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{{Peripheral neuropathy}}
{{Peripheral neuropathy}}
{{CMG}}; {{AE}}{{MMJ}}
==Overview==
Pharmacologic medical therapy is recommended among patients with peripheral neuropathy. Peripheral neuropathy, caused by various central and peripheral [[nerve]] disorders, is especially problematic because of its severity, chronicity and resistance to simple [[analgesic]]s. According to the cause of the peripheral neuropathy, treatments vary from the choice drug, the dosage of drug and the time of the treatment. Treatments for peripheral neuropathy are generally palliative. Pharmacologic medical therapies for peripheral neuropathy include: Topical [[lidocaine]], [[Gabapentin]], [[pregabalin]], [[Amitriptyline]], [[Nortriptyline]], [[Imipramine|imipramine,]] mixed [[Serotonin-norepinephrine reuptake inhibitor|serotonin–norepinephrine reuptake inhibitors]], [[Tramadol]], [[Buprenorphine|buprenorphine,]] [[Oxycodone]], [[Morphine]], [[Hydrocodone]] and [[Codeine]].


{{CMG}} {{AE}} {{SME}}
==Medical Therapy==
==Medical Therapy==
 
*Pharmacologic medical therapy is recommended among patients with peripheral neuropathy.<ref name="pmid16880448">{{cite journal| author=Gilron I, Watson CP, Cahill CM, Moulin DE| title=Neuropathic pain: a practical guide for the clinician. | journal=CMAJ | year= 2006 | volume= 175 | issue= 3 | pages= 265-75 | pmid=16880448 | doi=10.1503/cmaj.060146 | pmc=1513412 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16880448  }} </ref>
No medical treatments now exist that can cure inherited peripheral neuropathy. However, there are therapies for many other forms. Any underlying condition is treated first, followed by symptomatic treatment. Peripheral nerves have the ability to regenerate, as long as the nerve cell itself has not been killed. Symptoms often can be controlled, and eliminating the causes of specific forms of neuropathy often can prevent new damage.
*Peripheral neuropathy, caused by various central and peripheral [[nerve]] disorders, is especially problematic because of its severity, chronicity and resistance to simple [[analgesic]]s.<ref name="pmid16880448">{{cite journal| author=Gilron I, Watson CP, Cahill CM, Moulin DE| title=Neuropathic pain: a practical guide for the clinician. | journal=CMAJ | year= 2006 | volume= 175 | issue= 3 | pages= 265-75 | pmid=16880448 | doi=10.1503/cmaj.060146 | pmc=1513412 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16880448  }} </ref>
 
*According to the cause of the peripheral neuropathy, treatments vary from the choice drug, the dosage of drug and the time of the treatment.
In general, adopting healthy habits-such as maintaining optimal weight, avoiding exposure to toxins, following a physician-supervised exercise program, eating a balanced diet, correcting vitamin deficiencies, and limiting or avoiding alcohol consumption-can reduce the physical and emotional effects of peripheral neuropathy. Active and passive forms of exercise can reduce cramps, improve muscle strength, and prevent muscle wasting in paralyzed limbs. Various dietary strategies can improve gastrointestinal symptoms. Timely treatment of injury can help prevent permanent damage. Quitting smoking is particularly important because smoking constricts the blood vessels that supply nutrients to the peripheral nerves and can worsen neuropathic symptoms. Self-care skills such as meticulous foot care and careful wound treatment in people with diabetes and others who have an impaired ability to feel pain can alleviate symptoms and improve quality of life. Such changes often create conditions that encourage nerve regeneration.
*Treatments for peripheral neuropathy are generally palliative.
 
*Pharmacologic medical therapies for peripheral neuropathy include:<ref name="pmid16880448">{{cite journal| author=Gilron I, Watson CP, Cahill CM, Moulin DE| title=Neuropathic pain: a practical guide for the clinician. | journal=CMAJ | year= 2006 | volume= 175 | issue= 3 | pages= 265-75 | pmid=16880448 | doi=10.1503/cmaj.060146 | pmc=1513412 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16880448  }} </ref>
Systemic diseases frequently require more complex treatments. Strict control of blood glucose levels has been shown to reduce neuropathic symptoms and help people with diabetic neuropathy avoid further nerve damage. Inflammatory and autoimmune conditions leading to neuropathy can be controlled in several ways. Immunosuppressive drugs such as prednisone, cyclosporine, or azathioprine may be beneficial. Plasmapheresis-a procedure in which blood is removed, cleansed of immune system cells and antibodies, and then returned to the body-can limit inflammation or suppress immune system activity. High doses of immunoglobulins, proteins that function as antibodies, also can suppress abnormal immune system activity.
**Topical [[lidocaine]]<ref name="pmid22059196">{{cite journal| author=Delorme C, Navez ML, Legout V, Deleens R, Moyse D| title=Treatment of neuropathic pain with 5% lidocaine-medicated plaster: Five years of clinical experience. | journal=Pain Res Manag | year= 2011 | volume= 16 | issue= 4 | pages= 259-63 | pmid=22059196 | doi= | pmc=3202378 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22059196  }} </ref>
 
