Neuropathic pain


Neuropathic pain

Neuropathic pain results from lesions or diseases affecting the somatosensory system.[1] It may be associated with abnormal sensations called dysesthesia, which occur spontaneously and allodynia that occurs in response to external stimuli. Neuropathic pain may have continuous and/or episodic (paroxysmal) components. The latter are likened to an electric shock. Common qualities include burning or coldness, "pins and needles" sensations, numbness and itching. Nociceptive pain, by contrast, is more commonly described as aching.

Up to 7% to 8% of the European population is affected and in 5% of persons it may be severe.[2][3] Neuropathic pain may result from disorders of the peripheral nervous system or the central nervous system (brain and spinal cord). Thus, neuropathic pain may be divided into peripheral neuropathic pain, central neuropathic pain, or mixed (peripheral and central) neuropathic pain.

Cause

Central neuropathic pain is found in spinal cord injury, multiple sclerosis, and some strokes. Fibromyalgia, a disorder of chronic widespread pain, is potentially a central pain disorder and is responsive to medications that are effective for neuropathic pain.[4] Aside from diabetes (see diabetic neuropathy) and other metabolic conditions, the common causes of painful peripheral neuropathies are herpes zoster infection, HIV-related neuropathies, nutritional deficiencies, toxins, remote manifestations of malignancies, genetic (gene HCN2),[5] and immune mediated disorders or physical trauma to a nerve trunk.[6][7] Neuropathic pain is common in cancer as a direct result of cancer on peripheral nerves (e.g., compression by a tumor), or as a side effect of chemotherapy,[8][9] radiation injury or surgery.

Mechanisms

The starting point for neuropathic pain is a lesion or dysfunction within the somatosensory system. Current knowledge regarding the mechanisms of neuropathic pain is incomplete and is biased by a focus on animal models of peripheral nerve injury.

Peripheral

Under normal circumstances, pain sensations are carried by unmyelinated and thinly myelinated nerve fibers, designated C-fibers and A-delta fibers, respectively. After a peripheral nerve lesion, aberrant regeneration may occur. Neurons become unusually sensitive and develop spontaneous pathological activity, abnormal excitability, and heightened sensitivity to chemical, thermal and mechanical stimuli. This phenomenon is called "peripheral sensitization".

Central

The (spinal cord) dorsal horn neurons give rise to the spinothalamic tract (STT), which constitutes the major ascending nociceptive pathway. As a consequence of ongoing spontaneous activity arising in the periphery, STT neurons develop increased background activity, enlarged receptive fields and increased responses to afferent impulses, including normally innocuous tactile stimuli. This phenomenon is called central sensitization. Central sensitization is an important mechanism of persistent neuropathic pain.

Other mechanisms, however, may take place at the central level after peripheral nerve damage. The loss of afferent signals induces functional changes in dorsal horn neurons. A decrease in the large fiber input decreases activity of interneurons inhibiting nociceptive neurons i.e. loss of afferent inhibition. Hypoactivity of the descending antinociceptive systems or loss of descending inhibition may be another factor. With loss of neuronal input (deafferentation) the STT neurons begin to fire spontaneously, a phenomenon designated "deafferentation hypersensitivity.”

Neuroglia ("glial cells") may play a role in central sensitization. Peripheral nerve injury induces glia to release proinflammatory cytokines and glutamate which, in turn influence neurons.[10]

Mechanisms at light-microscopic and submicroscopic levels

The phenomenon described above are dependent on changes at light-microscopic and submicroscopic levels. Altered expression of ion channels, changes in neurotransmitters and their receptors as well as altered gene expression in response to neural input are at play.[11]

Treatments

Neuropathic pain can be very difficult to treat with only some 40-60% of patients achieving partial relief.[12]

In addition to the work of Dworkin, O'Connor and Backonja et al., cited above, there have been several recent attempts to derive guidelines for pharmacological therapy.[13][14][15] These have combined evidence from randomized controlled trials with expert opinion.

Determining the best treatment for individual patients remains challenging. Attempts to translate scientific studies into best practices are limited by factors such as differences in reference populations and a lack of head-to-head studies. Furthermore, multi-drug combinations and the needs of special populations, such as children, require more study.

