Neuropathic Pain For Health Professionals

Today's post from journals.lww.com (see link below) written for Nursing magazine, is a comprehensive article about neuropathy, its causes and treatments for health professionals. It's often interesting to read about how professionals are taught to approach the disease. We can then better understand the reasons for their decisions on our behalf. It also can give us some insights that the doctors don't tell us, either because they don't have time, or because they consider the subject matter too complex for the patient to understand. Definitely worth a read on a day when you don't have to rush off to work. The reference links referred to by the numbers throughout the article can be followed in the original article (see link below).

Living with the nightmare of neuropathic pain
D'Arcy, Yvonne MS, CRNP, CNS Nursing 2014

PATIENTS LIVING WITH a neuropathic pain syndrome will tell you that this vicious pain can ruin quality of life and spoil dreams. Some neuropathic pain, such as that from diabetic neuropathy, has a gradual onset, but other types, such as complex regional pain syndrome (CRPS), can develop suddenly. Some patients with neuropathic pain who have difficulty getting a diagnosis can experience increased pain and anxiety from the uncertainty of their pain condition.

To get a better understanding of this pain, let's look at a patient who had an accident that resulted in a neuropathic pain syndrome that changed her life.
 
Meet the patient

Mrs. S, age 65, is a retired teacher who went to bed one night free from pain. During the night, she got up to use the bathroom without turning on the light and ran into a table leg quite hard, injuring her right foot. Because the pain was so severe, her husband drove her to the ED. There she rated her pain as an 8 on a pain intensity rating scale of 0 (no pain) to 10 (worst pain imaginable).

The healthcare provider (HCP) obtained an X-ray of her foot, which revealed no fractures. Believing that Mrs. S had only soft-tissue damage, the HCP prescribed an opioid-acetaminophen combination medication for moderate pain, and told her to elevate, ice, and rest her foot for several days.

Although Mrs. S very diligently rested her foot, used ice packs, and took her medications as needed, the pain didn't resolve. In fact, it increased and became constant. Over the next 6 weeks, Mrs. S was evaluated by many HCPs, but none could give her a concrete diagnosis. Her pain was 7/10 at best and none of the pain medications she'd been given significantly relieved it; instead, they just made her sleepy. Because she had trouble putting weight on her foot, she started to use crutches. Her foot often felt cold, so she tried to put a sock on for warmth, but she couldn't stand the pressure it put on her foot.

Her husband was concerned about her unrelieved pain, loss of function, and lack of sleep due to pain. At 3 months, Mrs. S was referred to the local pain management specialist, who diagnosed her with CRPS, a neuropathic pain syndrome where the injury is located in the peripheral nerves but can also include changes in the central nervous system.1 (See Focusing on CRPS.)

When Mrs. S asked about treatment, she was told the pain would most likely persist and that the best approach was to try medications designed to treat neuropathic pain to help reduce it. At this point, she broke into tears and told the specialist, “This can't be! I just retired after teaching for 30 years. I planned to travel the world and now I'm in constant pain. How could this have happened to me?”

What we know about neuropathic pain

Neuropathic pain is chronic pain caused by damage in the peripheral or central nervous system. It's been defined as pain that's the direct consequence of a lesion or disease affecting the somatosensory system.2 (See The language of pain.)

This distinct type of pain encompasses a wide variety of neuropathic pain conditions. Unlike acute pain, it has absolutely no protective function and doesn't require any nociceptive input; that is, it exists independent of a stimulus. In contrast, nociceptive pain results from damage to tissue that's nonneural, such as surgical tissue damage or a tissue injury. Nociceptive pain is caused by activation of thermoreceptors, chemoreceptors, and mechanoreceptors, depending on whether the pain is caused by burns or muscle or tendon damage.3

Clinically, a patient such as Mrs. S doesn't have to move or walk on her affected foot to have pain. This type of pain persists without any pressure or sensory input.

Sorting out neuropathic pain

Of the many different types of neuropathic pain, some are caused by chronic diseases such as diabetes or HIV infection. Others, such as postmastectomy pain syndrome, result from surgery or treatments such as chemotherapy. Overall, neuropathic pain is thought to affect 1,765,000 people in the United States, not including those with back pain neuropathy.4 (See Sorting out common neuropathic pain conditions.)

Neuropathic pain has many sources and causes. For example, the continued inflammatory process of osteoarthritis may create neuropathic pain. Fibromyalgia is now considered a disease caused by dysregulation of pain inhibition pathways and amplification of central pain.5
 
Pathophysiology: Getting to the root

Generation of neuropathic pain involves both the peripheral nervous system and the central nervous system, and both the ascending and descending neural pathways. It's maladaptive: Neuropathic pain promotes abnormal functioning of nerves in one or both systems leading to a difficult-to-treat chronic pain condition.6 As the nerves change function, a phenomenon called neural plasticity occurs. These changes are responsible for heightened pain sensitivity and unpredictable, sudden pain exacerbations.

If the source of the neuropathic pain is in the periphery, continued pain stimuli from the peripheral nerve injury create sensitization that over time creates abnormal neural activity along the afferent nerve pathways leading to the central nervous system.7 This sensitization causes the release of what's commonly called an “inflammatory soup” of pain-promoting substances such as cytokines, tumor necrosis factors, bradykinin, and substance P. This in turn leads to hypersensitivity of the nerves, allowing them to crosstalk with each other, release pain-facilitating substances, activate higher level pain-generating functions such as N-methyl-D-aspartate receptors, and fire faster.

Sodium channels on nerve fibers play a part in the creation of neuropathic pain. In normal neural functioning, nerve depolarization occurs when the stimulus reaches the activation point and the nerve is forced to fire. When neuropathic pain is created, more primary and secondary sodium channels are activated, allowing for an ectopic neural discharge.4

Pain that originates from the central nervous system is even more difficult to manage. Pain that's centrally controlled can be created by a continued barrage of pain stimuli to the peripheral neurons, causing central neurons to become hyperexcitable. This hyperexcitability has been transferred to the central nervous system through the synaptic junction between the two nervous systems. As a result of this central sensitivity, synaptic connectivity reorganizes, causing lower activation thresholds and increased responses to stimuli.8

Additionally, collateral neurons may sprout and create larger fields of effect with the ability to crosstalk with each other and recruit additional neurons for pain creation. This phenomenon, called wind-up, causes an increased response to painful stimuli.6 Meanwhile, the descending pathway inhibition potential used to block pain is adversely affected, letting more pain reach the patient.

This explains the pain that Mrs. S is continuing to have. Continual pain stimuli from the periphery have created central sensitization and the wind-up effect has been created related to neuronal plasticity. Because the pain had continued at high levels for so long, the central nervous system pain-facilitating process was activated, which will make her pain much harder to manage.
 
Signs and symptoms

When assessing neuropathic pain, the nurse must ask the patient to describe the pain. Aside from the numeric pain intensity scale, the descriptors the patient uses are the best means of identifying the pain. If the patient uses words such as burning, shooting, electric, painful numbness, or tingling, the pain has a neuropathic source. After a mastectomy, some patients complain of strange painful sensations or painful pruritus in the ipsilateral axilla or upper arm. This is also classified as neuropathic pain.

Using fiber wisps for sensation testing or alcohol to create a cool sensation and touching the painful areas can determine just how large an area is affected. Ask patients if they experience hyperalgesia, increased pain from a stimulus that's normally painful, such as a pinprick, or allodynia, a painful response to a stimulus that isn't normally painful, such as touch from clothes or bedsheets.6 Assess for other signs of neuropathic pain. Other common types of neuropathic pain include paresthesia, an abnormal sensation that isn't unpleasant, such as numbness or tingling, and dysesthesia, an unpleasant sensation such as painful pruritus or feeling as though bugs are crawling under the skin.6

In the acute phase, patients who are developing CRPS after an injury continue to report high-intensity pain despite escalating doses of opioids. As the condition develops, besides allodynia, patients report edema, skin discoloration due to changes in blood flow, temperature differences between the affected and nonaffected extremity, changes in hair and nail growth, weakness, and tremor.9

Mrs. S is having difficulty with severe pain and she can't put any pressure on her foot. She has allodynia, and she's started to use descriptors indicative of CRPS, such as painful coldness.
 
Treatment options

One of the best ways to manage neuropathic pain is to use a stepwise approach. To adequately assess and diagnose a patient with neuropathic pain, the HCP will need to perform a focused physical exam. If possible, the HCP will identify the source, make a diagnosis, and examine any contributing comorbidities such as diabetes. Remember that the patient may not understand that pain descriptors may be the key to adequate management.

Besides explaining the diagnosis to the patient and discussing treatment options, the HCP will set realistic achievable goals. Many patients with neuropathic pain have seen multiple HCPs with no success; receiving a diagnosis may end the uncertainty that these patients have experienced and give them some hope for reducing the pain. Although complementary techniques such as relaxation or yoga may be beneficial for adjunct pain relief, the mainstay is pharmacologic management.

