ICD9 = ICD9|337.0-ICD9|337.1,
eMedicineSubj = search
eMedicineTopic = neuropathy
eMedicine_mult = | MeshID =
Neuropathy is a medical term, usually short for
peripheral neuropathy. Peripheral neuropathy is defined as deranged function and structure of peripheral motor, sensory, and autonomic neurons, involving either the entire neuron or selected levels.cite journal |author=Dyck PJ |title=Current concepts in neurology. The causes, classification, and treatment of peripheral neuropathy |journal=N. Engl. J. Med. |volume=307 |issue=5 |pages=283–6 |year=1982 |pmid=6283352 |doi=]
The four cardinal patterns of peripheral neuropathy are
polyneuropathy, mononeuropathy, mononeuritis multiplexand autonomic neuropathy. The most common form is (symmetrical) peripheral polyneuropathy, which mainly affects the feet and legs.
radiculopathy" involves spinal nerve roots, but if peripheral nerves are also involved the term radiculoneuropathy is used.
The form of neuropathy may be further broken down by cause, or the size of predominant fiber involvement, i.e. large fiber or
small fiber peripheral neuropathy. Frequently the cause of a neuropathy cannot be identified and it is designated idiopathic.
Neuropathy may be associated with varying combinations of weakness, autonomic changes and sensory changes. Loss of muscle bulk or fasciculations, a particular fine twitching of muscle may be seen. Sensory symptoms encompass loss of sensation and "positive" phenomena including pain (for a more detailed discussion, see
According to the most widely accepted definition, neuropathic pain is "initiated or caused by a primary lesion or dysfunction in the nervous system."cite book |author=Bogduk, Nikolai; Merskey, Harold |title=Classification of chronic pain: descriptions of chronic pain syndromes and definitions of pain terms |edition=2nd edition |publisher=IASP Press |location=Seattle |year=1994 |pages=212 |isbn=0931092051 |oclc= |doi=] As much as 7% to 8% of the of the population is affected and in 5% it may be severe. [cite journal |author=Torrance N, Smith BH, Bennett MI, Lee AJ |title=The epidemiology of chronic pain of predominantly neuropathic origin. Results from a general population survey |journal=J Pain |volume=7 |issue=4 |pages=281–9 |year=2006 |month=April |pmid=16618472 |doi=10.1016/j.jpain.2005.11.008 |url=] [cite journal |author=Bouhassira D, Lantéri-Minet M, Attal N, Laurent B, Touboul C |title=Prevalence of chronic pain with neuropathic characteristics in the general population |journal=Pain |volume=136 |issue=3 |pages=380–7 |year=2008 |month=June |pmid=17888574 |doi=10.1016/j.pain.2007.08.013 |url=] 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.
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 effective for neuropathic pain.cite journal |author=Dworkin RH, Fields HL |title=Fibromyalgia from the perspective of neuropathic pain |journal=J Rheumatol Suppl |volume=75 |issue= |pages=1–5 |year=2005 |pmid=16078355 |doi= |url=http://www.jrheum.com/subscribers/05/75/1.html]
Aside from diabetes (see
Diabetic neuropathy) and other metabolic conditions, the common causes of painful peripheral neuropathies are herpes zosterinfection, HIV-related neuropathies, nutritional deficiencies, toxins, remote manifestations of malignancies, genetic and immune mediated disorders.cite journal |author=Portenoy RK |title=Painful polyneuropathy |journal=Neurol Clin |volume=7 |issue=2 |pages=265–88 |year=1989 |pmid=2566901 |doi=] cite journal |author=Vaillancourt PD, Langevin HM |title=Painful peripheral neuropathies |journal=Med. Clin. North Am. |volume=83 |issue=3 |pages=627–42, vi |year=1999 |pmid=10386118| doi = 10.1016/S0025-7125(05)70127-9 ]
Neuropathic pain is common in
canceras a direct result of cancer on peripheral nerves (e.g., compression by a tumor), as a side effect of some chemotherapydrugs, and as a result of radiation injury.
Neuropathy often results in numbness, abnormal sensations called
dysesthesias and allodynias that occur either spontaneously or in reaction to external stimuli, and a characteristic form of pain, called neuropathic pain or neuralgia, that is qualitatively different from the ordinary nociceptive pain one might experience from stubbing a toe.