It is common practice in medicine to designate classes of medication according to their most common or familiar use e.g. as "antidepressants" and "anti-epileptic drugs" (AED's). These drugs have alternate uses to treat pain because the human nervous system employs common mechanisms for different functions, for example ion channels for impulse generation and neurotransmitters for cell-to-cell signaling.

Favored treatments are certain antidepressants e.g. tricyclics and selective serotonin-norepinephrine reuptake inhibitors (SNRI's), anticonvulsants, especially pregabalin (Lyrica) and gabapentin (Neurontin), and topical lidocaine. Opioid analgesics and tramadol are recognized as useful agents but are not recommended as first line treatments. Many of the pharmacologic treatments for chronic neuropathic pain decrease the sensitivity of nociceptive receptors, or desensitize C fibers such that they transmit fewer signals.

Some drugs may exert their influence through descending pain modulating pathways. These descending pain modulating pathways originate in the brainstem.

Antidepressants

The functioning of antidepressants is different in neuropathic pain from that observed in depression. Activation of descending norepinephrinergic and serotonergic pathways to the spinal cord limit pain signals ascending to the brain. Antidepressants will relieve neuropathic pain in non-depressed persons.

In animal models of neuropathic pain it has been found that compounds which only block serotonin reuptake do not improve neuropathic pain.[16][17][18][19][20][21][22][23] Similarly, compounds that only block norepinephrine reuptake also do not improve neuropathic pain. Dual serotonin-norepinephrine reuptake inhibitors such as duloxetine, venlafaxine, and milnacipran, as well as tricyclic antidepressants such as nortriptyline and desipramine improve neuropathic pain and are considered first-line medications for this condition.[15]

Bupropion has been found to have efficacy in the treatment of neuropathic pain.[24][25][26]

Tricyclic antidepressants may also have effects on sodium channels.

Anticonvulsants

Pregabalin (Lyrica) and gabapentin (Neurontin) work by blocking specific calcium channels on neurons and are preferred first-line medications for diabetic neuropathy. The anticonvulsants carbamazepine (Tegretol) and oxcarbazepine (Trileptal) are especially effective in trigeminal neuralgia. The actions of these two drugs are medicated principally through sodium channels.

Lamotrigine may have a special role in treating two conditions for which there are few alternatives, namely post stroke pain and HIV/AIDS-related neuropathy in patients already receiving antiretroviral therapy.[27]

Opioids

Opioids, also known as narcotics, are increasingly recognized as important treatment options for chronic pain. They are not considered first line treatments in neuropathic pain but remain the most consistently effective class of drugs for this condition. Opioids must be used only in appropriate individuals and under close medical supervision.

Several opioids, particularly methadone, and ketobemidone possess NMDA antagonism in addition to their µ-opioid agonist properties. Methadone does so because it is a racemic mixture; only the l-isomer is a potent µ-opioid agonist. The d-isomer does not have opioid agonist action and acts as an NMDA antagonist; d-methadone is analgesic in experimental models of chronic pain.[28] Clinical studies are in progress to test the efficacy of d-methadone in neuropathic pain syndromes.

There is little evidence to indicate that one strong opioid is more effective than another. Expert opinion leans toward the use of methadone for neuropathic pain, in part because of its NMDA antagonism. It is reasonable to base the choice of opioid on other factors.[29]

Topical agents

In some forms of neuropathy, especially post-herpetic neuralgia, the topical application of local anesthetics such as lidocaine can provide relief. A transdermal patch containing lidocaine is available commercially in some countries.

Repeated topical applications of capsaicin, are followed by a prolonged period of reduced skin sensibility referred to as desensitization, or nociceptor inactivation. Capsaicin not only depletes substance P but also results in a reversible degeneration of epidermal nerve fibers.[30] Nevertheless, benefits appear to be modest with standard (low) strength preparations.[31]

Cannabinoids

Marijuana's active ingredients are called cannabinoids. Unfortunately, strongly held beliefs make discussion of the appropriate use of these substances, in a medical context, difficult.[32] Similar considerations apply to opioids.