Stepping up to medications

Using the stepwise approach to treatment includes using first-line medications with the highest level of evidence for success in controlling neuropathic pain. (See Lining upmedications for neuropathic pain.)

After patients begin drug therapy, nurses need to reassess the efficacy of the therapeutic regimen. If the first medication chosen doesn't provide pain relief or increase functionality, the HCP may try titrating the dose upward. If that doesn't provide adequate pain relief, the HCP may consider combining two first-line medications.

If careful drug choices in the first-line category don't provide adequate pain relief, trialing second-line options may be a way of optimizing pain relief. As always, adding nonpharmacologic therapies, such as yoga, pool therapy, or meditation, can help with pain relief and relaxation.

For Mrs. S, our patient with CRPS, using one or more first-line therapies should provide some level of pain relief. Her current medication is an opioid, which is a second-line option. Using first-line medications either alone or in conjunction with the opioid may optimize her pain relief, and a consultation with physical medicine and rehabilitation professionals to work on increasing functionality is highly recommended. Mrs. S may never be pain free—that isn't a reasonable goal for her—but she should be able to move to a higher level of physical activity and perhaps begin to take short trips to see some of the places she's been dreaming about.

New options on the horizon

Research evidence supports the use of some antiepileptic drugs for certain types of neuropathic pain such as painful diabetic neuropathy. However, lacosamide, an antiepileptic drug, was trialed for managing neuropathic pain and fibromyalgia but failed to show significant benefit. The FDA has declined to approve its use for neuropathic pain.10 Another therapy that produced better outcomes is topical application of high-dose capsaicin, 8% patch, which is thought to produce desensitization. It's indicated for a particularly difficult-to-treat neuropathic pain syndrome called postherpetic neuralgia. In six studies involving 2,073 patients, a small number of participants with postherpetic neuralgia and HIV neuropathy with high pain levels benefited.11 Pain relief lasted for up to 12 weeks. In studies, 11 or 12 patients had to be treated to get 1 positive outcome of reduced pain (this is known as numbers needed to treat and is considered high).11 However, some patients did benefit, and their pain was significantly reduced.

Although single medications used alone can positively affect neuropathic pain, combination therapy demonstrates superior pain relief. Some agents caused problematic sedation.12 Unfortunately, there weren't enough comparative or replication studies to identify particular combinations of drugs that had improved pain relief. In a meta-analysis with 386 patients, gabapentin plus an opioid was superior to gabapentin alone, according to a modest but clinically significant finding.12

One of the most exciting ideas for managing neuropathic pain is attempting to use molecular approaches. Chromaffin cells release a combination of pain-reducing neuroactive compounds, including catecholamines and opioid peptides.13 Encapsulating the cells and implanting them in the subarachnoid space has relieved pain in both animal and human studies.13

In these cell transplantation studies, encapsulated cells with permeable membranes turn into cellular pumps that create and dispense analgesic compounds.13 Future research targets include astrocyte cells that are genetically modified to secrete enkephalin and genetically engineered cells designed to secrete gamma-aminobutyric acid, a pain inhibitory substance.13 Patients thought to be good candidates for study include those with low back pain and knee pain; these can have neuropathic elements. Understanding the pathways and physiology of neuropathic pain transmission can help researchers look for ways to use these specialized cells to reduce pain right at the source of pain generation.

Other options for managing neuropathic pain include using autologous bone marrow-derived progenitor cells to repair damaged neurons in patients with diabetic peripheral neuropathy and gene transplants applied to peripheral nerves, injected into dorsal root ganglia, or introduced into the intrathecal space of the spine via lumbar puncture or injected directly into the brain.13 Gene transplants have been tested only in animals using the herpes simplex virus.13

Stem cell transplantation also provides promise for pain research. Mesenchymal stem cells can be harvested from bone marrow, are fairly stable, and can, once transplanted, migrate to injured tissue and have immunosuppressive characteristics.14 They can also differentiate into astrocytes and neurons and migrate to injured neuronal areas to mediate functional recovery.14 Although many of the finer points of the process are yet to be discovered, studies of mice have shown that the transplanted stem cells relocated themselves into key areas for neuropathic pain generation in the brain.14

Although many new management options are still being studied in animals, they hold promise for human use in the future. Researchers are attacking the pain process from many different directions and using the known pain pathophysiology to direct the therapy to targets that may yield good results.

In the foreseeable future, patients like Mrs. S won't be limited to medications or interventions for intractable pain syndromes such as spinal cord stimulators. Instead, they'll have options that include stem cell transplants for nerve repair or genetically engineered cells that will enhance the production of pain-reducing substances. Using these new techniques will help many patients leave the nightmare of neuropathic pain behind and fulfill their dreams.

Focusing on CRPS

CRPS, or complex regional pain syndrome, was formerly called causalgia or reflex sympathetic dystrophy.3 It's usually the result of a crush injury or repeated tissue trauma. Continuing pain or abnormal sensation is out of proportion to the event that initiated it. At some time, the patient experiences edema, skin blood flow changes, or abnormal sudomotor activity in the region of pain. No other condition is identified that could explain the pain or dysfunction.15

The International Association for the Study of Pain defines two types of CRPS:

CRPS I, which doesn't require the presence of a nerve lesion.
CRPS II, which includes the presence of a nerve lesion.
Although the true cause of CRPS hasn't been determined, the most accepted rationales include the following:
enhanced peripheral neurogenic inflammation
sympathetic nervous system dysfunction
structural reorganization in the central nervous system.

Source: Fechir M, Geber C, Birklein F. Evolving understandings about complex regional pain syndrome and its treatment. Curr Pain Headache Rep. 2008;12(3):186–191.


The language of pain

Allodynia: painful response to a stimulus that isn't normally painful, such as touch from clothes or bed sheets.
Crosstalk: new communication, or neural sprouts, between nerves that don't normally synapse with one another.
Dysesthesia: an unpleasant sensation, such as painful pruritus or feeling as though bugs are crawling under the skin.
Hyperalgesia: increased pain from a stimulus that's normally painful.
Neural plasticity: continued noxious stimuli and inflammation causing an elevation of nociceptive input from the periphery to the central nervous system, which then creates an increased response at the cortical level to change its somatotopic organization for the painful site, inducing central sensitization.
Neuropathic pain: chronic pain caused by damage in the peripheral or central nervous system that's the direct consequence of a lesion or disease affecting the somatosensory system.
Nociceptive pain: pain that results from nonneural damage to tissue.
Paresthesia: an abnormal sensation that isn't unpleasant, such as numbness or tingling.
Wind-up: an increased response to painful stimuli. Add, on a new line as source format:

Source: Chou R, Fanciullo GJ, Fine PG, et al. Clinical guidelines for the use of chronic opioid therapy in chronic noncancer pain. J Pain. 2009;10(2):113–130.

Sorting out common neuropathic pain conditions

Peripheral syndromes and U.S. patients affected

Painful diabetic neuropathy; 600,000
Postherpetic neuralgia; 500,000
Cancer associated; 200,000
HIV associated; 100,000
Phantom limb pain; 50,000

Central syndromes and U.S. patients affected
 
Spinal cord injury; 120,000
CRPS I and II; 100,000
Poststroke; 30,000

Source: Irving GA. Contemporary assessment and management of neuropathic pain. Neurology. 2005;64(12 suppl 3):S21-S27.

http://journals.lww.com/nursing/Fulltext/2014/06000/Living_with_the_nightmare_of_neuropathic_pain.12.aspx

Antibodies For Neuropathic Pain

Today's post comes from painresearchfoorum.org (see link below) and discusses in some detail, one of the stories currently appearing across the 'neuropathy net' and that is the use of intravenous immunoglobulin and other antibodies to control neurological pain. The article is both long and scientific in nature and may make tricky reading but we need to know about any new developments in the search for an effective neuropathy treatment for all and is thus worth a read (or at least a 'skim')

An Autoimmune Basis for Chronic Pain?
Antibodies to potassium channel complex implicated in pain
by Megan Talkington on 4 Sep 2012

In people, autoantibodies to neuronal voltage-gated potassium channel (VGKC) complexes are associated with diverse neurologic disturbances, including seizures, encephalitis, and muscle cramps and twitching. The symptoms, many of which are attributed to antibody-induced neuronal hyperexcitability, often respond to immunotherapy. Now, researchers led by Christopher Klein at the Mayo Clinic, Rochester, Minnesota, US, have shown that the autoantibodies frequently associate with another condition: pain. In a paper published August 15 in Neurology, Klein and colleagues report pain, often chronic, in half of a group of 316 patients with VGKC-complex autoreactive antibodies. Patients with pain showed signs of hyperexcitability in sensory pathways, and, among the few who received immunotherapy, pain improved for most.

The results bolster the emerging concept that autoimmune reactions can contribute to some forms of chronic pain. In an accompanying editorial, David Bennett of King’s College London, UK, and Angela Vincent of John Radcliffe Hospital, Oxford, UK, write, “We may … be entering an exciting phase in which autoantibodies to neural antigens are recognized as having a role in the etiology of a number of hitherto poorly understood chronic pain states, opening new avenues for treatment.”

