Anti Epileptics For Neuropathy An Australian View

Today's post from nps.org.au (see link below) is a very interesting look at the workings of anti-epileptic drugs in the treatment of neuropathy. It's always interesting to look at how different countries approach the treatment of chronic pain and/or neuropathy. In Australia, it's generally recommended that neuropathy patients are treated with a progressive scale of treatments, beginning with non-drug options and moving on, if necessary, via anti-depressants and anti-epilepsy drugs to opiates. This ties into a general world-wide approach to the disease but the article agrees that neuropathy is hard to treat, whatever you use to control the symptoms. Regarding anti-epileptic drugs, it concludes that the only two that are effective (however limited) are gabapentin and pregabalin. However, once again, this ignores Pfizer's own advice that pregabalin (Lyrica) is not suitable for particular groups of neuropathy sufferers (HIV- and diabetic neuropathy patients for instance) and it does seem strange that that advice from the makers is being overlooked across the world. This may partly be due to that fact that doctors see some successes with neuropathy patients being treated with Pregabalin but that doesn't take into account whether the drug is actually good for you or not. Whatever the issues around pregabalin, this is an interesting article for those already on anti-epileptics, or about to begin using them.

Treating neuropathic pain with anticonvulsants — which ones work?
Published in Health News and Evidence Date published: 10 January 2014

Summary
 
Neuropathic pain is a common form of chronic pain, with an array of drugs available for its treatment, including anticonvulsants.

A recent Cochrane review assessed the evidence around efficacy and safety for 10 anticonvulsant drugs used to treat neuropathic pain and found evidence of efficacy for only 2 — gabapentin and pregabalin.
The study provides support for the use of pregabalin and gabapentin in treatment of neuropathic pain, but was not able to distinguish between the 2 drugs in terms of efficacy for the treatment of painful diabetic neuropathy or postherpetic neuralgia. Nor was the study able to identify patients most likely to benefit from treatment with either drug.
Gabapentin and pregabalin are TGA-approved in Australia for the treatment of neuropathic pain. Currently, pregabalin is PBS subsidised when prescribed for neuropathic pain, and gabapentin is subsidised for this indication only under the RPBS. 

Practice points
Use a comprehensive clinical assessment to determine the cause of pain, its nature and severity, and the effect of the pain on the patient.1
Provide each patient with an individual management plan based on this assessment.1
Use a multidisciplinary approach to management that includes patients in decision making, and consider non-drug treatments first.1,2
Consider the TCA amitriptyline as first line if drug treatment is required.3
Consider next an anticonvulsant such as pregabalin or gabapentin if first line is unsuccessful.3
Conduct early and regular clinical reviews of patients on drug treatment.4
Refer patients whose pain relief is inadequate to a pain specialist, a multidisciplinary pain clinic or a palliative care service.3,5
Chronic pain in Australia

Chronic pain affects 1 in 5 Australian adults,6,7 with incidence increasing with age. Much of the burden of patient management falls on general practitioners.1

Chronic pain is Australia's third most costly health condition after cardiovascular diseases and musculoskeletal conditions.8 The total cost of chronic pain to the Australian economy was reported to be $34 billion in 2007, including $7 billion in health system costs.8

Neuropathic pain

Neuropathic pain is a form of chronic pain, and is difficult to treat effectively.3

Neuropathic pain is defined as pain caused by a lesion or disease of the somatosensory system9 and is usually described as burning, painful, cold or electric shocks. These symptoms may occur alongside tingling, pins and needles, numbness or itching.3,10

Causes include nerve damage, which can be followed by changes to the central nervous system.11 This condition can present for months or years, causing significant, disabling, moderate to severe pain.11
Neuropathic pain: Australian guidelines

Australian guidelines recommend that patients with chronic pain, such as neuropathic pain, have an individualised management plan. This plan should be linked to a comprehensive patient assessment to determine the cause of pain, its nature and severity as well as the effect of the pain on the patient.1

There is no generally accepted 'stepwise' approach to treatment of neuropathic pain. Australian guidelines recommend non-drug approaches first.1,5 Many drugs are available for the treatment of neuropathic pain, with TCAs and anticonvulsants the drugs of choice.3,5 However, comparative studies are limited, there is no evidence for differences in the relative efficacies of individual drugs5,11 and these treatments are often associated with adverse events.