Neuropathic pain may have continuous and/or episodic (paroxysmal) components. The latter are likened to an electric shock. Common qualities of the pain include burning or coldness, "pins and needles" sensations, numbness and itching. "Ordinary" pain results from exclusive stimulation of pain fibers, while neuropathic pain often results from the firing of both pain and non-pain (touch, warm, cool) sensory nerve fibers serving the same area. The result is signals that the spinal cord and brain do not normally receive.
Mechanisms of neuropathic pain
The starting point for neuropathic pain is a lesion within the somatosensory system. Injured peripheral nerve fibers give rise to an intense and persistent input to the central nervous system, which, in some cases, induces secondary changes in the excitability of spinal cord, dorsal horn neurons. Current knowledge regarding the mechanisms of neuropathic pain is incomplete and is biased by a focus on animal models of peripheral nerve injury.
After a peripheral
nerve injury, a neuroma develops at the nerve stump. Regenerating C-fibresof damaged axons develop ongoing spontaneous activity, abnormal excitability and a heightened sensitivity to chemical, thermal and mechanical stimuli. This phenomenon is called "peripheral sensitization."
dorsal hornneurons giving rise to the spinothalamic tract(STT) neurons constitute the major ascending nociceptive pathway.
As a consequence of the ongoing spontaneous activity following activation of primary nociceptors, STT neurons develop an increased background activity, enlarged receptive field and increased responses to afferent impulses, including normally innocuous tactile stimuli. This phenomenon is called central sensitization. Central sensitization has been proposed as 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.”
Mechanisms at light-microscopic and submicroscopic levels
The phenomenon described above are dependent on changes at light-microscopic and submicroscopic levels. Aberrant regeneration, 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. [cite journal |author=Truini A, Cruccu G |title=Pathophysiological mechanisms of neuropathic pain |journal=Neurol. Sci. |volume=27 Suppl 2 |issue= |pages=S179–82 |year=2006 |month=May |pmid=16688626 |doi=10.1007/s10072-006-0597-8 |url=]
Treatments for neuropathic pain
Neuropathic pain can be very difficult to treat with only some 40-60% of patients achieving partial relief.cite journal |author=Dworkin RH, O'Connor AB, Backonja M, "et al" |title=Pharmacologic management of neuropathic pain: evidence-based recommendations |journal=Pain |volume=132 |issue=3 |pages=237–51 |year=2007 |pmid=17920770 |doi=10.1016/j.pain.2007.08.033]
Deciding on the best treatment for individual patients challenges both the art and science of medicine. Attempts to synthesize scientific studies into best practices are limited by such factors as differences in reference populations and a lack of head-to-head studies. Furthermore, there are few studies evaluating treatment combinations or the special needs of children.
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 channelsfor impulse generation and neurotransmitters for cell-to-cell signaling.
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.cite journal |author=Attal N, Cruccu G, Haanpää M, "et al" |title=EFNS guidelines on pharmacological treatment of neuropathic pain |journal=Eur. J. Neurol. |volume=13 |issue=11 |pages=1153–69 |year=2006 |pmid=17038030 |doi=10.1111/j.1468-1331.2006.01511.x] cite journal |author=Moulin DE, Clark AJ, Gilron I, "et al" |title=Pharmacological management of chronic neuropathic pain - consensus statement and guidelines from the Canadian Pain Society |journal=Pain Res Manag |volume=12 |issue=1 |pages=13–21 |year=2007 |pmid=17372630 |doi=] These have combined evidence from
randomized controlled trials with expert opinion.
Favored treatments are certain antidepressants e.g tricyclics and selective serotonin-norepinephrine re-uptake inhibitors (SNRI's),
anticonvulsants, especially pregabalin(Lyrica) and gabapentin(Neurontin), and topical lidocaine. Opioidanalgesics and tramadolare 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 fiberssuch that they transmit fewer signals.