An unusual case

Klein, a neurologist, said the investigation started with one patient, a healthy 80-year-old professor who suddenly developed disabling pain in his hands and lower legs that kept him out of the classroom and home in bed. The doctors suspected neuropathy, but nerve conduction studies, and even nerve biopsy, showed no signs of damage. The physicians considered a diagnosis of psychogenic pain. But tests revealed VGKC-complex antibodies, so Klein initiated immunotherapy with an intravenous steroid. The treatment rapidly relieved the man’s pain, and the patient eventually discontinued narcotic pain relievers and returned to his normal activities.

The finding of pain with no apparent cause, coupled with the presence of VGKC antibodies and the success of immunotherapy, was unexpected, Klein said, and intriguing. VGKC autoantibodies had been linked to pain previously, but there was little information about the scope of pain symptoms in seropositive patients. To fill the gap, Klein and his colleagues embarked on a systematic review of pain symptoms in the records of 316 seropositive patients who had undergone neurologic evaluation at the Mayo Clinic. The results were surprising: 159 (50 percent) of the patients studied had pain that was not explained by other causes. In contrast, among 167 patients with one of several other neural autoantibodies, only 9 percent reported pain.

Remarkably, 45 of the patients with VGKC-complex immunoglobulin (IgG) reported pain as their only symptom. Many, like Klein’s patient, were evaluated for neuropathy or CNS disease, but no abnormalities turned up. The discovery of isolated, unexplained pain in so many “was kind of a shock to us,” Klein said.

Examination of patient records revealed that, in most cases, pain reached maximal severity within two weeks of onset, and often became chronic. The pain took a variety of forms: In half of patients, pain was isolated to extremities, while others reported total body pain, head or face pain, abdominal visceral pain, or pain in multiple locations. Patients’ descriptions suggested the pain was either neuropathic or nociceptive.

In support of an autoimmune source of pain, Klein and colleagues found that, of 16 patients in the pain group who had been treated with immunotherapy (usually for other neurologic issues), 14 showed reduced or eliminated pain symptoms. “Many of these patients were on multiple [pain] medications including narcotics, and were able to come off of them with immunotherapy,” Klein said.

Laying the blame

Were the VGKC antibodies the cause of pain? On average, titers of VGKC-complex IgG were no different in the pain group and the patients without pain. However, VGKC-complex IgG is heterogeneous: Antibodies that react with different proteins in the channel complex are thought to be associated with different clinical symptoms (Irani et al., 2010). When the Mayo group checked for antigen specificity, they detected reactivity to one accessory protein, contactin-associated protein-2 (CASPR2), more frequently in the pain group than the non-pain patients. That finding agreed with previous work by Vincent (coauthor of the accompanying editorial), who found a high incidence of pain in VGKC-complex IgG-positive patients with CASPR2 autoimmunity (Irani et al., 2010; Irani et al., 2012).

CASPR2 antibodies are not the whole answer, though. Overall, CASPR2-specific antibodies were found in just 16 percent of the seropositive patients with pain. That means that for most patients, “we still don’t know what the primary antigen is,” said Klein.

In light of the new findings, Bennett and Vincent ask in their editorial, “Should we be testing patients with chronic pain for VGKC-complex antibodies, and if so, which patients?” For patients with other telltale signs of VGKC autoimmunity, they say, the answer is yes. “The more problematic issue is those patients whose sole complaint is pain.... Larger focused studies and more detailed pain phenotyping will be required to determine the true prevalence of VGKC-complex antibodies in chronic pain cohorts.”

Klein, too, wants to know how often, and in which patients, VGKC autoantibodies might explain chronic pain. To address that question, he and his colleagues are investigating the frequency of neural autoimmunity in patients being treated at a chronic pain center.

Meanwhile, the mechanism by which the autoantibodies could cause pain remains unclear. VGKCs, also known as Kv channels, cooperate with other neuronal channels to set resting membrane potentials and regulate neuronal excitability, and some family members have already been linked to nociceptor excitability and pain (for a review, see Takeda et al., 2011). Antibodies that block VGKC function could render sensory neurons hyperexcitable, as previously seen for motor neurons. Indeed, Klein and colleagues did see evidence of abnormal sensory excitability: Excessive sweating and quantitative heat-pain hyperalgesia (C fiber allodynia) were reported only in the pain group, supporting the idea that hyperexcitability of nociceptive pathways leads to pain in patients with VGKC antibodies.

Also in support of that idea, the Mayo team recently implicated VGKC-complex autoimmunity in an unusual instance of job-related pain. They found the autoantibodies in workers at two slaughterhouses; the workers developed painful neuropathy after exposure to aerosolized brain tissue from pigs (Lachance et al., 2010; Meeusen et al., 2012). In those cases, the workers showed signs of neuronal hyperexcitability.

But Klein is cautious. “It’s an attractive theory” that the antibodies alter neuronal VGKC-complex function, “but maybe it’s more complicated than that.” In fact, the current finding “simply helps us to tell if there’s an autoimmune component,” he said. He noted that VGKCs are located on immune cells as well as neurons, so that VGKC-specific antibodies might affect neuronal excitability indirectly via cytokines, rather than targeting neurons directly. Moreover, it is possible that the VGKC-complex IgG is what Klein calls a “sentinel finding,” meaning that other—as-yet undetected—antibodies may be the real culprits.

Other labs are also providing evidence that autoantibodies play a role in pain. Recent clues point to an autoimmune basis for chronic regional pain syndrome (CRPS), where researchers have reported autoantibodies against autonomic neuron proteins in patients, including the β2 adrenergic receptor and M2 muscarinic acetylcholine receptor (Kohr et al., 2011). And, in an encouraging preliminary study, a small, randomized, placebo-controlled trial of immunotherapy with intravenous immunoglobulin reduced pain in patients with refractory CRPS (Goebel et al., 2010).

References:
Editors' Pick
Autoimmune pain: An emerging concept.
Bennett DLH, Vincent A
Neurology. 2012 Aug 15.
PMID: 22895596.
See related: An Autoimmune Basis for Chronic Pain?
Editors' Pick
Chronic pain as a manifestation of potassium channel-complex autoimmunity.
Klein CJ, Lennon VA, Aston PA, McKeon A, Pittock SJ
Neurology. 2012 Aug 15.

http://www.painresearchforum.org/news/19697-autoimmune-basis-chronic-pain

Can Chiropractic Techniques Help With Neuropathic Problems

Today's post from diabetesnewsjournal.com (see link below) addresses the perennially thorny topic of whether chiropractitioners can be of help to neuropathy sufferers. It's fair to say that 9 out of 10 neurologists will dismiss this idea with a snigger but there are many cases of nerve damage patients being helped by chiropractic techniques but it may depend on the cause of the nerve damage and whether that can be helped directly. At least this article doesn't claim that chiropractic care can 'cure' neuropathy; it makes a claim for this sort of care to be an element in an overall strategy. If you see chiropractic clinics offering 'cures' for nerve damage, please ignore them and don't waste your money or run the risk of further damage. These clinics, or so-called medical practitioners can not provide a cure - there is no cure - end of argument. However if a chiropractioner offers his or her services as part of a wider treatment strategy, it may be worth discussing it with your home doctor or neurologist. Remember though, if you're paying for this treatment, you need to be convinced that it will help.

Chiropractic Care May Help Control Peripheral Neuropathy in Diabetics
March 17th, 2015 Leonor Mateus Ferreira 

While about 60% of patients who suffer from diabetes also develop peripheral neuropathy, a nerve condition that causes tingling, numbing and tickling in the extremities, the Raveling Chiropractic Center is implementing a new technique to treat the disease. According to the center, chiropractic care may offer several benefits to treat the disorder.

Chiropractor Paul Raveling administers chiropractic care at his center with patients who suffer from peripheral neuropathy to help with the management of pain as well by treating the underlying cause. In addition to pain and numbness, the condition can include a variety of other symptoms such as prickling and throbbing or a freezing sensation. In addition, it can also damage the brain’s capacity to communicate properly with regions of the body.

“Chiropractic care is an effective treatment for peripheral neuropathy because it targets the root cause for a patient’s pain symptoms; we do not simply rely on medication to numb this pain,” explained Raveling in a press release. “While chiropractic care is not a ‘cure’ for peripheral neuropathy, it is an important part of an effective treatment program.”

“Treatment programs that cover up the symptoms are ignoring the bigger problem. As a chiropractor, I follow a ‘whole body’ approach to treatment, which means we start by addressing the underlying trigger for a patient’s pain,” he continued, explaining that a diagnostic exam is conducted in order to identify the cause of the pain and understand which specialty of care is needed in addition to chiropractic care.