Guidelines recommend starting drug therapy for neuropathic pain with a TCA (such as amitriptyline) or an anticonvulsant.3,5 The anticonvulsants gabapentin and pregabalin are recommended by Therapeutic Guidelines as a second-line treatment of neuropathic pain after the TCA amitriptyline.3 The dose of the drugs can be escalated at weekly intervals if tolerated, but it may take several weeks to achieve clinical efficacy.

*TCAs are an established treatment for neuropathic pain but are not approved by the TGA for this indication.
Efficacy and safety of anticonvulsant drugs for neuropathic pain: Cochrane review

The Cochrane Collaboration recently reviewed the efficacy and safety of 10 anticonvulsant drugs for the treatment of neuropathic pain and fibromyalgia.11 This was not a new systematic review of individual studies,11 but compiled data from the 10 previous Cochrane reviews published between 2009 and 201312-21 and comprising 17,955 participants (with at least moderate pain) from 91 studies.11-21

These studies were placebo controlled, double blind, randomised controlled trials. Results were presented for each different drug for 3 different neuropathic pain conditions — painful diabetic neuropathy, postherpetic neuralgia and central neuropathic pain — and for fibromyalgia. This article will focus on the findings related to neuropathic pain.

Evidence of pain reduction for gabapentin and pregabalin only

This Cochrane review reported on efficacy as well as patient impression of improvement, and investigated outcomes including patient-reported pain relief of 50% or more and Patient Global Impression of Change (PGIC).11 Results were reported in terms of whether patients were more likely to achieve the benefit with the treatment than by taking placebo.11

A reduction in pain intensity of 50% or more is considered to be a clinically relevant benefit.3

The Patient Global Impression of Change (PGIC) is a measure of global improvement with treatment where participants rate their improvement from 'very much improved' to 'very much worse' with 'no change' as the mid-point.22

Among the 10 anticonvulsants studied, evidence of pain reduction was only found for gabapentin and pregabalin.11 People taking either of these drugs were more likely to report pain relief of 50% or more for painful diabetic neuropathy and postherpetic neuralgia than those taking placebo†.11 People taking pregabalin for the treatment of central neuropathic pain were also more likely (compared to placebo) to report pain relief of 50% or more†.11

The number of patients who would need to be treated with pregabalin or gabapentin for one patient to see this improvement was estimated to range from 4 to 10 for >=50% reduction in pain.11 Therapeutic Guidelines advises that for pain treatment to be considered to be effective, the number needed to treat for one person to achieve an outcome should be between 2 and 5.3
Further findings

The Cochrane review also found that people taking gabapentin for painful diabetic neuropathy or postherpetic neuralgia were more likely to rate their improvement as 'excellent' or 'very good or excellent' than those people taking placebo*.11

People taking lacosamide or pregabalin for painful diabetic neuropathy were more likely to rate their improvement as 'very good or excellent' than those people taking placebo*.11 The data suggest that the benefit with pregabalin may be dose dependent, as a benefit was seen with the 600mg/day dose but not the 300mg/day dose. Data for other drugs was not presented.11
*These results were statistically significant. The rating of improvement by patients was determined using the PGIC.

Carbamazepine: an accepted treatment for neuropathic pain but insufficient evidence of effect

Carbamazepine is an accepted treatment in Australia for neuropathic pain but is not TGA-approved for this indication.5

This Cochrane review found that evidence of efficacy for carbamazepine was of low quality and consequently likely to be subject to a number of biases that would overestimate efficacy.11 Most studies with carbamazepine were less than 4 weeks' duration, in contrast to studies with other drugs that were of 10-12 weeks or longer.11
Safety

The risk of adverse events in people taking anticonvulsant drugs is high, with CNS adverse events relatively common and often dose dependent, particularly for pregabalin and lacosamide.11 In this Cochrane review, available data showed that only oxcarbazepine statistically significantly increased the risk of a serious adverse event in people taking anticonvulsants for either neuropathic pain or fibromyalgia compared to those taking placebo.11

Limitations of the study

This Cochrane review benefits from, and is also limited by, the fact that the data are taken solely from previous Cochrane reviews. While this ensures that each study included is of a comparative and high standard, it also means that some trials would have been omitted.11 For example, levetiracetam does not feature in a Cochrane review and therefore was not assessed in this study, although it has been tested in other randomised controlled trials.11
Conclusions: pregabalin and gabapentin are the preferred anticonvulsants

While all evidence considered in this Cochrane review was described as 'second tier' or lower due to the potential for biases to overestimate efficacy, the results provide support for current Australian guidelines.3
Treatment best practice and implications for patients
Assess the nature of the pain experience and inform people of realistic outcomes with treatment.23,24
Provide each patient with an individualised management plan based on a comprehensive clinical assessment of their pain.1
The primary treatment goal in most cases is to make the pain tolerable — not usually to eliminate the pain.23
Aim for medium-term drug therapy with a drug holiday after 6 months. Patients who relapse during a drug holiday can resume treatment.
Conduct early and regular clinical reviews.