A recent study showed smoked marijuana is beneficial in treating symptoms of HIV-associated peripheral neuropathy.[33] Nabilone is an artificial cannabinoid which is significantly more potent than delta-9-tetrahydrocannabinol (THC). Nabilone produces less relief of chronic neuropathic pain and had slightly more side effects than dihydrocodeine.[34]

The predominant adverse effects are CNS depression and cardiovascular effects which are mild and well tolerated but, psychoactive side effects limit their use.[35] A complicating issue may be a narrow therapeutic window; lower doses decrease pain but higher doses have the opposite effect.[36]

Sativex, a fixed dose combination of delta-9-tetrahydrocannabinol (THC) and cannabidiol, is sold as an oromucosal spray. The product is approved in Canada as adjunctive treatment for the symptomatic relief of neuropathic pain in multiple sclerosis, and for cancer related pain.[37]

Long-term studies are needed to assess the probability of weight gain,[38] unwanted psychological influences and other adverse effects.

Botulinum toxin type A

Botulinum toxin type A (BTX-A) is best know by its trade name, Botox. Local intradermal injection of BTX-A is helpful in chronic focal painful neuropathies. The analgesic effects are not dependent on changes in muscle tone. Benefits persist for at least 14 weeks from the time of administration.[39]

The utility of BTX-A in other painful conditions remains to be established.[40]

NMDA antagonism

The N-methyl-D-aspartate (NMDA) receptor seems to play a major role in neuropathic pain and in the development of opioid tolerance. Dextromethorphan is an NMDA antagonist at high doses. Experiments in both animals and humans have established that NMDA antagonists such as ketamine and dextromethorphan can alleviate neuropathic pain and reverse opioid tolerance.[41] Unfortunately, only a few NMDA antagonists are clinically available and their use is limited by a very short half life (dextrometorphan), weak activity (memantine)or unacceptable side effects (ketamine).

Reducing sympathetic nervous stimulation

In some neuropathic pain syndromes, "crosstalk" occurs between descending sympathetic nerves and ascending sensory nerves. Increases in sympathetic nervous system activity result in an increase of pain; this is known as sympathetically-mediated pain.

Lesioning operations on the sympathetic branch of the autonomic nervous system are sometimes carried out.

There are methods of treating sympathetically maintained pain in peripheral tissues. This is done topically to a patient having sympathetically maintained pain at a peripheral site where the pain originates. Wherein the sympathetically maintained pain can be diagnosed by local anesthetic blockade of the appropriate sympathetic ganglion or adrenergic receptor blockade via intravenous administration of phentolamine, and rekindled by intradermal injection of norepinephrine.[42]

Dietary supplements

There are two dietary supplements that have clinical evidence showing them to be effective treatments of diabetic neuropathy; alpha lipoic acid and benfotiamine.[43]

A 2007 review of studies found that injected (parenteral) administration of alpha lipoic acid (ALA) was found to reduce the various symptoms of peripheral diabetic neuropathy.[44] While some studies on orally administered ALA had suggested a reduction in both the positive symptoms of diabetic neuropathy (including stabbing and burning pain) as well as neuropathic deficits (paresthesia),[45] the metanalysis showed "more conflicting data whether it improves sensory symptoms or just neuropathic deficits alone".[44] There is some limited evidence that ALA is also helpful in some other non-diabetic neuropathies.[46]

Benfotiamine is a lipid-soluble form of thiamine that has several placebo-controlled double-blind trials proving efficacy in treating neuropathy and various other diabetic comorbidities.[47][48]

Other modalities

In addition to pharmacological treatment several other modalities are commonly recommended.[49] While lacking adequate double blind trials, these have shown to reduce pain and improve patient quality of life for chronic neuropathic pain: chiropractic, yoga, massage, meditation, cognitive therapy,[50] and prescribed exercise. Some pain management specialists will try acupuncture, with variable results.

Transcutaneous electrical nerve stimulation (TENS) may be worth considering in chronic neurogenic pain. TENS, with certain electrical waveforms, appears to have an acupuncture-like function.[citation needed]

Infrared photo therapy has been clinically proven to treat neuropathic pain and symptoms.[51][52] However, recent work has cast doubt on the value of this approach.[53]

Neuromodulators

Neuromodulation is a field of science, medicine and bioengineering that encompasses both implantable and non-implantable technologies (electrical and chemical) for treatment purposes.[54]

Implanted devices are expensive and carry the risk of complications. Available studies have focused on conditions having a different prevalence than neuropathic pain patients in general. More research is needed to define the range of conditions for which they might be beneficial.