The chiropractor believes that early diagnosis and treatment may reduce the severity of the motor nerve and sensory nerve damage, as well as help patients with the management of the disease. In addition, Raveling noted that the pain symptoms associated with peripheral neuropathy indicate poor health conditions and need to be evaluated carefully.

Peripheral neuropathy is a condition often associated with diabetes, despite the fact it can also be caused by autoimmune disorders, tumors, nutritional imbalances or infections, and it can even be hereditary. The nerve disorder currently affects about 20 million people in the United States, according to the National Institute of Neurological Disorders and Stroke, and while the symptoms may seem unimportant, early diagnosis may prevent further complications.

“Everyone experiences peripheral neuropathy a little differently. For some individuals, the pain may come and go, while for others, the pain may be constant. As the condition worsens, individuals may experience coordination and balance loss, along with a freezing pain, muscle weakness or extreme sensitivity to touch. I urge anyone who may be experiencing these symptoms to seek immediate treatment,” added Raveling.

The University of Kansas and Irving-based company Reata Pharmaceuticals have also recently established a partnership to develop drug technologies discovered by a professor of medicinal chemistry Brian Blagg and professor of pharmacology and toxicology Rick Dobrowsky. These compounds, called “novologues,” are expected to become a treatment option for diabetic peripheral neuropathy as well.

http://diabetesnewsjournal.com/2015/03/17/chiropractic-care-may-help-control-peripheral-neuropathy-in-diabetics/

EMA401 For Neuropathic Pain

Apologies: today's post from dddmag.com (see link below) may be a nightmare for the casual reader but it does show another progression in the search for effective treatments for neuropathic symptoms. It talks about EMA401, which is a  angiotensin II type 2 (AT2) receptor antagonist. I know; means nothing to me either even after reading the article but studies have shown that these receptor antagonists can inhibit hypersensitive responses in human neuronal tissue. This is what we are looking for - something to dampen down the hypersensitivity in our nervous system that causes such unpleasant symptoms. The pharmaceutical company that is looking very carefully at this is Spinifex Pharmaceuticals. They found that the use of EMA401 brought a significant reduction in average daily pain score versus placebo in the last week of 28 days of treatment. Results show a meaningful reduction in mean pain intensity from baseline to week four. These are of course studies and many readers will be sick to death of reading about treatments which may, or may not be effective in the future. However, having an idea of what's being done in various areas to reduce neuropathic pain, is at least reassuring. It shows that efforts are being made and mentioning what you've read to your doctors may start a chain of enquiry that may help to hasten the process.

                EMA401 for Treating Neuropathic Pain

Tom McCarthy, PhD, Chief Executive Officer, Spinifex Pharmaceuticals, Melbourne, Australia Tue, 12/04/2012

 
Neuropathic pain is a type of chronic pain and is defined by the Neuropathic Pain Special Interest Group (NeuPSIG) of the International Association for the Study of Pain as “pain arising as direct consequence of a lesion or disease affecting the somatosensory system”.1

The causes of neuropathic pain are diverse and include diabetes (diabetic neuropathy), cancer or its treatment (e.g. chemotherapy-induced neuropathy), viruses (e.g. postherpetic neuralgia), and nerve trauma (peripheral nerve injury-induced neuropathy).

NeuPSIG treatment guidelines specify first-line therapy as secondary-amine tricyclic antidepressants (nortriptyline and desipramine), dual reuptake inhibitors of serotonin and norepinephrine (duloxetine and venlafaxine), calcium channel α2-δ ligands (gabapentin and pregabalin), and topical lidocaine (5% lidocaine patch).2,3 Opioid agonists are only recommended as first-line therapy in certain clinical circumstances (e.g. neuropathic pain due to cancer).

Despite these treatment options, many neuropathic pain patients do not experience adequate pain relief and/or cannot tolerate the central nervous system (CNS) side effects that are a feature of all of these agents except for topical lidocaine. As a result, there is significant interest in the development of neuropathic pain agents that would offer a better therapeutic index and address this unmet medical need.

One approach to the treatment of neuropathic pain currently in clinical development is the use of angiotensin II type 2 (AT2) receptor antagonists. Both nonclinical and Phase 2 clinical data were recently presented at the 14th World Congress of Pain in Milan, Italy.

The AT2 receptor was originally discovered during antihypertensive drug discovery efforts in the late 1980s and early 1990s. At the time, the goal was to find molecules that blocked the binding of angiotensin II to what at that stage was thought to be a single type of receptor.4
During this medicinal chemistry process, scientists discovered that the tissue they were using for their radio-ligand assays actually contained two main types of receptor that bound angiotensin II, specifically the AT2 receptor and what became known as the angiotensin II type 1 (AT1) receptor. Ultimately, it was shown that only antagonists at the AT1 receptor reduced blood pressure, and a range of highly selective AT1 receptor antagonists have now been developed as medicines to treat hypertension (this class of medicine is referred to as ARBs).5

 Despite the success of marketed ARBs for hypertension, developers were unable to identify a human pharmaceutical use for selective AT2 receptor antagonists.6,7

In the mid-2000s, Maree Smith from the University of Queensland, Australia, established that AT2 receptor antagonists provided relief of symptoms in nonclinical models of neuropathic8 (and inflammatory9) pain. These foundational nonclinical studies, as well as more recent mechanism of action work, were presented at The 14th World Congress of Pain. Smith’s presentation was complemented by a presentation of AT2 receptor localization and pharmacology studies in human tissue from the laboratory of Praveen Anand (Imperial College London and Hammersmith Hospital), which showed that EMA401, a small-molecule oral AT2 receptor antagonist, inhibited neuronal outgrowth and inhibited hypersensitive responses in human neuronal tissue.

Having acquired Smith’s intellectual property, and building on their collaboration with Anand, Spinifex Pharmaceuticals also presented data from a Phase 2 clinical trial of EMA401 in postherpetic neuralgia patients. The design of the study is shown in Figure 1 and was a randomized, double-blind, placebo-controlled study of the safety, tolerability, and efficacy of 100-mg EMA401 administered twice daily for 28 consecutive days with a single dose on the morning of day 29 for pharmacokinetic purposes. This study met its primary endpoint: reduction in mean daily pain score versus placebo over the last week of 28 days of treatment. Results show a statistically significant and clinically meaningful reduction in mean pain intensity from baseline to week four for subjects on active treatment when compared to placebo.

 On an intent-to-treat basis, the mean pain intensity reduction from baseline after four weeks treatment was as follows: EMA401: -2.34; Placebo: -1.64; p = 0.006. A significantly greater proportion of patients on active treatment also reported a more than 30% reduction in mean pain intensity score compared to baseline (EMA401: 56.5%; Placebo: 34.1%; p = 0.003), meeting a key secondary endpoint. EMA401 was generally safe and well tolerated with no serious treatment-related adverse events reported. Full results from this study are being prepared for publication and a Phase 2 proof-of-concept study in chemotherapy-induced neuropathy is ongoing at Hammersmith Hospital, London.

References

1. Haanpää, et al. Pain.2011:152(1);14-27.

2. Dworkin, et al. Mayo Clin Proc. 2010:85(Suppl);S3-S14.

3. Dworkin, et al. Pain.2007:132; 237-251.

4. VanAtten, et al. Journal of Medicinal Chemistry.1993:36(25); 3985-3992.

5. Wexler, et al. Journal of Medicinal Chemistry.1996:39(3);625-656.

6. Steckelings, et al. Peptides.2005:. 26;1401-1409.

7. Porrello, et al. Frontiers in Bioscience.2009:14;958-972.

8. Smith and Wyse, PCT/AU2005/001975 & US 11/315,354.

9. Smith, PCT/AU2007/000339.2. Pritchard CC, Cheng HH, Tewari M. MicroRNA profiling: approaches and considerations. Nat Rev Genet. 2012 13(5):358-69.


http://www.dddmag.com/articles/2012/12/ema401-treating-neuropathic-pain

Tapentadol A Promising Option For Neuropathic Pain

Today's post from diabetesincontrol.com (see link below) talks about Tapentadol (Nucynta) being effective for diabetes-related neuropathy pain. Earlier articles on this blog (see alphabetical list to the right) have highlighted its efficacy for HIV-related neuropathy and other neuropathies also fall under its benefits (but as yet not approved for all). So why isn't this breakthrough semi-opiate ending up as a front-line treatment? The answer seems to lie in the cost and the competition between drug companies, which disregards the needs of the patients, who have been looking for an efficient chronic pain management drug with less side effects than its competitors. The FDA has approved it, which is the first major step with any new drug but doctors throughout the western world are possibly being pressured into not prescribing it due to pressure from health insurance companies who are always looking for cheaper options. It's symptomatic of a culture where economic cuts are paramount and the power of established drug company lobbies has never been stronger. However, if Tapentadol really is a better option for many patients living with neuropathy, then denying them access is at the very least, morally questionable.

Tapentadol-ER for the Treatment of Diabetes Associated Peripheral Neuropathy (DPN)  This article originally posted 26 June, 2014 and appeared in Medication, Neuropathy, Pain, Issue 735

The FDA recently approved tapentadol-ER (Nucynta ER) for the treatment of peripheral neuropathy in diabetics....