This Cochrane review supports the use of pregabalin and gabapentin as part of a management plan for neuropathic pain, but is not able to distinguish between their efficacies for treatment of painful diabetic neuropathy or postherpetic neuralgia. Drug therapy is best used as part of a multifaceted, multidisciplinary, active self-management approach to the physical, psychological, social and vocational impacts of neuropathic pain.2

Analgesic failure is common in the treatment of neuropathic pain and there is currently no evidence to inform which patients are most likely to benefit from what drugs and indeed the order in which drugs should be taken to optimise outcomes.11 However, patients who do not respond to one drug may respond to another, even within the same drug class.5 Combination drug therapy may be needed by many patients.24,25 A specific combination of treatments cannot be recommended due to the limited number of studies for any combination therapy, as well as other study factors, such as the limited trial size and duration.25

More information is available from NSW Health.

Refractory, severe neuropathic pain

Assistance from a pain specialist and a multidisciplinary pain service may be required for refractory, severe neuropathic pain, as treatment options are complex.2
Further information
Pregabalin (Lyrica) for neuropathic pain (NPS Medicinewise RADAR: April 2013).26
Information for patients

Patient information leaflet: Key points for patients about chronic pain (Therapeutic Guidelines).

References

1. eTG complete [Internet]. Therapeutic Guidelines: Analgesic. Melbourne: 2012. [Online] (accessed 19 December 2013).
2. Australian Pain Society. Evidence-based recommendations for the pharmacological management of neuropathic pain. Position Statement, June 2008. [Online] (accessed 20 October 2012)
3. eTG complete [Internet]. Therapeutic Guidelines: Neurology. Melbourne: 2011. [Online] (accessed 19 December 2013).
4. National Institute for Clinical Excellence (Nice). Neuropathic Pain: The pharmacological management of neuropathic pain in adults in non-specialist settings. NICE Clinical Guideline 173. Manchester: National Institute for Clinical Excellence, 2013. [Full text]
5. Rossi S e. Australian Medicines Handbook, 2013. Adelaide.
6. Hogg MN, Gibson S, Helou A, et al. Waiting in pain: a systematic investigation into the provision of persistent pain services in Australia. Med J Aust 2012;196:386-90. [PubMed]
7. Blyth FM, March LM, Brnabic AJ, et al. Chronic pain in Australia: a prevalence study. Pain 2001;89:127-34. [PubMed]
8. Access Economics Pty  Ltd. The high price of pain: the economic  impact of persistent pain in Australia. Sydney Deloite Access Economics, 2007 [Full text]
9. Jensen TS, Baron R, Haanpaa M, et al. A new definition of neuropathic pain. Pain 2011;152:2204-5. [PubMed]
10. Votrubec M, Thong I. Neuropathic pain — a management update. Aust Fam Physician 2013;42:92-7. [PubMed]
11. Wiffen PJ, Derry S, Moore RA, et al. Antiepileptic drugs for neuropathic pain and fibromyalgia — an overview of Cochrane reviews. Cochrane Database Syst Rev 2013;11:CD010567. [PubMed]
12. Birse F, Derry S, Moore RA. Phenytoin for neuropathic pain and fibromyalgia in adults. Cochrane Database Syst Rev 2012;5:CD009485. [PubMed]
13. Corrigan R, Derry S, Wiffen PJ, et al. Clonazepam for neuropathic pain and fibromyalgia in adults. Cochrane Database Syst Rev 2012;5:CD009486. [PubMed]
14. Gill D, Derry S, Wiffen PJ, et al. Valproic acid and sodium valproate for neuropathic pain and fibromyalgia in adults. Cochrane Database Syst Rev 2011:CD009183. [PubMed]
15. Hearn L, Derry S, Moore RA. Lacosamide for neuropathic pain and fibromyalgia in adults. Cochrane Database Syst Rev 2012;2:CD009318. [PubMed]
16. Moore RA, Straube S, Wiffen PJ, et al. Pregabalin for acute and chronic pain in adults. Cochrane Database Syst Rev 2009:CD007076. [PubMed]
17. Moore RA, Wiffen PJ, Derry S, et al. Gabapentin for chronic neuropathic pain and fibromyalgia in adults. Cochrane Database Syst Rev 2011:CD007938. [PubMed]
18. Wiffen PJ, Derry S, Lunn MP, et al. Topiramate for neuropathic pain and fibromyalgia in adults. Cochrane Database Syst Rev 2013;8:CD008314. [PubMed]
19. Wiffen PJ, Derry S, Moore RA. Lamotrigine for acute and chronic pain. Cochrane Database Syst Rev 2011:CD006044. [PubMed]
20. Wiffen PJ, Derry S, Moore RA, et al. Carbamazepine for acute and chronic pain in adults. Cochrane Database Syst Rev 2011:CD005451. [PubMed]
21. Zhou M, Chen N, He L, et al. Oxcarbazepine for neuropathic pain. Cochrane Database Syst Rev 2013;3:CD007963. [PubMed]
22. Dworkin RH, Turk DC, Farrar JT, et al. Core outcome measures for chronic pain clinical trials: IMMPACT recommendations. Pain 2005;113:9-19. [PubMed]
23. Moulin DE, Clark AJ, Gilron I, et al. Pharmacological management of chronic neuropathic pain - consensus statement and guidelines from the Canadian Pain Society. Pain Res Manag 2007;12:13-21. [PubMed]
24. Dworkin RH, O'Connor AB, Audette J, et al. Recommendations for the pharmacological management of neuropathic pain: an overview and literature update. Mayo Clin Proc 2010;85:S3-14. [PubMed]
25. Chaparro LE, Wiffen PJ, Moore RA, et al. Combination pharmacotherapy for the treatment of neuropathic pain in adults. Cochrane Database Syst Rev 2012;7:CD008943. [PubMed]
26. National Prescribing Service. Pregabalin (Lyrica) for neuropathic pain. RADAR; April 2013. [Full text]