Antidepressants function differently in neuropathic pain than 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. [cite journal |author=Bennett G, Xie Y |title=A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man |journal=Pain |volume=33 |issue=1 |pages=87–107 |year=1988 |pmid=2837713 | doi = 10.1016/0304-3959(88)90209-6 ] [cite journal |author=Seltzer Z, Dubner R, Shir Y |title=A novel behavioral model of neuropathic pain disorders produced in rats by partial sciatic nerve injury |journal=Pain |volume=43|pmid=1982347 | doi = 10.1016/0304-3959(90)91074-S ] [cite journal |author=Kim S, Chung J |title=An experimental model for peripheral neuropathy produced by segmental spinal nerve ligation in the rat |journal=Pain |volume=50 |issue=3 |pages=355–63 |year=1992 |pmid=1333581 |doi=10.1016/0304-3959(92)90041-9] [cite journal |author=Malmberg A, Basbaum A |title=Partial sciatic nerve injury in the mouse as a model of neuropathic pain: behavioral and neuroanatomical correlates |journal=Pain |volume=76 |issue=1-2 |pages=215–22 |year=1998 |pmid=9696476 | doi = 10.1016/S0304-3959(98)00045-1 ] [cite journal |author=Sung B, Na H, Kim Y, Yoon Y, Han H, Nahm S, Hong S |title=Supraspinal involvement in the production of mechanical allodynia by spinal nerve injury in rats |journal=Neurosci. Lett. |volume=246 |issue=2 |pages=117–9 |year=1998 |pmid=9627194 | doi = 10.1016/S0304-3940(98)00235-3 ] [cite journal |author=Lee B, Won R, Baik E, Lee S, Moon C |title=An animal model of neuropathic pain employing injury to the sciatic nerve branches |journal=Neuroreport |volume=11 |issue=4 |pages=657–61 |year=2000 |pmid=10757496 | doi = 10.1097/00001756-200003200-00002 ] [cite journal |author=Decosterd I, Woolf C |title=Spared nerve injury: an animal model of persistent peripheral neuropathic pain |journal=Pain |volume=87 |issue=2 |pages=149–58 |year=2000 |pmid=10924808 | doi = 10.1016/S0304-3959(00)00276-1 ] [cite journal |author=Vadakkan K, Jia Y, Zhuo M |title=A behavioral model of neuropathic pain induced by ligation of the common peroneal nerve in mice |journal=The journal of pain : official journal of the American Pain Society |volume=6 |issue=11 |pages=747–56 |year=2005 |pmid=16275599] Similarly, compounds that only block
norepinephrinereuptake also do not improve neuropathic pain. Compounds such as duloxetine, venlafaxine, and milnacipranthat block both serotoninreuptake and norepinephrine reuptake do improve neuropathic pain.
Tricyclic antidepressants may also work on sodium channels in peripheral nerves.
Pregabalin(Lyrica) and gabapentin(Neurontin) work by blocking specific calcium channels on neurons. The actions of the anticonvulsants carbamazepine(Tegretol) and oxcarbazepine(Trileptal), especially effective on trigeminal neuralgia, are principally on 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 neuropathyin that subgroup on antiretroviral therapy. [Wiffen PJ, Rees J. Lamotrigine for acute and chronic pain.Cochrane Database Syst Rev. 2007;(2):CD006044.]
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
methadonehave NMDA antagonist activity in addition to their µ-opioid agonist properties.
ketobemidonepossess NMDA antagonsism. Methadone does so because it is a racemicmixture; only the l-isomer is a potent µ-opioid agonist.cite journal |author=Davis AM, Inturrisi CE |title=d-Methadone blocks morphine tolerance and N-methyl-D-aspartate-induced hyperalgesia |journal=J. Pharmacol. Exp. Ther. |volume=289 |issue=2 |pages=1048–53 |year=1999 |pmid=10215686 |doi= |url=http://jpet.aspetjournals.org/cgi/content/full/289/2/1048]
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 NMDA antagonism. It is reasonable to base the choice of opioid on other factors.cite journal |author=Bruera E, Palmer JL, Bosnjak S, "et al" |title=Methadone versus morphine as a first-line strong opioid for cancer pain: a randomized, double-blind study |journal=J. Clin. Oncol. |volume=22 |issue=1 |pages=185–92 |year=2004 |pmid=14701781 |doi=10.1200/JCO.2004.03.172]
In some forms of neuropathy, especially post-herpes neuralgia, the topical application of local anesthetics such as
lidocainecan 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. cite journal |author=Nolano M, Simone DA, Wendelschafer-Crabb G, Johnson T, Hazen E, Kennedy WR |title=Topical capsaicin in humans: parallel loss of epidermal nerve fibers and pain sensation |journal=Pain |volume=81 |issue=1-2 |pages=135–45 |year=1999 |pmid=10353501| doi = 10.1016/S0304-3959(99)00007-X ] Nevertheless, benefits appear to be modest. cite journal |author=Finnerup NB, Otto M, Jensen TS, Sindrup SH |title=An evidence-based algorithm for the treatment of neuropathic pain |journal=MedGenMed |volume=9 |issue=2 |pages=36 |year=2007 |pmid=17955091 |doi=]
Marijuanaand its active ingredients are called cannabinoids. Unfortunately, strongly held beliefs make discussion of the appropriate use of these substances, in a medical context, difficult. [cite journal |author=Ponto LL |title=Challenges of marijuana research |journal=Brain |volume=129 |issue=Pt 5 |pages=1081–3 |year=2006 |month=May |pmid=16627464 |doi=10.1093/brain/awl092] Similar considerations apply to opioids.