Advertisement With an increasing number of patients being diagnosed with diabetes, complications associated with the disease are becoming more common.  Diabetic peripheral neuropathy (DPN) is the most common neuropathic pain seen in patients with diabetes, affecting up to 50% of patients. It is characterized as a burning or tingling sensation that affects the lower limbs. Painful DPN is associated with increased morbidity, mortality and substantial costs to the healthcare system. Tapentadol-ER is a schedule II opioid analgesic that is commonly used for the treatment of moderate to severe chronic pain. It is unique in its dual acting mechanism in which it works as both a weak mu-opioid receptor agonist and a norepinephrine-reuptake inhibitor. This distinct mechanism is said to represent a new pharmacological class of medications: MOR-NRI. Tapentadol ER is a weak mu-opioid receptor agonist, having an 18 fold decrease in receptor affinity when compared to morphine. Despite this decrease in affinity, tapentadol ER only produces a two to three fold decrease in analgesic effects when studied in animals. It also acts on the alpha-2 receptor located on the noxious nerve fibers in the spinal cord and throughout the central nervous system, inhibiting transmission of pain impulses. The dual acting mechanism of tapentadol-ER works to control the complex pathology that is neuropathic pain. Until this approval the only options for FDA approved medications to treat diabetic peripheral neuropathy (DPN) were pregabalin and duloxetine. Tapentadol ER provides sufficient pain relief with convenient twice daily dosing. The starting dose for opioid-naïve patients is 50mg twice daily and can be titrated to an effective dose of 100mg to 250mg twice daily. The maximum daily dose is 250mg twice daily. The maximum serum concentration is increased by 17% when taken in combination with a high fat breakfast but according to package labeling may be administered without regards to food. Tapentadol-ER undergoes extensive hepatic metabolism and therefore must be adjusted in patients with hepatic impairment. The usual adjustment is extension of administration duration to once every 24 hours in patients with mild to moderate hepatic impairment (Child-Pugh Score of 7 to 9). It is contraindicated in patients with severe hepatic impairment. Tapentadol ER and its metabolites are excreted by the kidneys; however, no dose adjustments are required for patients with renal impairment. The efficacy and safety of tapentadol ER has been studied in two DPN studies. Both studies were placebo controlled randomized studies in which patients had either type 1 or type 2 diabetes and painful DPN for a period of at least six months. Pain intensity was at least a 5 on an 11 point scale. In both studies approximately two-thirds of participants were opioid-naïve. Both studies came to the conclusion that tapentadol ER provided statistically significant improvement of pain intensity as compared to that of placebo. Treatment related adverse effects were reported at 70.9% for those taking tapentadol ER and 51.8% for those taking placebo. The most common side effects were nausea, diarrhea, anxiety and dizziness. Most were mild to moderate and did not lead to discontinuation of the medication. Practice Pearls: The incidence of diabetes is on the rise as is the complication of neuropathy The FDA approval of tapentadol ER for treatment of diabetic peripheral neuropathy provides practitioners an additional therapeutic option with a convenient twice daily dosing regimen. Tapentadol ER has a unique dual mechanism suggesting that it may be particularly useful for complex pain associated with DPN. Consult Pharm. 2013 Oct;28(10):672-5. doi: 10.4140/TCP.n.2013.672 Comment from Dr. Aaron Vinik, Diabetes In Control Advisory Board member, and study author: Pain associated with DPN is a common complication of diabetes affecting 10-26% of patients for which the only approved drugs are Pregabalin and Duloxetine which at best reduce pain by 30% in about half the patients treated leaving a significant portion of the affected population without resort to significant pain relief. A paradox here is that third party payors insist that less expensive drugs such as the tricyclics should be used as first line despite the fact that they have cardiovascular cautions as well as not paying heed to the need for attention to the comorbidities of sleep loss, depression and anxiety as determinants of choice of initial therapies. However, the problem occurs when first line therapies have failed and the need for greater reduction of pain arises wherein a combination of drugs acting through different parts of the pain pathway have proved useful. The problem with this approach is that this increases the burden of drugs patients with diabetes must take with untoward effects, particularly cognitive impairment, which can have a disastrous impact on decision-making and is the cause of induced hypoglycemia and its consequences. Tapendalol represents a proposed new class of centrally acting analgesics combining two mechanisms of action: u-opiod receptor agonism and norepinephrine reuptake inhibition. Tapentadol extended release has been shown to be effective and well-tolerated for the management of severe, chronic pain in randomized, double blind, placebo-controlled and/or active comparator controlled phase 3 studies. Two studies (of which I am first author and coauthor of the second) were designed using a randomized withdrawal multicenter placebo control design and reached their primary endpoint and in August 2012 tapentadol ER received FDA approval for the mangement of pain associated with DPN in adults when a continuous around the clock opiod analgesic was needed for an extended period of time. To determine if subgroups would benefit, the data from the two studies were pooled. The results of this pooled analysis indicated that tapentadol ER is effective and well-tolerated for the management of neuropathic pain associated with DPN, improved measures of health related quality of life and had constent efficacy across different patient subgroups divided by age, gender, race, opiod experience and pain intensity. Sensitivity analyses showed that in the tepentadol arm ( n=360) compared with placebo ( n=342) the drug 54% achieved >30% pain reduction and 38.9%;50% pain reduction and the significant side effects were nausea, vomiting, dizziness, and somnolence. These figures argue in favor of using the drug as a second or third tier drug with the recognition that its effects are modest and there is the potential for habituation. Ultimately, what is needed is a drug that will reverse the pathogenic process and that the need for pain-relieving drugs will be the bandaid to be used in the interval before the damage to the nervous system has been resolved.  http://www.diabetesincontrol.com/articles/diabetes-news/16529-tapentadol-er-for-the-treatment-of-diabetes-associated-peripheral-neuropathy-dpn

What Does Neuropathic Pain Feel Like

Today's post from pain.about.com (see link below) is a short but useful description of the nature of nerve pain. There's nothing here that the experienced neuropathy patient won't know but sometimes putting your symptoms into words for others is very difficult - they just don't seem to understand - and why should they - nerve pain is pretty much unique and unless they can feel it themsleves, they won't really get what you're going through. This article will help put it into words for them - it's a, 'pass on to your friends and family' article and will help them get an idea of how you're feeling.
 

What Does Nerve Pain Feel Like?
Neuropathic Pain and its Unique Symptoms
By Erica Jacques Chronic Pain Expert Updated July 16, 2014.

Written or reviewed by a board-certified physician. See About.com's Medical Review Board.

Neuropathic pain, also called nerve pain, is one of the many classes of chronic pain. Nerve pain can be caused by nerve damage, irritation or destruction.
How Nerve Pain Feels Most people describe their chronic nerve pain with a similar set of words. Regardless of the cause, nerve pain can feel like any of the following:

Burning
Tingling
Shooting
Sharp
Stabbing
Prickling

Nerve pain may vary in intensity. For some, it can feel like mildly bothersome pins and needles. For others, the pain may be severe and nearly unbearable. Nerve pain may be localized (felt at or near the area of nerve damage) or referred (felt somewhere else in the body).

Nerve Pain Terminology

Because nerve pain is unique, it has some medical buzzwords associated with it. Nerve pain sensations may be described with these buzzwords, which include:

Allodynia: When a person experiences pain after a stimulus that shouldn’t cause pain under ordinary circumstances, it is called allodynia.
Hyperalgesia: If a person has hyperalgesia, mildly painful stimuli may be felt with greater intensity.
Dysesthesia: Dysesthesia describes some sort of impairment in sensation. It can describe pain that is felt when there is no stimulus present at all, also called spontaneous pain.

Other Symptoms Associated With Nerve Pain

Like other types of chronic pain, neuropathic conditions often cause other symptoms in addition to pain. If you have any of the following in addition to the pain described above, you may have nerve damage:

Partial or complete loss of feeling
Muscle weakness
Partial or complete paralysis
Changes in skin appearance and texture
Muscle disuse atrophy
Depression and/or anxiety
More Nerve Pain Information
Definition of Neuropathic Pain
Common Nerve Pain Conditions
What Causes Nerve Pain?

Sources:

National Pain Foundation. Neuropathic Pain: Symptoms. Accessed 2/2/10. http://www.nationalpainfoundation.org/articles/353/symptoms?PHPSESSID=9c14904e64a8ad966628202be1ce5892

The Merck Manuals Online Medical Library. Neuropathic Pain. Accessed 2/2/10. http://www.merck.com/mmpe/sec16/ch209/ch209c.html#sec16-ch209-ch209c-278

http://pain.about.com/od/typesofchronicpain/a/neuropathic_pain_symptoms.htm

Weather Related Neuropathic Pain

Many neuropathy patients seem to be affected by changes in the weather. This has long been accepted for patients with joint and rheumatic/arthritic problems but it now seems to be an issue for us too. This post relates some personal experiences found on the NeuroTalk site and suggests that if you weren't already aware of this, it might be an idea to look at your own pain patterns in relation to the weather. It would be interesting to know if this is an almost universal problem. We live and learn!