http://www.nps.org.au/health-professionals/health-news-evidence/latest-issue/treating-neuropathic-pain

Anti Opioid Measures Affect Genuine Pain Sufferers

Today's post from the always excellent pain-topics.org (see link below) talks about the current political hysteria concerning opioids and opioid abuse across the world. True there are recreational users who abuse both the drugs and the system but there are also so many neuropathy and other non-cancer pain sufferers who depend on these drugs to get by each day. Authorities in many lands are introducing stringent measures to control opioid abuse but innocent people are being caught up in the backlash and being denied the drugs they need and deserve. You can almost understand the motives behind this when talking about drug abuse but if the reason also involves money, as is suggested here in Australia, then it is clearly unacceptable to chronic pain sufferers. A very interesting article.

Opiophobia Alive & Well in Oz
Posted by SB. Leavitt, MA, PhD Thursday, January 24, 2013

With all the recent ruckus over prescription opioids and sensational news headlines in the American press inciting fears of these medications, it is easy to believe that the United States is the only country facing such challenges. Apparently, the news is even worse from “down under” in Australia.

According to a brief news item — by Renee Viellaris and appearing in The Australian on January 19, 2013 [here] — physicians will “begin weaning some patients off pain medication as the nation's insatiable habit of pill popping has left health and law enforcement agencies buckling under pressure.” New pharmaceutical guidelines, to be presented this year to state and federal health ministers, will disallow prescribing some patients with “highly addictive and popular pain pills.”

The news report claims that the move has been prompted by the financial drain on the federally-funded Pharmaceutical Benefits Scheme (PBS) from excessive analgesic prescribing, misuse of the medicines, and “research showing long-term use of opioids is counterproductive.” Based on 2010 figures from the Australian National Centre for Education and Training on Addiction (NCETA), in that single year demand for subsidized prescriptions for two types of popular analgesics — oxycodone and fentanyl — cost taxpayers an extra $18 million [$18.9 million USD].

Dr. Steve Hambleton, federal president of the Australian Medical Association, confirmed that “some patients with noncancer pain would have to be weaned off the drugs because they were too expensive and were no longer clinically appropriate. Patients with long-term back or hip pain and those with sporting injuries who take the popular drugs face being directed to alternative therapies, including yoga.”