Spinal cord stimulators and implanted spinal pumps

Spinal cord stimulators, use electrodes placed adjacent to, but outside the spinal cord. The overall complication rate is one-third, most commonly due to lead migration or breakage but advancements in the past decade have driven complication rates much lower. Lack of pain relief occasionaly prompts device removal.[55]

Infusion pumps deliver medication directly to the fluid filled (subarachnoid) space surrounding the spinal cord. Opioids alone or opioids with adjunctive medication (either a local anesthetic or clonidine) or more recently ziconotide[56] are infused. Complications such as, serious infection (meningitis), urinary retention, hormonal disturbance and intrathecal granuloma formation have been noted with intrathecal insufion.

There are no randomized studies of infusion pumps. For selected patients 50% or greater pain relief is achieved in 38% to 56% at six months but declines with the passage of time.[57] These results must be viewed skeptically since placebo effects cannot be evaluated.

Motor cortex stimulation

Stimulation of the primary motor cortex through electrodes placed within the skull but outside the thick meningeal membrane (dura) has been used to treat pain. The level of stimulation is below that for motor stimulation. As compared with spinal stimulation, which requires a noticeable tingling (paresthesia) for benefit, the only palpable effect is pain relief.[58][59]

Deep brain stimulation

The best long-term results with deep brain stimulation have been reported with targets in the periventricular/periaqueductal grey matter (79%), or the periventricular/periaqueductal grey matter plus thalamus and/or internal capsule (87%).[60] There is a significant complication rate which increase over time.[61]