(As usual with using personal experiences from non-HIV sites, the names are not shown here, to take into account sensitivities regarding association with HIV)

Weather change and neuropathy pain

Lady from WNY
Hello,

My neuropathy is moderately severe numbness in my toes, feet, and lingers to my knees, I have had it for approx 4 to 5 years, with occasional flairs, it appears to be slow progressing, with no known cause. I am on no medication at this point for my neuropathy.

I live in WNY, I find in summer in the very hot weather, the condition stays stable.

However in August when the temperature starts to change, for example, rapidly from from 90 to 60 or 70's my feet get VERY cold, almost like they might get on a cold winter day.

I also appear to have more noticeable numbness. Once winter is here to stay for a bit, my neuropathy sort of levels out again.

Also, I find my feet very uncomfortable in air conditioning. including the car, if I have sandals on. This is a big problem, causing my feet to get so uncomfortably cold, which I am thinking must have something to do with my neuropathy.

Lately, this has been the case with the temperature, and I have been really having a time of it with significantly cold feet, also including a noticeable amount of new numbness in my feet. DARN! Just when I sort of put my neuropathy on the back burner too.

I have been wearing warmer socks at night, sneaker and socks in the day, when I realize it got cooler all of a sudden.

I try to remember to wear socks and sneakers if I am going to be in the car long with the air on, but still in the evening my feet are so uncomfortably cold, I am tempted to place my feet in warm water, or put a heating pad on them.

I also suffer from occasional migraines, so the past week with weather, in addition to many barometer changes, I have been in much discomfort. To night that includes a bad migraine, and cold numb feet.

So I hurt from top to bottom! I took aspirin, it did not help, so then a foricet for my head pain. That pill has caffiene in it, so now I am wide awake, I still don't feel good, and feel depressed on top of it all.

At any rate, does anyone else experience a difference in their neuropathy with rapid temperature changes.

Reply 1
in the western great lakes and yep, it is definitely a phenomenon. There is even a pain index map.
__________________
Some days are not so good

Others not so bad

Reply 2
My feet are always cold, even though I live in the South. I don't wear sandals ever, always those low sox with closed toe shoes, and I wear sox to bed at night, often taking them off during the night when my feet finally warm up. At the same time, if I've been on my feet too much during the day, I find my feet burning when I finally sit down--it's strange how they can be hot and cold at the same time!

Reply 3
We had such an unusually cold, for Fl, winter last year i'm going to check into getting an electric throw. Similar to the blanket, but smaller. My feet got so cold they hurt, and I don't have central heat. I did put a heating pad on my bed, not a great option for me. I am diabetic, and have a puppy who still likes to chew stuff!

Reply 4
I miss my heating pad.

I live in South Dakota and we have days where it is -25, feels like -45 with windchill. Even this summer has been horrible for my feet with the air on--this is going to be a LONG winter. My heating pad can no longer warm my feet because I can't feel the warmth and the doctor has said it could easily burn me.. plus I can't stand to have anything touching the majority of my feet. I can no longer use the heating pad on my back, though.. and that is disappointing. It's the only thing that helps the pain in my back. I was recently put on the fentanyl patch, and you can't use heating pads, hot tubs, or electric blankets (in addition to things like saunas--basically anything hot) while on the patch. The heat, even if it is far away from the patch (on your body--if the patch is on your front side and the heat on your back), it still makes the patch release more of the medicine than it is supposed to at one time and can cause an overdose. I really miss my heating pad!

Reply 5
I've had one lap robe for about 5 years, and it works when needed! Like a charm. Since it's smaller than an electric blanket..., it's easier to use when in a chair, and while attached to a cord. I almost use it as an 'area' heater? in that my spouse likes room temps a bit cooler than I need? Ergo this blanket has gotten a workout, and is still working.
Be careful and take super cautious care of Electric blankies tho... don't wash too often or too hard? and it's best to air dry them to boot. Some new throws have timers on them that turnoff after x while. For us? That's really a good safety feature. We can burn easily and not know it until too late with unpleasant consequences. SAFETY must be our ultimate factor in seeking comfort.
Can I ask? Are your hands/fingers cold? Wait until fall and seek out Target's finger tip-less gloves! I love them and have a stock of them! At times, when I'm coolish all over? I'll put on the gloves? And, I'm a happy camper again.

http://neurotalk.psychcentral.com/thread130804.html

Progress In Gene Therapy For Neuropathic Pain

Today's post from mybestlife.com (see link below) talks about the advances in gene therapy in trying to combat neuropathic pain. Scientists have identified a part of the brain (amygdala) responsibile for emotional responses to pain and to put it simply, are hoping that by injecting it with a selected virus this will block seretonin receptors responsible for pain signals. This is in response to decades of treatments using various drugs which have had limited or virtually no success. Gene therapy may well be the future in this field and the researchers have been awarded a substantial 5 year grant to investigate the possibilities. The article may seem to be a little complex but it's important to at least have some idea of the direction research is going. As always, the future is a long way off in terms of effective and inexpensive treatment but they have to start somewhere!

Gene therapy at center of UTMB effort to eliminate neuropathic pain
16th September 2013

University of Texas Medical Branch at Galveston researchers have been awarded a five-year, $1.8 million grant by the National Institute of Neurological Disorders and Stroke to apply the techniques of gene therapy to the problem of neuropathic pain — that is, pain that arises from a malfunction in the nervous system.

Neuropathic pain is a daily reality for millions of Americans, manifesting itself in a variety of life-impairing ways. Someone suffering from neuropathic pain might feel intense discomfort in response to a light touch, for example, or suddenly feel as though he or she were freezing in response to a small decrease in temperature. Caused by either accidental or disease-induced nerve damage, this kind of pain has proven very difficult to treat.

“Patients in neuropathic pain are willing to do almost anything to get relief,” said Dr. Volker Neugebauer, the co-principal investigator on the grant. “They’re in torment, often in really desperate situations.”

To make matters worse, long-term neuropathic pain often causes depression, acting through emotional mechanisms in the brain meant to underscore the importance of pain signals. Depression further increases the perception of pain, creating a vicious cycle of increasing pain and depression. And while conventional pain medicines can block the pain signal, they are usually successful for only a limited time only; eventually the pain returns when the nervous system compensates for the blockade.

Neugebauer and his UTMB colleague and co-principal investigator Thomas Green believe that a better anti-neuropathic pain strategy is to target higher brain regions and prevent the abnormal generation of persistent emotions. They focus on the amygdala, a structure best known for its role in emotional responses, including anxiety and depression and — in Neugebauer’s previous work — for its connection to pain regulation. Neugebauer and Green hypothesize that stopping abnormal activity in the amygdala by a particular type of receptor for the neurotransmitter serotonin will enable the successful treatment of neuropathic pain.

Although increased serotonin activity in the brain is generally thought of as a good thing — it’s the mechanism used by many antidepressant drugs — activation of the serotonin 2C receptor in the amygdala can cause problems, according to Neugebauer. “In neuropathic pain we see that this receptor is activated on cells that regulate output from the amygdala to brain areas where responses to potentially harmful situations are generated,” Neugebauer said. “This activity should be turned off when such response is no longer needed or useful, but these serotonin 2C receptors continue to drive amygdala output, creating a chronic pain state.”

In experiments with laboratory rats in which neuropathic pain behavior has been induced by nerve damage, Neugebauer and Green plan to investigate the possibility of “re-normalizing” the amygdala by injecting it with specially designed viruses containing genetic material that blocks cells’ generation of serotonin 2C receptors.

“The viruses that we’re using are adeno-associated viruses, very common vectors that about 80 percent of the people in our society have been exposed to,” Green said. “We’ve modified them so that they can’t replicate, and inserted a gene that instructs the amygdala cells to make small pieces of RNA that interfere with the production of serotonin 2C receptors.”

According to Green, who has been working with similar gene-therapy techniques for more than 10 years, the viral injections produce permanent effects in the brain and no off-target effects. The researchers plan to test the rats’ response to the treatment with a variety of behavioral experiments that will examine both its effect on chronic pain behavior and behaviors associated with depression.

In addition to the behavioral investigation, the project will include electrophysiological studies of amygdala activity, in an effort to further define the “circuitry” of this key pain and emotion center. It will also examine the inconsistent results achieved when chronic pain is treated with selective serotonin reuptake inhibitor antidepressants, attempting to determine whether serotonin 2C receptor activity might be responsible.

“SSRIs increase serotonin, and most of the serotonin receptors produce good effects,” Neugebauer said. “But increasing serotonin also means you’re hitting the 2C receptor as well, perhaps mediating undesirable effects. We want to take that out and then see if increasing serotonin produces consistently good effects.”

