pain/

A Neuropathic Pet Is Also For Life And Not Just For Christmas

Today's post from petmd.com (see link below) highlights a little-known fact that dogs, cats and other domestic mammals can also suffer from neuropathy. Now if you suffer from nerve damage, you can tell others how you're feeling but even then, it can be difficult describing your symptoms. Imagine then how long a dog or cat might be suffering before you notice something's wrong! They can't tell you and you can't question them! This article provides a list of symptoms to look out for, which is helpful. It's also pretty astonishing to learn that one of the common treatments is Gabapentin, which as you know is also prescribed for humans (with or without side effects). Spare a thought for your pets this festive season - they don't have special orthopedic footware as they walk through the mud and cold but you can imagine what they may be going through if they suffer from neuropathy. If you're concerned, a trip to the vet may be in order.

Neuropathic Pain in Dogs 
Pain from the Nervous System in Dogs

Neuropathic pain commonly results from an injury or disease relating to the body’s nerves and how they function, or within the spinal cord itself. This particular kind of pain is difficult to pinpoint, especially in patients that are unable to respond to specific inducements.

Symptoms and Types

Damage to the tissues of the body, and the nerves running through them, creates a constant (chronic) pain that is brought on by a light touch to the affected area and/or a heightened perception of pain. Pain originating within the spinal cord causes problems with mobility and various functions of the body.

Some of the symptoms of neuropathic pain may include:

Limping or dragging a limb
Shaking or twitching of the skin
Chewing on the affected area
Muscle wasting (atrophy)
Crying out (vocalizing)
Decreased appetite
Urinating and defecating inappropriately (incontinence)

Causes

Neuropathic pain may result from an injury to body tissues or a growth (tumor) in the spinal cord. Diseases that affect the spinal cord, such as intervertebral disc disease (IVDD), may cause pain in different areas of the body, depending on which part of the cord is affected. Another potential cause of neuropathic pain is amputation of a limb. Phantom limb pain results in the impression of pain coming from a leg that has been surgically removed.

Diagnosis

In general, neuropathic pain is diagnosed by ruling out other causes of pain and performing reflex tests to evaluate the nervous system. Basic blood tests can help rule out infectious and disease-related causes. X-rays and special imaging may be necessary to search for tumors in the bone or spinal cord. Finally, a good discussion of your dog's medical history and previous symptoms will help lead to the proper diagnosis.

Treatment
Analgesic medications (those that relieve pain) are used as the initial treatment for neuropathic pain. The amount given may need to be changed until the best effect is achieved. Other types of pain relievers may be tried until the one that works best for your dog is found. Some veterinarians may choose to use several pain medications at one time and then taper off until only one is being given.

One medication that has been used with success for long-term pain is gabapentin. This anti-seizure drug has analgesic properties that are particularly effective for reducing neuropathic pain in dogs. Gabapentin is given once daily for pain control and can be given with or without food. The particular side effects of this drug include sedation, weight gain and stumbling (ataxia). Diarrhea may also be seen in some animals.

Living and Management

Dogs with chronic pain may gain considerable relief from analgesic medications. The quality of life for these animals can be much improved, as long as the underlying condition causing the pain is under control.

In dogs with kidney problems, the dosage of gabapentin may be reduced, as the drug is processed through the kidneys and they must be functioning properly for the drug to be removed from the body. Animals that are pregnant should not be treated with gabapentin. When discontinuing the medication, gabapentin should be slowly tapered off to prevent seizures from occurring after long-term use.

http://www.petmd.com/dog/conditions/neurological/c_dg_neuropathic_pain

Chronic Neuropathic Foot Pain Vid

Today's post from dontpunishpain.com (see link below) is a short but graphic video designed to let people know how awful neuropathic foot pain can be. It's a tad over-dramatic but it's easy to see where he's coming from and why he presents it this way. The lack of public awareness of neuropathy means that sometimes we have to use dramatic methods to get people's attention and this short video does just that. It is important to know that you can suffer chronic foot pain from neuropathy without the sores shown in the image on the video and that that image is an extreme example but nevertheless the message of the video is entirely correct.

Feel This Pain: Peripheral Neuropathy - Crippling Foot Pain 

Ken McKim Published on 5 Jul 2014

Episode 3 of the "Feel This Pain" series, where I attempt to convey what it is like to suffer with the debilitating foot pain that comes with Peripheral Neuropathy, yet another so-called "invisible illness."


 http://www.dontpunishpain.com/journal/2014/7/5/feel-this-pain-peripheral-neuropathy-crippling-foot-pain

Neuropathic Pain Memories in the Spine

Today's interesting post from Discover Magazine (see link below) follows on from the post of a few days ago about opioids having the ability to remove the 'memories' of pain. A reader asked if there was more information on this subject and this article written by British science writer, Ed Yong shows how pain memories are stored in the spine and are subject to the workings of certain molecules. It may appear heavy going if you're reading this on the train on your way to work but it's written very clearly and certainly inspires hope for the future for long-term neuropathy sufferers.

A Memory for Pain, Stored in the Spine
Ed Yong, May 2011

You slam your hand in a door, and the experience becomes etched into your brain. You carry a memory of the swinging panel, the sound as it crushes your flesh and the shooting pain as your skin gives way. Your body remembers it too. For days afterwards, the neurons in your spine carry pain signals more easily form your hand to your brain. As a result, your hand feels more sensitive, and even the lightest touch will trigger an unpleasant reaction. It’s as if your spine carries a memory for pain.