Hambleton called for more money from government to set up chronic pain clinics in hospitals, but conceded that the new regulations will dramatically change how pain is treated, and at a time when policy makers are also coping with an ageing population. “Some patients will have to be weaned off (and will have to do) things like physical therapy and focus on what you can do and not what you can't — more of a positive attitude,” he said in the news article.

The news report concludes that, “Research provided by NCETA shows that the per capita amount of morphine-equivalent drugs Australians are taking has exploded in the past 30 years.” Furthermore, “the number of Queenslanders on opioid dependence programs is dramatically increasing.”

COMMENTARY: The news report, brief as it is, tells a grim story of what may lie ahead for patients with chronic pain in Oz. And, unfortunately, this is not unlike what is occurring or may happen in other parts of the world, including the U.S.

Our quick scan of the websites of Australian organizations — Chronic Pain Australia serving patients/advocates, and the Australian Pain Society serving healthcare professionals — found no mention of these dire developments. Among other concerns, it would be interesting to know of what research evidence authorities are examining that proves the long-term use of opioid analgesics is “counterproductive.”

The news article notes that the number of persons in Queensland entering opioid-dependence treatment programs has been “dramatically increasing.” However, an accompanying chart shows the rise was only 19% — from roughly 4,900 to 5,800 persons — during the 5-year span 2008 to 2012. It does not say what proportion was attributable to prescription opioid abuse/addiction, or whether this was actually a favorable trend suggesting that more persons with substance-use problems are seeking and getting much needed care. [The U.S. CDC had presented some time ago similarly puzzling data on treatment-program admissions, discussed in an UPDATE here.]

Saving money on federally-funded prescription plans may seem like a worthwhile goal, but we wonder if authorities have considered the unintended consequences — financial and otherwise — of leaving large populations adrift to suffer chronic pain. It seems rather cavalier to suggest that these patients should adopt more positive attitudes and participate in alternative therapies, like yoga, since such interventions only work if they can get out of bed and move nimbly about without adequate pain-relieving medication.

http://updates.pain-topics.org/2013/01/opiophobia-alive-well-in-oz.html

Important Information About Anti Seizure Drugs And HIV Meds

Today's post from dailyrx.com (see link below) looks at something which maybe alarming for HIV patients with neuropathy, who are currently prescribed anti-seizure or anti-convulsion drugs (for instance, Gabapentine, Lamotrigine and others). The American Academy of Neurology issued guidelines in January, 2012, that urge caution for doctors prescribing seizure drugs for patients on anti-retrovirals because the they can directly affect the working of the HIV meds. It is important that you consult your doctor/HIV specialist if you fall into this category (as many people with neuropathy and HIV do). Your doctor may not be aware of these latest developments and may need to adjust the dosage of your meds, or even change them.

HIV Patients Choose Seizure Drugs Carefully
By:Lindsay Patterson Reviewed by: Joseph V. Madia, MD  January 8, 2012

Seizure drugs for HIV AIDS patients have new AAN guidelines

(dailyRx News) A new guideline from the American Academy of Neurology urges caution for doctors prescribing seizure drugs for patients also taking anti-retroviral drugs for HIV.

Seizures are common among people infected with HIV, and 55 percent of people taking anti-retroviral drugs (ARVs) are also taking anti-epileptic drugs (AEDs) to prevent seizures.

But certain types of these drugs, when taken together, can have dangerous interactions or cause anti-HIV medications to fail.


"Ask your doctor if your medications follow the new guideline."

The AAN guideline is the first formal guideline for treating patients who are taking bothARVs and seizure drugs.

The paper supporting the new guideline reports that worldwide use of both ARVs and seizure drugs is substantial. HIV patients may experience seizures resulting from other conditions that took advantage of their weakened immune system.

Seizure drugs are also used to treat other conditions, such as bipolar disorder and neuropathic pain.

According to the guideline, there are several negative outcomes that can come from different drug combinations. Some interactions can cause either drug to become more toxic to the body.

Seizure drugs that work to reduce ARV levels in the blood, like phenytoin, phenobarbital and carbamazepine, can make the patient's anti-HIV treatment less effective, leading to the disease progressing towards AIDS, and resistance to ARVs.

These dangerous interactions are of special concern for patients in developing countries. In Sub-Saharan Africa, for example, HIV is widespread and choice of drugs is limited.

Lead guideline author Dr. Gretchen L. Birbeck of Michigan State University advised that patients know exactly what drugs they're taking, and give that information to all of their healthcare providers to avoid dangerous interactions in drugs prescribed by different doctors.