For more information
The University of Texas Medical Branch
http://www.utmb.edu/

http://www.mybestlife.com/health/News-2013-Sep/20130916-neuropathic-pain-study.htm

Autonomic Neuropathy The Neuropathic Sniper That You Dont See Coming

Today's post from dressamed.com (see link below) is a no-nonsense and easy to understand article about autonomic neuropathy. For those of you who don't already know, this is nerve damage that affects many of the 'involuntary' actions that we take for granted in our daily lives, such as breathing, digestion, sexual response, blood pressure and many more. The problem with autonomic neuropathy is that it creeps up on you over a period of time and can seriously affect the quality of your life. If you're worried you may be heading in this direction, or already know what's happening, read the article, talk to your doctor and do as much of your own research as possible. By using the search button to the right of this blog, you will find many more articles about autonomic neuropathy and how best to learn to live with it and treat its symptoms.

When Neuropathy Affects Bodily Functions 
Posted on May 11, 2016 Posted in Staff Pick by Staff Pick

Do any of these symptoms sound familiar?

Dizziness and fainting when you stand up
Difficulty digesting food and feeling really full when you’ve barely eaten anything
Abnormal perspiration – either sweating excessively or barely at all
Intolerance for exercise – no, not that you just hate it but your heart rate doesn’t adjust as it should
Slow pupil reaction so that your eyes don’t adjust quickly to changes in light
Urinary problems like difficulty starting or inability to completely empty your bladder

If they do, you could have autonomic neuropathy. Especially if you have diabetes, your immune system is compromised by chemotherapy, HIV/AIDS, Parkinson’s disease, lupus, Guillian-Barre or any other chronic medical condition.

You need to see a doctor immediately. A good place to start would be a physician well versed in diagnosing and treating nerve disease and damage, like your local clinician who specializes in our treatment protocol.

What Is Autonomic Neuropathy?

Autonomic neuropathy in itself is not a disease. It’s a type of peripheral neuropathy that affects the nerves that control involuntary body functions like heart rate, blood pressure, digestion and perspiration. The nerves are damaged and don’t function properly leading to a break down of the signals between the brain and the parts of the body affected by the autonomic nervous system like the heart, blood vessels, digestive system and sweat glands.

That can lead to your body being unable to regulate your heart rate or your blood pressure, an inability to properly digest your food, urinary problems, even being unable to sweat in order to cool your body down when you exercise.

Often, autonomic neuropathy is caused by other diseases or medical conditions so if you suffer from:

Diabetes
Alcoholism
Cancer
Systemic lupus
Parkinson’s disease
HIV/AIDS

Or any number of other chronic illnesses, you stand a much higher risk of developing autonomic neuropathy. Your best course of action is not to wait until you develop symptoms. Begin a course of preventative treatment and monitoring with a clinician to lessen your chances of developing autonomic neuropathy.

How Will The Clinician Diagnose My Autonomic Neuropathy?

If you have diabetes, cancer, HIV/AIDs or any of the other diseases or chronic conditions that can cause autonomic neuropathy, it’s much easier to diagnose autonomic neuropathy. After all, as a specialist in nerve damage and treatment, your clinician is very familiar with your symptoms and the best course of treatment.

If you have symptoms of autonomic neuropathy and don’t have any of the underlying conditions, your diagnosis will be a little tougher but not impossible.

Either way, your clinician will take a very thorough history and physical. Make sure you have a list of all your symptoms, when they began, how severe they are, what helps your symptoms or makes them worse, and any and all medications your currently take (including over the counter medications, herbal supplements or vitamins).

Be honest with your clinician about your diet, alcohol intake, frequency of exercise, history of drug use and smoking. If you don’t tell the truth, you’re not giving your clinician a clear picture of your physical condition. That’s like asking him to drive you from Montreal to Mexico City without a map or a GPS. You may eventually get to where you want to be, but it’s highly unlikely.

Once your history and physical are completed, your clinician will order some tests. Depending upon your actual symptoms and which systems seem to be affected, these tests might include: 

Ultrasound
Urinalysis and bladder function tests
Thermoregulatory and/or QSART sweat tests
Gastrointestinal tests
Breathing tests
Tilt-table tests (to test your heart rate and blood pressure regulation). Once your tests are completed and your clinician determines you have autonomic neuropathy, it’s time for treatment. 

Treatment and Prognosis

Our clinicians are well versed in treating all types of peripheral neuropathy, including autonomic neuropathy. They adhere to a very specialized treatment protocol that was developed specifically for patients suffering from neuropathy. That’s why their treatments have been so successful – neuropathy in all its forms is what they do.

Autonomic neuropathy is a chronic condition but it can be treated and you can do things to help relieve your symptoms.

Your clinician will work with you and your other physicians to treat your neuropathy and manage your underlying condition. They do this through:

Diet Planning and Nutritional Support

You need to give your body the nutrition it needs to heal.

If you have gastrointestinal issues caused by autonomic neuropathy, you need to make sure you’re getting enough fiber and fluids to help your body function properly.

If you have diabetes, you need to follow a diet specifically designed for diabetics and to control your blood sugar.

If your autonomic neuropathy affects your urinary system, you need to retrain your bladder. You can do this by following a schedule of when to drink and when to empty your bladder to slowly increase your bladder’s capacity.

Individually Designed Exercise Programs

If you experience exercise intolerance or blood pressure problems resulting from autonomic neuropathy, you have to be every careful with your exercise program. Make sure that you don’t overexert yourself, take it slowly. Your clinician can design an exercise program specifically for you that will allow you to exercise but won’t push you beyond what your body is capable of. And, even more importantly, they will continually monitor your progress and adjust your program as needed.

Lifestyle Modifications

If your autonomic neuropathy causes dizziness when you stand up, then do it slowly and in stages. Flex your feet or grip your hands several times before you attempt to stand to increase the flow of blood to your hands and feet. Try just sitting on the side of your bed in the morning for a few minutes before you try to stand.

Change the amount and frequency of your meals if you have digestive problems.

Don’t try to do everything all at once. Decide what really needs to be done each day and do what you can. Autonomic neuropathy is a chronic disorder and living with any chronic condition requires adaptations. Your clinician knows this all too well and will work with you to manage your level of stress and change your daily routines to help you manage your condition and your life.

All of these changes in conjunction with medications, where needed, will make it easier to live with autonomic neuropathy and lessen the chances of serious complications. Early intervention with a NeuropathyDR® clinician is still the best policy if you have any of the underlying conditions that can cause autonomic neuropathy. But if you already have symptoms, start treatment immediately.

About The Author

Dr. John Hayes, Jr. is an Evvy Award Nominee and author of “Living and Practicing by Design” and “Beating Neuropathy-Taking Misery to Miracles in Just 5 Weeks!”. His work on peripheral neuropathy has expanded the specialty of effective neuropathy treatments to physicians, physical therapists and nurses. A free Ebook, CD and information packet on his unique services and trainings can be obtained by registering your information at neuropathydr.com. 

Syndicated by EzineArticles

https://www.dressamed.com/root/when-neuropathy-affects-bodily-functions/

Back To The Zebra Fish A Neuropathic Wonder! Vid

Today's video from directorsblog.nih.gov (see link below) is so short (and silent) you might be forgiven for wondering why I bothered but it shows the remarkable ability of the zebra fish to regenerate its nerves when damaged. We're back to the ubiquitous zebra fish again - it pops up all over the neurology internet and has done for some time, as scientists try to discover why it does this and whether the science can somehow be applied to humans with damaged nerves. It's not for the want of trying as the article below shows. Let's hope they can eventually apply zebra fish self-healing to people living with neuropathy - now wouldn't that be something!!

Cool Videos: Regenerating Nerve Fibers
Posted on October 13, 2016 by Dr. Francis Collins




If you enjoy action movies, you can probably think of a superhero—maybe Wolverine?—who can lose a limb in battle, yet grow it right back and keep on going. But could regenerating a lost limb ever happen in real life? Some scientists are working hard to understand how other organisms do this. As shown in this video of a regenerating fish fin, biology can sometimes be stranger than fiction. The zebrafish (Danio rerio), which is a species of tropical freshwater fish that’s an increasingly popular model organism for biological research, is among the few vertebrates that can regrow body parts after they’ve been badly damaged or even lost. Using time-lapse photography over a period of about 12 hours, NIH grantee Sandra Rieger, now at MDI Biological Laboratory, Bar Harbor, ME, used a fluorescent marker (green) to track a nerve fiber spreading through the skin of a zebra fish tail fin (gray). The nerve regeneration was occurring in tissue being spontaneously formed to replace a section of a young zebra fish’s tail fin that had been lopped off 3 days earlier.

 Along with other tools, Rieger is using such imaging to explore how the processes of nerve regeneration and wound healing are coordinated. The researcher started out by using a laser to sever nerves in a zebrafish’s original tail fin, assuming that the nerves would regenerate—but they did not! So, she went back to the drawing board and discovered that if she also used the laser to damage some skin cells in the tail fin, the nerves regenerated. 