References

  1. ^ "www.iasp-pain.org". http://www.iasp-pain.org/AM/Template.cfm?Section=Home&Template=/CM/ContentDisplay.cfm&ContentID=12215. Retrieved 11 December 2010. 
  2. ^ Torrance N, Smith BH, Bennett MI, Lee AJ (April 2006). "The epidemiology of chronic pain of predominantly neuropathic origin. Results from a general population survey". J Pain 7 (4): 281–9. doi:10.1016/j.jpain.2005.11.008. PMID 16618472. 
  3. ^ Bouhassira D, Lantéri-Minet M, Attal N, Laurent B, Touboul C (June 2008). "Prevalence of chronic pain with neuropathic characteristics in the general population". Pain 136 (3): 380–7. doi:10.1016/j.pain.2007.08.013. PMID 17888574. 
  4. ^ Dworkin RH, Fields HL (2005). "Fibromyalgia from the perspective of neuropathic pain". J Rheumatol Suppl 75: 1–5. PMID 16078355. http://www.jrheum.com/subscribers/05/75/1.html. 
  5. ^ http://timesofindia.indiatimes.com/home/science/Gene-find-may-lead-to-pills-that-kill-chronic-pain/articleshow/9930852.cms
  6. ^ Portenoy RK (1989). "Painful polyneuropathy". Neurol Clin 7 (2): 265–88. PMID 2566901. 
  7. ^ Vaillancourt PD, Langevin HM (1999). "Painful peripheral neuropathies". Med. Clin. North Am. 83 (3): 627–42, vi. doi:10.1016/S0025-7125(05)70127-9. PMID 10386118. 
  8. ^ [1] Chemotherapy-induced Peripheral Neuropathy Fact Sheet, Retrieved on 29 December 2008
  9. ^ [2] Cancerbackup, Macmillan Cancer Support, Peripheral neuropathy, Retrieved on 29 December 2008
  10. ^ Wieseler-Frank J, Maier SF, Watkins LR (2005). "Central proinflammatory cytokines and pain enhancement". Neuro-Signals 14 (4): 166–74. doi:10.1159/000087655. PMID 16215299. 
  11. ^ Truini A, Cruccu G (May 2006). "Pathophysiological mechanisms of neuropathic pain". Neurol. Sci. 27 Suppl 2: S179–82. doi:10.1007/s10072-006-0597-8. PMID 16688626. 
  12. ^ Dworkin RH, O'Connor AB, Backonja M, et al. (2007). "Pharmacologic management of neuropathic pain: evidence-based recommendations". Pain 132 (3): 237–51. doi:10.1016/j.pain.2007.08.033. PMID 17920770. 
  13. ^ Attal N, Cruccu G, Haanpää M, et al. (2006). "EFNS guidelines on pharmacological treatment of neuropathic pain". Eur. J. Neurol. 13 (11): 1153–69. doi:10.1111/j.1468-1331.2006.01511.x. PMID 17038030. 
  14. ^ Moulin DE, Clark AJ, Gilron I, et al. (2007). "Pharmacological management of chronic neuropathic pain - consensus statement and guidelines from the Canadian Pain Society". Pain Res Manag 12 (1): 13–21. PMC 2670721. PMID 17372630. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2670721. 
  15. ^ a b Robert H. Dworkin, PhD et al (2010). "Recommendations for the Pharmacological Management of Neuropathic Pain: An Overview and Literature Update". Mayo Clin Proc 85 (3): S3–S14. doi:10.4065/mcp.2009.0649. PMC 2844007. PMID 20194146. http://www.mayoclinicproceedings.com/content/85/3_suppl/S3.abstract. 
  16. ^ Bennett G, Xie Y (1988). "A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man". Pain 33 (1): 87–107. doi:10.1016/0304-3959(88)90209-6. PMID 2837713. 
  17. ^ Seltzer Z, Dubner R, Shir Y (1990). "A novel behavioral model of neuropathic pain disorders produced in rats by partial sciatic nerve injury". Pain 43 (2): 205–18. doi:10.1016/0304-3959(90)91074-S. PMID 1982347. 
  18. ^ Kim S, Chung J (1992). "An experimental model for peripheral neuropathy produced by segmental spinal nerve ligation in the rat". Pain 50 (3): 355–63. doi:10.1016/0304-3959(92)90041-9. PMID 1333581. 
  19. ^ Malmberg A, Basbaum A (1998). "Partial sciatic nerve injury in the mouse as a model of neuropathic pain: behavioral and neuroanatomical correlates". Pain 76 (1-2): 215–22. doi:10.1016/S0304-3959(98)00045-1. PMID 9696476. 
  20. ^ Sung B, Na H, Kim Y, Yoon Y, Han H, Nahm S, Hong S (1998). "Supraspinal involvement in the production of mechanical allodynia by spinal nerve injury in rats". Neurosci. Lett. 246 (2): 117–9. doi:10.1016/S0304-3940(98)00235-3. PMID 9627194. 
  21. ^ Lee B, Won R, Baik E, Lee S, Moon C (2000). "An animal model of neuropathic pain employing injury to the sciatic nerve branches". Neuroreport 11 (4): 657–61. doi:10.1097/00001756-200003200-00002. PMID 10757496. 
  22. ^ Decosterd I, Woolf C (2000). "Spared nerve injury: an animal model of persistent peripheral neuropathic pain". Pain 87 (2): 149–58. doi:10.1016/S0304-3959(00)00276-1. PMID 10924808. 
  23. ^ Vadakkan K, Jia Y, Zhuo M (2005). "A behavioral model of neuropathic pain induced by ligation of the common peroneal nerve in mice". The journal of pain: official journal of the American Pain Society 6 (11): 747–56. doi:10.1016/j.jpain.2005.07.005. PMID 16275599. 