The guideline also recommended dosages for each drug. The full text of the guideline follows:

“Patients receiving phenytoin may require a lopinavir/ritonavir dosage increase of 50% to maintain unchanged serum concentrations (Level C). Patients receiving valproic acid may require a zidovudine dosage reduction to maintain unchanged serum zidovudineconcentra- tions (Level C). Coadministration of valproic acid and efavirenz may not require efavirenz dosage adjustment (Level C).

Patients receiving ritonavir/atazanavir may require a lamotrigine dosage increase of 50% to maintain unchanged lamotrigine serum concentrations (Level C). Coadmin- istration ofraltegravir/atazanavir and lamotrigine may not require lamotrigine dosage adjustment (Level C). Coadministration of raltegravir and midazolam may not require midazolamdosage ad- justment (Level C).

Patients may be counseled that it is unclear whether dosage adjustment is necessary when other AEDs and ARVs are combined (Level U). It may be important to avoid enzyme-inducing AEDs in people on ARV regimens that include protease inhibitors ornonnucleo- side reverse transcriptase inhibitors, as pharmacokinetic interactions may result in virologic fail- ure, which has clinical implications for disease progression and development of ARV resistance.

If such regimens are required for seizure control, patients may be monitored through pharmacokinetic assessments to ensure efficacy of the ARV regimen (Level C).”


http://www.dailyrx.com/seizure-drugs-hiv-aids-patients-have-new-aan-guidelines

ANTI EPILEPSY DRUG PRESERVES BRAIN FUNCTION AFTER STROKE

New research suggests that an already-approved drug could dramatically reduce the debilitating impact of strokes, which affect nearly a million Americans every year.

In the study, one dose of the anti-epilepsy drug, retigabine, preserved brain tissue in a mouse model of stroke and prevented the loss of balance control and motor coordination. Researchers from the School of Medicine at The University of Texas Health Science Center at San Antonio conducted the study, which was published Feb. 3 in The Journal of Neuroscience.

Balance and coordination test

Hours after a stroke, both treated mice and a control group of mice were placed on a balance beam to observe motor coordination. The untreated mice displayed a pronounced loss of coordination with slips and falls. Treated mice had no difficulty with balance, ambulation or turning around on the beam.

"You couldn't even tell they had a stroke," said senior author Mark S. Shapiro, Ph.D., professor of physiology at the UT Health Science Center San Antonio. "They ran across the balance beam like gymnasts."

Histological analysis of the brain tissue of treated mice showed significantly reduced damage to the tissue after the stroke, compared to untreated mice. The protective effects of the medication were observed in treated mice up to five days after the stroke, said Sonya Bierbower, Ph.D., postdoctoral fellow and lead author of the report.

Duration of effect

Future studies will assess how long brain function can be protected after a stroke, and whether injury-related seizures can be prevented. "We are also going to see if we can prevent strokes in high-risk animal models," Dr. Bierbower said.

Retigabine and similar agents open specific proteins called potassium ion channels, whose action stops the electrical activity of nerve cells in the brain. The San Antonio team studied ischemic stroke, in which oxygen and nutrients are suddenly cut off due to a clot in a blood vessel. This is the type of stroke most often seen in humans. "We thought if we could stop the neurons from firing, stopping their electrical activity, we could conserve their resources until the time their blood supply was restored," Dr. Shapiro said. "This proved to be the case."

Cells starved of oxygen and nutrients for six hours are compromised and the process of dying is nearly impossible to reverse. Moreover, when cells die, they release factors that trigger many types of responses including an inflammatory response, leading to more cell death in the areas around the blood clot.

tPA for clots

A drug called tissue plasminogen activator (tPA) treats stroke by dissolving clots to restore blood flow, but this has significant limitations. tPA causes severe thinning of the blood, so it is not an option for patients who have high blood pressure, a history of bleeding or weak blood vessels. tPA is most effective in the first hours after a stroke, but its later use may do more damage than good.

Directly affecting nerve cells

Potassium channel openers such as retigabine work on a completely different system. "They have nothing to do with thinning blood, but preserving cells by putting a brake on their electrical activity," Dr. Shapiro said.

"It's treating the first step in the sequence and stopping the more damaging secondary effects," Dr. Bierbower said. "These agents directly affect the nerve cells themselves."

FDA approved for epilepsy

Because retigabine is approved by the U.S. Food and Drug Administration under the American brand name Ezogabine as an anticonvulsant, physicians may use it off label in stroke patients. FDA approval for specifically this drug as stroke therapy will require a clinical trial to be conducted, and a team of neurologists and neurosurgeons at the Health Science Center is considering it, Dr. Shapiro said.