**[[Gabapentin]]<ref name="pmid29178034">{{cite journal| author=Fornasari D| title=Pharmacotherapy for Neuropathic Pain: A Review. | journal=Pain Ther | year= 2017 | volume= 6 | issue= Suppl 1 | pages= 25-33 | pmid=29178034 | doi=10.1007/s40122-017-0091-4 | pmc=5701897 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29178034  }} </ref>
Neuropathic pain is often difficult to control. Mild pain may sometimes be alleviated by analgesics sold over the counter. Several classes of drugs have recently proved helpful to many patients suffering from more severe forms of chronic neuropathic pain. These include mexiletine, a drug developed to correct irregular heart rhythms (sometimes associated with severe side effects); several antiepileptic drugs, including gabapentin, phenytoin, and carbamazepine; and some classes of antidepressants, including tricyclics such as amitriptyline. Injections of local anesthetics such as lidocaine or topical patches containing lidocaine may relieve more intractable pain. In the most severe cases, doctors can surgically destroy nerves; however, the results are often temporary and the procedure can lead to complications.
**[[Pregabalin]]<ref name="pmid28292992">{{cite journal| author=Nishikawa T, Hasegawa K, Shintani D, Yano Y, Sato S, Yabuno A et al.| title=[Combination Therapy of Pregabalin with Tramadol for Treatment of Peripheral Neuropathy in Patients with Gynecological Cancer Receiving Taxane Containing Chemotherapy]. | journal=Gan To Kagaku Ryoho | year= 2017 | volume= 44 | issue= 3 | pages= 227-231 | pmid=28292992 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28292992  }} </ref>
 
**[[Tricyclic antidepressants]]:<ref name="pmid17314585">{{cite journal| author=Berger A, Dukes E, Edelsberg J, Stacey B, Oster G| title=Use of tricyclic antidepressants in older patients with diabetic peripheral neuropathy. | journal=Clin J Pain | year= 2007 | volume= 23 | issue= 3 | pages= 251-8 | pmid=17314585 | doi=10.1097/AJP.0b013e31802f67dd | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17314585  }} </ref>
Mechanical aids can help reduce pain and lessen the impact of physical disability. Hand or foot braces can compensate for muscle weakness or alleviate nerve compression. Orthopedic shoes can improve gait disturbances and help prevent foot injuries in people with a loss of pain sensation. If breathing becomes severely impaired, mechanical ventilation can provide essential life support.
***[[Amitriptyline]]
 
***[[Nortriptyline]]
===Treatment of Neuropathic Pain===
***[[Imipramine]]
Neuropathic pain can be very difficult to treat. Sometimes strong [[opioid]] analgesics  may provide only partial relief. Opioid analgesics are to be considered only as a tertiary treatment.  Several classes of medications not normally thought of as analgesics are often effective, alone or in combination with opioids and other treatments. These include [[tricyclic antidepressant]]s such as [[amitriptyline]] (Elavil®), [[anticonvulsant]]s such as [[gabapentin]] (Neurontin®) and [[pregabalin]] (Lyrica®).
**Mixed [[Serotonin-norepinephrine reuptake inhibitor|serotonin–norepinephrine reuptake inhibitors]]<ref name="pmid24577146">{{cite journal| author=Aziz MT, Good BL, Lowe DK| title=Serotonin-norepinephrine reuptake inhibitors for the management of chemotherapy-induced peripheral neuropathy. | journal=Ann Pharmacother | year= 2014 | volume= 48 | issue= 5 | pages= 626-32 | pmid=24577146 | doi=10.1177/1060028014525033 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24577146  }} </ref><ref name="pmid20514212">{{cite journal| author=Marks DM, Shah MJ, Patkar AA, Masand PS, Park GY, Pae CU| title=Serotonin-norepinephrine reuptake inhibitors for pain control: premise and promise. | journal=Curr Neuropharmacol | year= 2009 | volume= 7 | issue= 4 | pages= 331-6 | pmid=20514212 | doi=10.2174/157015909790031201 | pmc=2811866 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20514212 }} </ref>
 