  24. ^ Semenchuk MR, Davis B (March 2000). "Efficacy of sustained-release bupropion in neuropathic pain: an open-label study". The Clinical Journal of Pain 16 (1): 6–11. doi:10.1097/00002508-200003000-00002. PMID 10741812. http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?issn=0749-8047&volume=16&issue=1&spage=6. 
  25. ^ Semenchuk MR, Sherman S, Davis B (November 2001). "Double-blind, randomized trial of bupropion SR for the treatment of neuropathic pain". Neurology 57 (9): 1583–8. PMID 11706096. http://www.neurology.org/cgi/pmidlookup?view=long&pmid=11706096. 
  26. ^ Shah TH, Moradimehr A (February 2010). "Bupropion for the Treatment of Neuropathic Pain". The American Journal of Hospice & Palliative Care 27 (5): 333–6. doi:10.1177/1049909110361229. PMID 20185402. http://ajh.sagepub.com/cgi/pmidlookup?view=long&pmid=20185402. 
  27. ^ Wiffen PJ, Rees J. Lamotrigine for acute and chronic pain. Cochrane Database Syst Rev. 2007;(2):CD006044.
  28. ^ Davis AM, Inturrisi CE (1999). "d-Methadone blocks morphine tolerance and N-methyl-D-aspartate-induced hyperalgesia". J. Pharmacol. Exp. Ther. 289 (2): 1048–53. PMID 10215686. http://jpet.aspetjournals.org/cgi/content/full/289/2/1048. 
  29. ^ Bruera E, Palmer JL, Bosnjak S, et al. (2004). "Methadone versus morphine as a first-line strong opioid for cancer pain: a randomized, double-blind study". J. Clin. Oncol. 22 (1): 185–92. doi:10.1200/JCO.2004.03.172. PMID 14701781. 
  30. ^ Nolano M, Simone DA, Wendelschafer-Crabb G, Johnson T, Hazen E, Kennedy WR (1999). "Topical capsaicin in humans: parallel loss of epidermal nerve fibers and pain sensation". Pain 81 (1-2): 135–45. doi:10.1016/S0304-3959(99)00007-X. PMID 10353501. 
  31. ^ Finnerup NB, Otto M, Jensen TS, Sindrup SH (2007). "An evidence-based algorithm for the treatment of neuropathic pain". MedGenMed 9 (2): 36. PMC 1994866. PMID 17955091. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1994866. 
  32. ^ Ponto LL (May 2006). "Challenges of marijuana research". Brain 129 (Pt 5): 1081–3. doi:10.1093/brain/awl092. PMID 16627464. 
  33. ^ Abrams D, Jay C, Shade S, Vizoso H, Reda H, Press S, Kelly M, Rowbotham M, Petersen K (2007). "Cannabis in painful HIV-associated sensory neuropathy: a randomized placebo-controlled trial". Neurology 68 (7): 515–21. doi:10.1212/01.wnl.0000253187.66183.9c. PMID 17296917. 
  34. ^ Frank B, Serpell MG, Hughes J, Matthews JN, Kapur D (2008). "Comparison of analgesic effects and patient tolerability of nabilone and dihydrocodeine for chronic neuropathic pain: randomised, crossover, double blind study". BMJ 336 (7637): 199–201. doi:10.1136/bmj.39429.619653.80. PMC 2213874. PMID 18182416. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2213874. 
  35. ^ Campbell FA, Tramèr MR, Carroll D, Reynolds DJ, Moore RA, McQuay HJ (2001). "Are cannabinoids an effective and safe treatment option in the management of pain? A qualitative systematic review". BMJ 323 (7303): 13–6. doi:10.1136/bmj.323.7303.13. PMC 34324. PMID 11440935. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=34324. 
  36. ^ Wallace M, Schulteis G, Atkinson JH, et al. (2007). "Dose-dependent effects of smoked cannabis on capsaicin-induced pain and hyperalgesia in healthy volunteers". Anesthesiology 107 (5): 785–96. doi:10.1097/01.anes.0000286986.92475.b7. PMID 18073554. 
  37. ^ "Sativex - Investigational Cannabis-Based Treatment for Pain and Multiple Sclerosis Drug Development Technology". www.drugdevelopment-technology.com. http://www.drugdevelopment-technology.com/projects/sativex/. Retrieved 2008-08-08. 
  38. ^ Vickers SP, Kennett GA (March 2005). "Cannabinoids and the regulation of ingestive behaviour". Curr Drug Targets 6 (2): 215–23. PMID 15777191. http://www.bentham-direct.org/pages/content.php?CDT/2005/. 
  39. ^ Ranoux D, Attal N, Morain F, Bouhassira D (September 2008). "Botulinum toxin type A induces direct analgesic effects in chronic neuropathic pain". Annals of neurology 64 (3): 274–83. doi:10.1002/ana.21427. PMID 18546285. 
  40. ^ Naumann M, So Y, Argoff CE, et al. (May 2008). "Assessment: Botulinum neurotoxin in the treatment of autonomic disorders and pain (an evidence-based review): report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology". Neurology 70 (19): 1707–14. doi:10.1212/01.wnl.0000311390.87642.d8. PMID 18458231. 