"As a leading cause of death and disability, stroke poses a major risk to our society," said David F. Jimenez, M.D., FACS, professor and chairman of the Department of Neurosurgery at the Health Science Center. "It is very exciting to see that our collaborative work with our colleagues in physiology could provide a superb way to ameliorate the harmful effects of stroke on our patients."

Anti Muscarinics New Wonder Drugs For Neuropathy Or The Latest In A Long Line Of Nice Tries!

Today's post from painnewsnetwork.org (see link below) is one of a series of current articles all across the net about a potentially very effective new treatment for neuropathy. The difference between this one and the rest is that you can understand it, so kudos to the author for having 'translated' complex science into a language we can all understand. The article looks at a new development and study (still, unfortunately, at the rodent testing stage) aimed at blocking sensory nerves with medication, in order to cut out pain signals to the brain. By using the drug Pirenzepine (currently used to treat various conditions including Parkinson's) it is said that nerve growth and repair can be stimulated and that in itself is something new! If this drug is also effective on humans, it could provide a major breakthrough in the treatment of neuropathy. So many articles about this family of drugs are popping up that you get the feeling that serious people are seriously excited about it. Let's hope it all works out as it's meant to but scientists will have to accept that neuropathy patients have been here before and skepticism is more the order of the day than optimism. Nevertheless, it sounds very promising indeed. Remember that name...Pirenzepine.

Medication Could Reverse Peripheral Neuropathy  
By Pat Anson, Editor January 19, 2017

Blocking a sensory nerve signal with medication could prevent or even reverse symptoms of peripheral neuropathy, according to new research published in the Journal of Clinical Investigation.

About 20 million Americans suffer from peripheral neuropathy, which often causes a painful stinging or burning sensation in the hands or feet.


"Peripheral neuropathy is a major and largely untreated cause of human suffering," said lead author Nigel Calcutt, PhD, a professor of pathology at the University of California San Diego School of Medicine. "It has huge associated health care costs."

In studies on diabetic laboratory rats, Calcutt and his colleagues identified a molecular signaling pathway that, when blocked with the drug pirenzepine, promotes sensory neuron growth and prevents or reverses the nerve damage caused by peripheral neuropathy.

The discovery suggests that pirenzepine and other anti-muscarinic drugs – a class of nerve medication that is already used to treat Parkinson’s disease, motion sickness, irritable bowel syndrome and other conditions – could be used as a new treatment for peripheral neuropathy.

"This is encouraging because the safety profile of anti-muscarinic drugs is well-characterized, with more than 20 years of clinical application for a variety of indications in Europe," said senior study author Paul Fernyhough, PhD, a professor in the departments of pharmacology and therapeutics and physiology at the University of Manitoba in Canada. "The novel therapeutic application of anti-muscarinic antagonists suggested by our studies could potentially translate relatively rapidly to clinical use."

The first symptoms of peripheral neuropathy are usually a tingling or numbing sensation in the toes, feet, and hands caused by small fiber nerve damage. The symptoms progress, spread and become more painful, dramatically affecting quality of life.

Researchers say treating the disease in its early stages is key.

“Since small fiber degeneration develops early in the human disease and can be reliably quantified using a variety of minimal or noninvasive techniques that can be applied iteratively, future clinical trials of anti-muscarinic drugs might feasibly focus on reversal of these early indices of neuropathy,” they said.

“Further, as anti-muscarinic drugs were effective in augmenting collateral (nerve) sprouting in our in vitro assay, this new therapeutic approach may be most effective during the early stages of a dying-back neuropathy prior to overt and/or complete fiber loss.”

Nearly 26 million people in the United States have diabetes and about half have some form of neuropathy, according to the American Diabetes Association. Small fiber neuropathy can also be caused by lupus, HIV, Lyme disease, celiac disease or chemotherapy.

https://www.painnewsnetwork.org/stories/2017/1/19/medication-could-reverse-peripheral-neuropathy

Anti Epilepsy Drugs Control Nerve Pain

Today's post from mayoclinic.org (see link below) is very useful for those already taking anti-epilepsy drugs for their neuropathy, or those for whom that may become an option in the future. Many people are confused and more than a little alarmed as to why they're being given anti-seizure drugs for nerve damage. This article explains the reasoning behind prescribing those drugs for neuropathy. As you look through the list below, you'll probably recognise some of the drugs from your other research into the disease. The fact is, nobody is totally certain why anti-seizure drugs work for nerve pain (in some cases, not all and side-effects are an issue!) but it's clear that they block pain signals sufficiently to be effective. Worth a read.
 