A recent study showed smoked marijuana is beneficial in treating symptoms of
HIV-associated peripheral neuropathy.cite journal |author=Abrams D, Jay C, Shade S, Vizoso H, Reda H, Press S, Kelly M, Rowbotham M, Petersen K |title=Cannabis in painful HIV-associated sensory neuropathy: a randomized placebo-controlled trial |journal=Neurology |volume=68 |issue=7 |pages=515–21 |year=2007 |pmid=17296917 | doi = 10.1212/01.wnl.0000253187.66183.9c ] Nabiloneis 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.cite journal |author=Frank B, Serpell MG, Hughes J, Matthews JN, Kapur D |title=Comparison of analgesic effects and patient tolerability of nabilone and dihydrocodeine for chronic neuropathic pain: randomised, crossover, double blind study |journal=BMJ |volume=336 |issue=7637 |pages=199–201 |year=2008 |pmid=18182416 |doi=10.1136/bmj.39429.619653.80]
The predominant adverse effects are CNS depression and cardiovascular effects which are mild and well tolerated but, psychoactive side effects limit their use.cite journal |author=Campbell FA, Tramèr MR, Carroll D, Reynolds DJ, Moore RA, McQuay HJ |title=Are cannabinoids an effective and safe treatment option in the management of pain? A qualitative systematic review |journal=BMJ |volume=323 |issue=7303 |pages=13–6 |year=2001 |pmid=11440935| doi = 10.1136/bmj.323.7303.13 ] A complicating issue may be a narrow therapeutic window; lower doses decrease pain but higher doses have the opposite effect.cite journal |author=Wallace M, Schulteis G, Atkinson JH, "et al" |title=Dose-dependent effects of smoked cannabis on capsaicin-induced pain and hyperalgesia in healthy volunteers |journal=Anesthesiology |volume=107 |issue=5 |pages=785–96 |year=2007 |pmid=18073554 |doi=10.1097/01.anes.0000286986.92475.b7 |doi_brokendate=2008-06-25]
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 cancerrelated pain. [cite web
title=Sativex - Investigational Cannabis-Based Treatment for Pain and Multiple Sclerosis Drug Development Technology
Long-term studies are needed to assess the probability of weight gain [cite journal |author=Vickers SP, Kennett GA |title=Cannabinoids and the regulation of ingestive behaviour |journal=Curr Drug Targets |volume=6 |issue=2 |pages=215–23 |year=2005 |month=March |pmid=15777191 |doi= |url=http://www.bentham-direct.org/pages/content.php?CDT/2005/] , unwanted psychological influences and other adverse effects.
The "N"-methyl-D-aspartate (NMDA) receptor seems to play a major role in neuropathic pain and in the development of opioid tolerance.
Dextromethorphanis an NMDA antagonist at high doses.
Experiments in both animals and humans have established that NMDA antagonists such as
ketamineand dextromethorphancan alleviate neuropathic pain and reverse opioid tolerance.cite journal |author=Nelson KA, Park KM, Robinovitz E, Tsigos C, Max MB |title=High-dose oral dextromethorphan versus placebo in painful diabetic neuropathy and postherpetic neuralgia |journal=Neurology |volume=48 |issue=5 |pages=1212–8 |year=1997 |pmid=9153445 |doi=] Unfortunately, only a few NMDA antagonists are clinically available and their use is limited by unacceptable side effects.
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 systemare sometimes carried out.