  41. ^ Nelson KA, Park KM, Robinovitz E, Tsigos C, Max MB (1997). "High-dose oral dextromethorphan versus placebo in painful diabetic neuropathy and postherpetic neuralgia". Neurology 48 (5): 1212–8. PMID 9153445. 
  42. ^ Campbell; James N., Compositions and methods of treatment of sympathetically maintained pain (1998).
  43. ^ Head KA (2006). "Peripheral neuropathy: pathogenic mechanisms and alternative therapies" (PDF). Altern Med Rev 11 (4): 294–329. PMID 17176168. http://www.thorne.com/altmedrev/.fulltext/11/4/294.pdf. 
  44. ^ a b Foster TS (2007). "Efficacy and safety of alpha-lipoic acid supplementation in the treatment of symptomatic diabetic neuropathy". Diabetes Educ 33 (1): 111–7. doi:10.1177/0145721706297450. PMID 17272797. "ALA appears to improve neuropathic symptoms and deficits when administered via parenteral supplementation over a 3-week period. Oral treatment with ALA appears to have more conflicting data whether it improves sensory symptoms or just neuropathic deficits alone." 
  45. ^ Ziegler D, Ametov A, Barinov A, et al. (2006). "Oral treatment with alpha-lipoic acid improves symptomatic diabetic polyneuropathy: the SYDNEY 2 trial". Diabetes Care 29 (11): 2365–70. doi:10.2337/dc06-1216. PMID 17065669. 
  46. ^ Patton LL, Siegel MA, Benoliel R, De Laat A (2007). "Management of burning mouth syndrome: systematic review and management recommendations". Oral Surg Oral Med Oral Pathol Oral Radiol Endod 103 Suppl: S39.e1–13. doi:10.1016/j.tripleo.2006.11.009. PMID 17379153. 
  47. ^ Stracke H, Lindemann A, Federlin K (1996). "A benfotiamine-vitamin B combination in treatment of diabetic polyneuropathy". Exp. Clin. Endocrinol. Diabetes 104 (4): 311–6. doi:10.1055/s-0029-1211460. PMID 8886748. 
  48. ^ Thornalley PJ (2005). "The potential role of thiamine (vitamin B(1)) in diabetic complications". Curr Diabetes Rev 1 (3): 287–98. doi:10.2174/157339905774574383. PMID 18220605. 
  49. ^ Chen H, Lamer TJ, Rho RH, et al. (2004). "Contemporary management of neuropathic pain for the primary care physician". Mayo Clin. Proc. 79 (12): 1533–45. doi:10.4065/79.12.1533. PMID 15595338. 
  50. ^ Kerns JW, White A, Nashelsky J, Sherman S (2006). "Does psychiatric treatment help patients with intractable chronic pain?". J Fam Pract 55 (3): 235–6. PMID 16510058. http://www.jfponline.com/Pages.asp?AID=3897. 
  51. ^ Burke T. "Part 9. How Light (Photo Energy) May Increase Local NO and Vasodilation". Nitric Oxide and Its Role in Health and Diabetes. Diabetes In Control. http://www.diabetesincontrol.com/burkearchive/nitricoxide9.shtml. Retrieved 2008-03-28. 
  52. ^ Burke T. "Infrared Photo Energy May Reduce Neuropathic Pain". Practical Pain Management. http://www.anodynetherapy.ca/files/Practical_Pain_Mgmt_JulAug07.pdf. Retrieved 2011-10-20. 
  53. ^ Lavery LA, Murdoch DP, Williams J, Lavery DC (2008). "Does anodyne light therapy improve peripheral neuropathy in diabetes? A double-blind, sham-controlled, randomized trial to evaluate monochromatic infrared photoenergy". Diabetes Care 31 (2): 316–21. doi:10.2337/dc07-1794. PMID 17977931. 
  54. ^ Krames ES. Neuromodulatory devices are part of our "Tools of the Trade". Pain Med 2006;7:S3-5.
  55. ^ Turner JA, Loeser JD, Deyo RA, Sanders SB (2004). "Spinal cord stimulation for patients with failed back surgery syndrome or complex regional pain syndrome: a systematic review of effectiveness and complications". Pain 108 (1-2): 137–47. doi:10.1016/j.pain.2003.12.016. PMID 15109517. 
  56. ^ Lynch SS, Cheng CM, Yee JL (2006). "Intrathecal ziconotide for refractory chronic pain". Ann Pharmacother 40 (7-8): 1293–300. doi:10.1345/aph.1G584. PMID 16849624. 
  57. ^ Turner JA, Sears JM, Loeser JD (2007). "Programmable intrathecal opioid delivery systems for chronic noncancer pain: a systematic review of effectiveness and complications". Clin J Pain 23 (2): 180–95. doi:10.1097/01.ajp.0000210955.93878.44. PMID 17237668. 
  58. ^ Brown JA, Pilitsis JG. Motor Cortex Stimulation Pain Medicine 2006; 7:S140.
  59. ^ Osenbach, R. Neurostimulation for the Treatment of Intractable Facial Pain Pain Medicine 2006; 7:S126
  60. ^ Bittar RG, Kar-Purkayastha I, Owen SL, et al. (2005). "Deep brain stimulation for pain relief: a meta-analysis". J Clin Neurosci 12 (5): 515–9. doi:10.1016/j.jocn.2004.10.005. PMID 15993077. 
  61. ^ Oh MY, Abosch A, Kim SH, Lang AE, Lozano AM (2002). "Long-term hardware-related complications of deep brain stimulation". Neurosurgery 50 (6): 1268–74; discussion 1274–6. doi:10.1097/00006123-200206000-00017. PMID 12015845. 