Anti-seizure medications: Relief from nerve pain By Mayo Clinic Staff

 Anti-seizure drugs often are used to help control the type of pain caused by damaged nerves.

Anti-seizure medications were originally designed to treat people with epilepsy. But the nerve-calming qualities of some of these medications can also help quiet the burning, stabbing or shooting pain often caused by nerve damage. 

Why does it hurt?

Nerves can be damaged by many things, including injury, surgery, disease or exposure to toxins. The damaged nerves are activated inappropriately and send pain signals that don't serve a useful purpose. This type of pain can be debilitating and difficult to control.

Nerve damage (neuropathy) can be caused by many conditions, including:
Diabetes. High blood sugar levels, common in diabetes, can damage nerves throughout your body. The first symptom generally is numbness and pain in your hands and feet (diabetic neuropathy).
Shingles. Anyone who has had chickenpox is at risk of shingles, a rash of blisters that can be painful or itchy. A condition called postherpetic neuralgia occurs if shingles pain persists after the rash disappears.
Because the risk of shingles increases with age, everyone age 50 and older should receive the varicella-zoster virus vaccine (Zostavax), which can help prevent this painful condition.

Chemotherapy. Some chemotherapy drugs can damage nerves, causing pain and numbness that generally begin in the tips of your toes and fingers (neuropathy).
Herniated disk. Nerve damage can occur if a herniated disk in your spine squeezes a nerve passing through your vertebrae too tightly.
Fibromyalgia. Fibromyalgia is a chronic condition that causes pain and tenderness throughout your body. 

How do anti-seizure drugs help?

The exact mechanism of action isn't fully understood, but anti-seizure medications appear to interfere with the overactive transmission of pain signals sent from damaged nerves.

Some anti-seizure drugs work particularly well for certain conditions. Carbamazepine (Carbatrol, Tegretol) is widely prescribed for trigeminal neuralgia, a condition that causes searing facial pain that feels like an electric shock.

It's important to note that the Food and Drug Administration has issued a warning that all anti-seizure medications are associated with a slightly increased risk of suicidal thoughts or actions. Talk to a doctor or counselor promptly if you feel depressed or suicidal.
 
Newer anti-seizure drugs may have fewer side effects

More recent research supports the use of the anticonvulsants gabapentin (Neurontin) or pregabalin (Lyrica) to help relieve pain caused by damaged nerves.

Both gabapentin and pregabalin are particularly effective in the treatment of postherpetic neuralgia, diabetic neuropathy and pain caused by a spinal cord injury. Pregabalin also may be used to treat fibromyalgia.

Because these drugs have few side effects and are usually well tolerated, they are often the first medications to try for neuropathic pain. You may experience side effects, such as drowsiness, dizziness, confusion or swelling in the feet and legs. These side effects are limited by starting with a low dosage and slowly increasing it.

Medications from other drug classes with distinct mechanisms of pain relief (such as antidepressants) may be used in combination with anti-seizure class medications if anti-seizure medications fail to control your pain. 

Side effects limit use of older anticonvulsants

Anti-seizure drugs have been used to treat nerve pain for many years, but their use was limited by the severity of side effects they produce.

Older anti-seizure drugs include:
Carbamazepine (Carbatrol, Tegretol)
Oxcarbazepine (Trileptal)
Phenytoin (Dilantin)
Valproic acid (Depakene)

Side effects may include:
Liver damage
Nausea
Vomiting
Double vision
Loss of coordination
Drowsiness
Headache

If you take an older anticonvulsant, you generally need regular follow-up visits so that your doctor can monitor for side effects. These older drugs often have more side effects than do the newer anticonvulsants, and the evidence supporting use of the older anticonvulsants for neuropathic pain is sparse at times. As a result, older drugs may be recommended only when the newer medications prove ineffective. 

Research continues

As scientists learn more about the way anti-seizure drugs work, this information will be useful in determining which drugs may work best for different types of nerve pain. Pain caused by nerve damage can be disabling, but anti-seizure drugs sometimes provide relief.

http://www.mayoclinic.org/diseases-conditions/peripheral-neuropathy/in-depth/pain-medications/art-20045004