**[[Tramadol]]<ref name="pmid28292992">{{cite journal| author=Nishikawa T, Hasegawa K, Shintani D, Yano Y, Sato S, Yabuno A et al.| title=[Combination Therapy of Pregabalin with Tramadol for Treatment of Peripheral Neuropathy in Patients with Gynecological Cancer Receiving Taxane Containing Chemotherapy]. | journal=Gan To Kagaku Ryoho | year= 2017 | volume= 44 | issue= 3 | pages= 227-231 | pmid=28292992 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28292992  }} </ref>
In animal models of neuropathic pain it has been found that compounds which only block serotonin reuptake do not improve neuropathic pain.<!--
**[[Opioids]]:<ref name="pmid20571607">{{cite journal| author=Raffa RB, Pergolizzi JV, Segarnick DJ, Tallarida RJ| title=Oxycodone combinations for pain relief. | journal=Drugs Today (Barc) | year= 2010 | volume= 46 | issue= 6 | pages= 379-98 | pmid=20571607 | doi=10.1358/dot.2010.46.6.1470106 | pmc=4046166 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20571607  }} </ref>
  --><ref>{{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}}</ref><!--
***[[Buprenorphine]]
  --><ref>{{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 |issue=2 |pages=205-18 |year=1990 |pmid=1982347}}</ref><!--
***[[Oxycodone]]
  --><ref>{{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}}</ref><!--
***[[Morphine]]
  --><ref>{{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}}</ref><!--
***[[Hydrocodone]]
  --><ref>{{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}}</ref><!--
***[[Codeine]]
  --><ref>{{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}}</ref><!--
  --><ref>{{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}}</ref><!--
  --><ref>{{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}}</ref>
Similarly, compounds that only block [[norepinephrine]] reuptake also do not improve neuropathic pain. Compounds such as [[duloxetine]], [[venlafaxine]], and[[milnacipran]] that block both [[serotonin]] reuptake and norepinephrine reuptake do improve neuropathic pain.
Antidepressants usually reduce neuropathic pain more quickly and with smaller doses than they relieve depression. Antidepressants therefore seem to work differently
on neuropathic pain than on depression, perhaps by activating descending norepinephrinergic and serotonergic pathways in the spinal cord that block pain signals from ascending to the brain.
 
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. The newer anticonvulsants gabapentin and pregabalin appear to work by blocking calcium channels in damaged peripheral neurons.  Tricyclic antidepressants may also work on sodium channels in peripheral nerves.  The anticonvulsants [[carbamazepine]] (Tegretol®) and [[oxcarbazepine]] (Trileptal®), especially effective
on [[trigeminal neuralgia]], are thought to work principally on [[sodium channels]].
 
In general, the antidepressants seem to be most effective on continuous burning pain, while the anticonvulsants seem to
work best on sudden, lancinating, "shock-like" pains that appear to involve large numbers of peripheral nerves improperly firing together.
 
In some forms of neuropathy, especially post-herpes neuralgia, the topical application of local anesthetics such as [[lidocaine]] can provide relief. A transdermal patch containing 5% [[lidocaine]] is available. [[Ketamine]] in a transdermal gel is also frequently effective when the neuropathy is localized. Neurontin 100mg/g PLO gel is also effective for treating peripheral neuropathy, including [[Carpal Tunnel Syndrome]].  [[Capsaicin]] cream can be beneficial in several neurogenic pain disorders, which causes release of the pain neurotransmitter [[Substance P]], and eventually reduces the availability of Substance P.
 
[[Transcutaneous electrical nerve stimulation]] (TENS) is worth a trial in chronic neurogenic pain. Some pain management specialists will try acupuncture, with variable results. TENS, with certain electrical waveforms, appears to have an acupuncture-like function.
 
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. Reducing the sympathetic nerve activity in the painful region with local nerve blocks or systemic medications such as the [[alpha-blocker]] [[clonidine]] may provide relief. Other drugs, known for their ability to desensitize cardiac tissue, include[[beta-blockers]] such as [[propanolol]] and [[calcium channel blockers]] such as [[verapamil]].
 
The [[NMDA receptor]] seems to play a major role in neuropathic pain and in the development of opioid tolerance, and many experiments in both animals and humans have established that NMDA [[Receptor antagonist|antagonists]] such as [[ketamine]] and [[dextromethorphan]] can alleviate neuropathic pain and reverse opioid tolerance. Unfortunately, only a few NMDA antagonists are clinically available and their use is usually associated with unacceptable side effects.
 
Several opioids, particularly [[methadone]], have NMDA antagonist activity in addition to their μ-opioid agonist properties that seems to make them effective against neuropathic pain, although this is still the subject of intensive research and clinical study. Methadone has this property because it is a [[racemic]] mixture; one stereo-isomer is a μ-opioid agonist; the other is a NMDA antagonist.
 
A recent study showed smoking [[marijuana]] is beneficial in treating HIV-associated periphial <!--sp?
  -->neuropathy.<ref>{{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}}</ref>
 
In addition to pharmacological treatment there are several other modalities that help some cases. While lacking double blind trials, these have shown to reduce pain and improve patient quality of life particularly for chronic neuropathic pain: Interferential Stimulation; [[Acupuncture]]; [[Meditation]]; [[Cognitive Therapy]]; and prescribed exercise.
 