There are two dietary supplements that have clinical evidence showing them to be effective treatments of diabetic neuropathy; alpha lipoic acid and benfotiamine.cite journal |author=Head KA |title=Peripheral neuropathy: pathogenic mechanisms and alternative therapies |journal=Altern Med Rev |volume=11 |issue=4 |pages=294–329 |year=2006 |pmid=17176168 |doi= |url=http://www.thorne.com/altmedrev/.fulltext/11/4/294.pdf |format=PDF]
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.cite journal |author=Foster TS |title=Efficacy and safety of alpha-lipoic acid supplementation in the treatment of symptomatic diabetic neuropathy |journal=Diabetes Educ |volume=33 |issue=1 |pages=111–7 |year=2007 |pmid=17272797 |doi=10.1177/0145721706297450 |quote=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.] 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),cite journal |author=Ziegler D, Ametov A, Barinov A, "et al" |title=Oral treatment with alpha-lipoic acid improves symptomatic diabetic polyneuropathy: the SYDNEY 2 trial |journal=Diabetes Care |volume=29 |issue=11 |pages=2365–70 |year=2006 |pmid=17065669 |doi=10.2337/dc06-1216] the metanalysis showed "more conflicting data whether it improves sensory symptoms or just neuropathic deficits alone". There is some limited evidence that ALA is also helpful in some other non-diabetic neuropathies.cite journal |author=Patton LL, Siegel MA, Benoliel R, De Laat A |title=Management of burning mouth syndrome: systematic review and management recommendations |journal=Oral Surg Oral Med Oral Pathol Oral Radiol Endod |volume=103 Suppl |issue= |pages=S39.e1–13 |year=2007 |pmid=17379153 |doi=10.1016/j.tripleo.2006.11.009] Benfotiamineis a lipid soluble form of thiamine that has several placebo controlled double blind trials proving efficacy in treating neuropathy and various other diabetic comorbidities.cite journal |author=Stracke H, Lindemann A, Federlin K |title=A benfotiamine-vitamin B combination in treatment of diabetic polyneuropathy |journal=Exp. Clin. Endocrinol. Diabetes |volume=104 |issue=4 |pages=311–6 |year=1996 |pmid=8886748 |doi=] cite journal |author=Thornalley PJ |title=The potential role of thiamine (vitamin B(1)) in diabetic complications |journal=Curr Diabetes Rev |volume=1 |issue=3 |pages=287–98 |year=2005 |pmid=18220605| doi = 10.2174/157339905774574383 ]
In addition to pharmacological treatment several other modalities are commonly recommended.cite journal |author=Chen H, Lamer TJ, Rho RH, "et al" |title=Contemporary management of neuropathic pain for the primary care physician |journal=Mayo Clin. Proc. |volume=79 |issue=12 |pages=1533–45 |year=2004 |pmid=15595338 |doi=] While lacking adequate double blind trials, these have shown to reduce pain and improve patient quality of life for chronic neuropathic pain:
chiropractic, massage, meditation, cognitive therapy,cite journal |author=Kerns JW, White A, Nashelsky J, Sherman S |title=Does psychiatric treatment help patients with intractable chronic pain? |journal=J Fam Pract |volume=55 |issue=3 |pages=235–6 |year=2006 |pmid=16510058 |doi= |url=http://www.jfponline.com/Pages.asp?AID=3897] 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.
Infrared photo therapy has been used to treat neuropathic symptoms. [cite web |author=Burke T |title=Part 9. How Light (Photo Energy) May Increase Local NO and Vasodilation |work=Nitric Oxide and Its Role in Health and Diabetes |url=http://www.diabetesincontrol.com/burkearchive/nitricoxide9.shtml |publisher=Diabetes In Control |accessdate=2008-03-28] However, recent work has cast doubt on the value of this approach.cite journal |author=Lavery LA, Murdoch DP, Williams J, Lavery DC |title=Does anodyne light therapy improve peripheral neuropathy in diabetes? A double-blind, sham-controlled, randomized trial to evaluate monochromatic infrared photoenergy |journal=Diabetes Care |volume=31 |issue=2 |pages=316–21 |year=2008 |pmid=17977931 |doi=10.2337/dc07-1794]
Neuromodulation is a field of science, medicine and bioengineering that encompasses both implantable and non-implantable technologies (electrical and chemical) for treatment purposes. [Krames ES. Neuromodulatory devices are part of our "Tools of the Trade". Pain Med 2006;7:S3-5.]