Wikimedia Foundation. 2010.

Look at other dictionaries:

  • neuropathic pain — noun Pain caused by damage to nerves or by damage to the brain, brainstem, or spinal cord …   Wiktionary

  • Pain tolerance — is the amount of pain that a person can withstand before breaking down emotionally and/or physically. Exposure to pain as tolerance booster It is widely believed that exposing yourself to painful stimuli will increase your pain tolerance i.e.… …   Wikipedia

  • Pain — This article is about physical pain. For pain in the broader sense, see Suffering. For other uses, see Pain (disambiguation). Pain A sports player in pain. ICD 10 R52 …   Wikipedia

  • neuropathic — Relating in any way to neuropathy. * * * neu·ro·path·ic .n(y)u̇r ə path ik adj of, relating to, characterized by, or being a neuropathy <neuropathic pain> <neuropathic disorders> neu·ro·path·i·cal·ly i k(ə )lē adv …   Medical dictionary

  • Neuropathic arthropathy — Charcot joint disease redirects here. For the nerve disease, see Charcot Marie Tooth disease. For Charcot s disease (Lou Gehrig s disease), see Amyotrophic lateral sclerosis. For several other diseases associated with Jean Martin Charcot, see… …   Wikipedia

  • Neuropathic joint disease — Infobox Disease Name = Neuropathic joint disease Caption = DiseasesDB = 2344 ICD10 = ICD9 = ICDO = OMIM = MedlinePlus = eMedicineSubj = orthoped eMedicineTopic = 381 eMedicine mult = eMedicine2|radio|476 MeshID = Neuropathic osteoarthropathy… …   Wikipedia

  • neuropathic arthritis — Charcot s joint an extreme form of osteoarthritis resulting from damage to the sensory nerves that supply a joint. Causes include diabetes mellitus (see diabetic neuropathy), tabes dorsalis, syringomyelia, leprosy, congenital insensitivity to… …   The new mediacal dictionary

  • Cancer pain — Pain is a symptom frequently associated with cancer. Cancer can cause pain by irritating or damaging nerves, by stimulating nociceptors (pain sensitive nerve fibers), or by releasing chemicals that make nociceptors respond to normally non painful …   Wikipedia

  • neurogenic pain — neuropathic pain pain, such as that occurring in causalgia or herpetic neuralgia, that results from direct stimulation of nervous tissue of the peripheral or central nervous system (except for sensitized C fibers), generally felt as burning or… …   Medical dictionary

  • Chronic pain — ICD 10 R52.1 R52.2 ICD 9 338.2 Chronic pain has several different meanings in medicine. Traditionally, the distinction betwe …   Wikipedia


Share the article and excerpts

Direct link
Do a right-click on the link above
and select “Copy Link”

We are using cookies for the best presentation of our site. Continuing to use this site, you agree with this.