Rieger suspects the answer to the differing outcomes lies in the fact that the fish’s damaged skin cells release hydrogen peroxide, which may serve as a critical prompt for the regenerative process [1]. Rieger and colleagues went on discover that the opposite is also true: when they used a cancer chemotherapy drug to damage skin cells in a zebra fish tail fin, it contributed to the degeneration of the fin’s nerve fibers [2]. Based on these findings, Rieger wants to see whether similar processes may be going on in the hands and feet of cancer patients who struggle with painful nerve damage, called peripheral neuropathy, caused by certain chemotherapy drugs, including taxanes and platinum compounds. For some people, the pain and tingling can be so severe that doctors must postpone or even halt cancer treatment. 

Rieger is currently working with a collaborator to see if two protective molecules found in the zebra fish might be used to reduce or prevent chemotherapy-induced peripheral neuropathy in humans. In recent years, a great deal of regenerative medicine has focused on learning to use stem cell technologies to make different kinds of replacement tissue. Still, as Rieger’s work demonstrates, there remains much to be gained from studying model organisms, such as the zebra fish and axolotl salamander, that possess the natural ability to regenerate limbs, tissues, and even internal organs. Now, that’s a super power we’d all like to have. 

Reference: [1] Hydrogen peroxide promotes injury-induced peripheral sensory axon regeneration in the zebrafish skin. Rieger S, Sagasti A. PLoS Biol. 2011 May;9(5):e1000621 [2] Paclitaxel-induced epithelial damage and ectopic MMP-13 expression promotes neurotoxicity in zebra fish. Lisse TS, Middleton LJ, Pellegrini AD, Martin PB, Spaulding EL, Lopes O, Brochu EA, Carter EV, Waldron A, Rieger S. Proc Natl Acad Sci U S A. 2016 Apr 12;113(15):E2189-E2198. Links: Chemotherapy-Induced Peripheral Neuropathy (National Cancer Institute/NIH) Learning About Human Biology From a Fish (National Institute of General Medical Sciences/NIH) Sandra Rieger (MDI Biological Laboratory, Bar Harbor, ME) NIH Support: National Institute of Dental and Craniofacial Research; National Institute of General Medical Sciences; National Institute of Neurological Disorders and Stroke

https://directorsblog.nih.gov/2016/10/13/cool-videos-regenerating-nerve-fibers/

Neuropathic Pain And Sadness Vid

Today's video is one of a larger series made by Andy Bailey, who is a multiple sclerosis patient with a great attitude to his disease and life in general. You may not agree with some of his conclusions regarding his neuropathic pain but much of what he says is definitely close to what many of us think. There is something uplifting about this video and the guy's sense of humour and you won't be wasting five and a half minutes of your life watching it. Maybe more people could consider putting their experiences of living with neuropathy onto video - there's no doubt that seeing how other people deal with it helps us put our own problems in perspective a bit more.


Neuropathic pain and sadness... multiplesclerosis
Andy Bailey: Published on 22 Jan 2013

Do you get neurological pain? What is that about? also, brain fog and how I combat MS induced depression/sadness



 

http://www.angeranddepression.com/22-jan-2013-neuropathic-pain-and-sadness-multiplesclerosis/

Venoms For Neuropathic Pain

Today's post is from sciencedaily.com (see link below) and talks about the pain killing properties of certain venoms. This seems to be a recurring theme - the same has been said of Black Widow Spider and certain snake venoms but hey, if it works!

Pinch Away the Pain: Scorpion Venom Could Be an Alternative to Morphine
ScienceDaily (Feb. 21, 2010)

Scorpion venom is notoriously poisonous -- but it might be used as an alternative to dangerous and addictive painkillers like morphine, a Tel Aviv University researcher claims.

Prof. Michael Gurevitz of Tel Aviv University's Department of Plant Sciences is investigating new ways for developing a novel painkiller based on natural compounds found in the venom of scorpions. These compounds have gone through millions of years of evolution and some show high efficacy and specificity for certain components of the body with no side effects, he says.

Peptide toxins found in scorpion venom interact with sodium channels in nervous and muscular systems -- and some of these sodium channels communicate pain, says Prof. Gurevitz. "The mammalian body has nine different sodium channels of which only a certain subtype delivers pain to our brain. We are trying to understand how toxins in the venom interact with sodium channels at the molecular level and particularly how some of the toxins differentiate among channel subtypes.

"If we figure this out, we may be able to slightly modify such toxins, making them more potent and specific for certain pain mediating sodium channels," Prof. Gurevitz continues. With this information, engineering of chemical derivatives that mimic the scorpion toxins would provide novel pain killers of high specificity that have no side effects.

An ancient Chinese secret?

In his research, Prof. Gurevitz is concentrating on the Israeli yellow scorpion, one of the most potent scorpions in the world. Its venom contains more than 300 peptides of which only a minor fraction has been explored. The reason for working with this venom, he says, is the large arsenal of active components such as the toxins that have diversified during hundreds of millions of years under selective pressure. During that process, some toxins have evolved with the capability to directly affect mammalian sodium channel subtypes whereas others recognize and affect sodium channels of invertebrates such as insects. This deviation in specificity is for us a lesson of how toxins may be manipulated at will by genetic engineering, he says.

While the use of scorpion venom to treat some body disorders seems counter-intuitive, the Chinese have recognized its effectiveness hundreds of years ago. "The Chinese, major practitioners of what we call 'alternative medicine,' use scorpion venom, believing it to have powerful analgesic properties," Prof. Gurevitz says. Some studies have also shown that scorpion venom can be used to treat epilepsy. "We study how these toxins pursue their effects in the Western sense to see how it could be applied as a potent painkiller."

Using an approach called "rational design" or "biomimicry," Prof. Gurevitz is trying to develop painkillers that mimic the venom's bioactive components. The idea is to use nature as the model, and to modify elements of the venom so that a future painkiller designed according to these toxins could be as effective as possible, while eliminating or reducing side effects.

No more morphine addicts

Finding a new and effective pain medication could solve one of the biggest problems in the medical world today. Pain is an important physiological response to danger, physical injury and poor health, yet doctors need to reduce extreme pain in patients which aspirin could never palliate. To date, opiate-derived painkillers have been quite effective, but the medical community is eager to find other solutions due to the risks associated with their use.

"This new class of drugs could be useful against serious burns and cuts, as well as in the military and in the aftermath of earthquakes and natural disasters. Instead of running the risk of addiction, this venom-derived drug, mimicking the small peptide toxin, would do what it needs to do and then pass from the body with no traces or side-effects," Prof. Gurevitz says.

http://www.sciencedaily.com/releases/2010/02/100216163341.htm

Can Music Soothe Neuropathic Pain

Today's post from discovermagazine.com (see link below) takes a look at music as a complementary therapy for people living with pain. Marion Good, a professor of nursing at Case Western Reserve University, first noticed the therapeutic powers of music while working as a nurse on a neurology unit and is now convinced that it can be used in conjunction with prescribed pain killers. It's an interesting idea that's free and easy to try out for yourself. In a way, it's a relaxation technique and we all know that the more relaxed we are, the less intense the pain. Heavy metal might not be the wisest choice unless you normally drift off to sleep to the dulcet tones of Black Sabbath!

Music for Pain
by Victor Limjoco

Marion Good loves to play music in her spare time. But as a professor of nursing at Case Western Reserve University's Frances Payne Bolton School of Nursing, she also prescribes it for pain relief. Now, a new study finds that while music won't replace painkillers, it can boost their effectiveness.

Good's interest in researching music for pain began when, as a nurse on a neurology unit, she worked with patients suffering from back pain. "I would bring music into the room—soft, quiet music. Their faces just relaxed ... pretty soon they fell asleep," she says. "I had to tiptoe out of the room and come back an hour or two later to pick up my tape recorder."

Good has been testing music with post-operative patients for more than 15 years. "I found that music does reduce pain up to about 31 percent in my studies, in addition to medication," she says.

The conclusion of a systematic analysis combining 51 clinical studies is music to her ears. The Cochrane Review of Evidence-Based Healthcare found that patients exposed to music rate their pain as less intense and even use lower doses of painkillers.

On a zero-to-10 scale, patients reported an average drop of .5 in their pain rating when listening to music. "It's not a huge amount," Good says, "but that's an average and for some people, it will be more, and for some it will be less." Since music has no side effects, she points out, there's no risk in trying it.

Good's latest study, conducted with Sandra Siedlecki of the Cleveland Clinic Foundation and published in the Journal of Advanced Nursing, found that patients with chronic pain who added music for pain relief got other benefits too.

"We found that music reduced pain, reduced anxiety, reduced depressive symptoms, and reduced pain disability," she says.

While the Cochrane Review cautions that music should not replace traditional primary treatments for pain, Good hopes this evidence will persuade other healthcare providers to consider music therapy as a complement to traditional treatment.

http://discovermagazine.com/2006/aug/musicnopain/?searchterm=neurology