This is more than a metaphor. Two groups of scientists have found that one special molecule underlies both processes. It helps to store memories in our brains, and it sensitises neurons in our spines after a painful experience. It’s a protein called PKMzeta. It’s the engine of memory.

When we learn new things, PKMzeta shows up at the gaps between neurons (synapses) and strengthens the connections between them. These bolstered synapses are the physical embodiment of our memories, and they are fragile things. It turns out that we need to continually recreate PKMzeta at synapses to keep our memories alive. If the protein disappears, so do our memories. Unlike the text of a book or the bytes of a hard disk, the information stored in our brain is constantly on the verge of being erased.

This has to be one of the most surprising discoveries of modern brain science, and it’s the handiwork of Todd Sacktor. In 2006, his team managed to erase memories in the brains of rats with a chemical called ZIP, which neutralises PKMzeta. Even very strong memories, which has been around for months, vanished irreversibly. This year, Sacktor did the opposite – he boosted old, faded memories in rats by giving them extra PKMzeta.

Now, Marina Asiedu and Dipti Tillu from the University of Arizona College of Medicine have shown that PKMzeta does more than stabilise memories in the brain. It’s also behind the lingering pain we feel after an injury.

Asiedu and Tillu knew that after a painful experience, neurons that carry pain signals develop stronger connections, especially those in a part of the spine called the dorsal horn. This is the same thing that happens in the brain when we learn something new, and the duo reasoned that PKMzeta might be involved in both processes.

To test their idea, Asiedu and Tillu injected mice in the foot with a chemical called IL-6 that triggered a mild swelling and made the limb more sensitive for up to three days. It mimicked the feeling that you get after you catch your hand in a door, without actually injuring the animals. Even after the swelling goes away, the paw remains sensitive – the ‘primed’ mice will react to a second chemical called PGE2 that wouldn’t normally bother them.

None of this happened if Asiedu and Tillu used ZIP (the anti-PKMzeta chemical). If they injected the mice with ZIP and IL-6 at the same time, their feet never became more sensitive. Without PKMzeta, they couldn’t develop a memory for the pain. Even if ZIP followed IL-6 by three days, it erased the sensitivity in the rodents’ paws – the treated mice didn’t react to a shot of PGE2. And when Asiedu and Tillu loaded the mice with a protein that mimics PKMzeta, their sensitive streaks returned.

These fresh results tally with those from another study by Korean scientists Xiang-Yao Li, Hyoung-Gon Ko and Tao Chen, which was published last year. They found that PKMzeta is also involved in a different type of chronic pain, caused by more severe damage to nerves around the body. Following this sort of damage, the PKMzeta memory engine starts chugging away in a part of the brain called the anterior cingulate cortex (ACC), leading to consistent and long-lasting pain. An injection of ZIP erased this pain, at least for a few hours.

The two studies have important differences that will need to be unpicked. Why, for example, did Asiedu and Tillu’s manage to erase the “pain memories” in the long-term, while the Korean team only did so for a few hours? Why was the hotspot of PKMzeta activity located in the spine in one study but the brain in another?

The answers to these questions could tell us a lot about the differences between different types of pain. But on the whole, the experiments build a compelling picture of PKMzeta accumulating in neurons after an injury, and priming them for persistent pain.

If the same thing happens in humans, then it might be possible to treat long-lasting pain with drugs that target PKMzeta. This is no trivial matter. A Europe-wide survey found that around one in five adults had suffered pain for more than 6 months. Around half of these people felt their pain constantly, and half had suffered for 2 to 15 years. They continue to suffer because we still know very little about the molecules responsible for this most primal of feelings. With PKMzeta, we’re one step closer to some answers.

******

Footnote: This study has a special significance for me, because it was partially inspired by this blog.

A couple of years ago, I wrote a feature for the Times about memories, and I interviewed Sacktor for the piece. As per usual, only a few select quotes made it into the article. But, as I often do, I posted the full transcript of the interview on this blog. In one of his replies, Sacktor suggested that PKMzeta might be involved in pain memory. He said, “There’s also a condition called central neuropathic pain syndrome, where people catch their finger in the car door and even after the injury heals, a memory for the pain is set up in the central nervous system. ZIP could erase that too.”

Theodore Price, the lead scientist behind Asiedu and Tillu’s piece (who blogs as Juniorprof), read the interview and was intrigued. He said to me, “His comment in your interview influenced me greatly and led to some of the experimental design we used in this paper. It was a total eureka moment for me.”

Sacktor is also pleased, especially since PKMzeta, seems to have roles in pain, addiction, post-traumatic stress and more. During his teenage years, Sacktor would argue with his father – a biochemist – about the best way to tackle diseases. His dad would argue that you need to understand the underlying biology first. Sacktor preferred tackling the disease directly. “I realized long ago my Dad was right,” he says. “The possibility that my father was more right and I was more wrong than I could have known, brings me more happiness than I could have imagined.”

Things have, in a way, come full circle – science inspires blog post, which inspires more science, which inspires a new blog post. It’s worth noting that the key quote from Sacktor never made it into the Times piece. Without that transcript, this new paper wouldn’t exist.

http://blogs.discovermagazine.com/notrocketscience/2011/05/11/a-memory-for-pain-stored-in-the-spine/