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. Lack of pain relief sometimes prompts device removal. [cite journal |author=Turner JA, Loeser JD, Deyo RA, Sanders SB |title=Spinal cord stimulation for patients with failed back surgery syndrome or complex regional pain syndrome: a systematic review of effectiveness and complications |journal=Pain |volume=108 |issue=1-2 |pages=137–47 |year=2004 |pmid=15109517 |doi=10.1016/j.pain.2003.12.016]
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 [cite journal |author=Lynch SS, Cheng CM, Yee JL |title=Intrathecal ziconotide for refractory chronic pain |journal=Ann Pharmacother |volume=40 |issue=7-8 |pages=1293–300 |year=2006 |pmid=16849624 |doi=10.1345/aph.1G584] are infused. Complications such as, serious infection (meningitis), urinary retention, hormonal disturbance and intrathecal granuloma formation have been noted.
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. [cite journal |author=Turner JA, Sears JM, Loeser JD |title=Programmable intrathecal opioid delivery systems for chronic noncancer pain: a systematic review of effectiveness and complications |journal=Clin J Pain |volume=23 |issue=2 |pages=180–95 |year=2007 |pmid=17237668 |doi=10.1097/01.ajp.0000210955.93878.44] 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. [Brown JA, Pilitsis JG. Motor Cortex StimulationPain Medicine 2006; 7:S140. ] [Osenbach, R. Neurostimulation for the Treatment of Intractable Facial PainPain Medicine 2006; 7:S126]
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%). [cite journal |author=Bittar RG, Kar-Purkayastha I, Owen SL, "et al" |title=Deep brain stimulation for pain relief: a meta-analysis |journal=J Clin Neurosci |volume=12 |issue=5 |pages=515–9 |year=2005 |pmid=15993077 |doi=10.1016/j.jocn.2004.10.005] There is a significant complication rate which increase over time. [cite journal |author=Oh MY, Abosch A, Kim SH, Lang AE, Lozano AM |title=Long-term hardware-related complications of deep brain stimulation |journal=Neurosurgery |volume=50 |issue=6 |pages=1268–74; discussion 1274–6 |year=2002 |pmid=12015845| doi = 10.1097/00006123-200206000-00017 ]
Peripheral nervous system
Small fiber peripheral neuropathy
Neuropathy related organizations
* [http://www.canadianneuropathyassociation.org Canadian Neuropathy Association]
* [http://www.neupsig.org/ Special Interest Group on Neuropathic Pain] of the [http://www.iasp-pain.org International Association for the Study of Pain (IASP)]
* [http://www.neuropathy.org/site/PageServer The Neuropathy Association] - United States
* [http://www.paintrials.org BWH Translational Pain Research]
* [http://www.neurocentre.com Neuropathy Trust - United Kingdom]
* [http://www.actionontario.ca Action Ontario is a not-for-profit organization, which advocates on behalf of neuropathic pain suffers]
* [http://www.neurocentre.com/slanss.php S-LANSS Pain Scale Questionnaire for Help in the Diagnosis of Neuropathic Pain]
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neuropathy — n. any disease of the peripheral nerves, usually causing weakness and numbness. In a mononeuropathy a single nerve is affected and the extent of the symptoms depends upon the distribution of that nerve. In a polyneuropathy (see peripheral… … The new mediacal dictionary
neuropathy — A nerve problem that causes pain, numbness, tingling, swelling, or muscle weakness in different parts of the body. It usually begins in the hands or feet and gets worse over time. Neuropathy may be caused by physical injury, infection, toxic… … English dictionary of cancer terms
neuropathy — noun (plural thies) Etymology: International Scientific Vocabulary Date: circa 1857 an abnormal and usually degenerative state of the nervous system or nerves; also a systemic condition that stems from a neuropathy • neuropathic adjective •… … New Collegiate Dictionary
neuropathy — noun any pathology of the peripheral nerves • Hypernyms: ↑pathology • Hyponyms: ↑Charcot Marie Tooth disease, ↑hereditary motor and sensory neuropathy, ↑mononeuropathy, ↑multiple mononeuropathy … Useful english dictionary
neuropathy — neuropathic /noor euh path ik, nyoor /, adj. neuropathically, adv. /noo rop euh thee, nyoo /, n. any diseased condition of the nervous system. [1855 60; NEURO + PATHY] * * * Disorder of the peripheral nervous system. It may be genetic or acquired … Universalium
neuropathy — noun Any disease of the peripheral nervous system … Wiktionary