In more recent years, infrared photo therapy has been used to treat neuropathic symptoms. Photo therapy devices emit near [[infrared light]] typically at a wavelength of 890nm. This wavelength is believed to stimulate the release of [[nitric oxide]], an [[endothelium-derived relaxing factor]] into the bloodstream, thus vasodilating the capilaries and venuoles in the microcirculatory system. This increase in circulation has been shown effective in various clinical studies, to decrease pain and improve sensation in [[diabetes|diabetic]] and non-diabetic patients. Note that the U.S. [[FDA]] has not approved any infrared photo therapy devices to treat neuropathy.<ref>http://www.healthlight.stirsite.com/page/page/2909659.htm</ref>
 
===Alternative Medicine Treatments==
 
There are 2 dietary supplements that have clinical evidence showing them to be effective treatments of diabetic neuropathy; alpha lipoic acid and benfotiamine. In several studies using a variety of dosages and routes of administration, [[alpha lipoic acid]] was found to reduce the various symptoms of peripheral diabetic neuropathy. A recent review of the published data determined “ALA should be considered as a treatment option for patients with peripheral diabetic neuropathy.” Also a recent study using orally administered alpha lipoic acid found that 600 mg once a day caused a marked reduction in the symptoms of diabetic neuropathy including stabbing pain, burning pain, paresthesia, and asleep numbness of the feet.
[[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. 400 mg a day was the most commonly studied dose.
 
==References==
==References==
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Latest revision as of 16:09, 5 September 2018

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mohamadmostafa Jahansouz M.D.[2]

Overview

Pharmacologic medical therapy is recommended among patients with peripheral neuropathy. Peripheral neuropathy, caused by various central and peripheral nerve disorders, is especially problematic because of its severity, chronicity and resistance to simple analgesics. According to the cause of the peripheral neuropathy, treatments vary from the choice drug, the dosage of drug and the time of the treatment. Treatments for peripheral neuropathy are generally palliative. Pharmacologic medical therapies for peripheral neuropathy include: Topical lidocaine, Gabapentin, pregabalin, Amitriptyline, Nortriptyline, imipramine, mixed serotonin–norepinephrine reuptake inhibitors, Tramadol, buprenorphine, Oxycodone, Morphine, Hydrocodone and Codeine.

Medical Therapy

References

  1. ↑ 1.0 1.1 1.2 Gilron I, Watson CP, Cahill CM, Moulin DE (2006). "Neuropathic pain: a practical guide for the clinician". CMAJ. 175 (3): 265–75. doi:10.1503/cmaj.060146. PMC 1513412. PMID 16880448.
  2. ↑ Delorme C, Navez ML, Legout V, Deleens R, Moyse D (2011). "Treatment of neuropathic pain with 5% lidocaine-medicated plaster: Five years of clinical experience". Pain Res Manag. 16 (4): 259–63. PMC 3202378. PMID 22059196.
  3. ↑ Fornasari D (2017). "Pharmacotherapy for Neuropathic Pain: A Review". Pain Ther. 6 (Suppl 1): 25–33. doi:10.1007/s40122-017-0091-4. PMC 5701897. PMID 29178034.
  4. ↑ 4.0 4.1 Nishikawa T, Hasegawa K, Shintani D, Yano Y, Sato S, Yabuno A; et al. (2017). "[Combination Therapy of Pregabalin with Tramadol for Treatment of Peripheral Neuropathy in Patients with Gynecological Cancer Receiving Taxane Containing Chemotherapy]". Gan To Kagaku Ryoho. 44 (3): 227–231. PMID 28292992.
  5. ↑ Berger A, Dukes E, Edelsberg J, Stacey B, Oster G (2007). "Use of tricyclic antidepressants in older patients with diabetic peripheral neuropathy". Clin J Pain. 23 (3): 251–8. doi:10.1097/AJP.0b013e31802f67dd. PMID 17314585.
  6. ↑ Aziz MT, Good BL, Lowe DK (2014). "Serotonin-norepinephrine reuptake inhibitors for the management of chemotherapy-induced peripheral neuropathy". Ann Pharmacother. 48 (5): 626–32. doi:10.1177/1060028014525033. PMID 24577146.
  7. ↑ Marks DM, Shah MJ, Patkar AA, Masand PS, Park GY, Pae CU (2009). "Serotonin-norepinephrine reuptake inhibitors for pain control: premise and promise". Curr Neuropharmacol. 7 (4): 331–6. doi:10.2174/157015909790031201. PMC 2811866. PMID 20514212.
  8. ↑ Raffa RB, Pergolizzi JV, Segarnick DJ, Tallarida RJ (2010). "Oxycodone combinations for pain relief". Drugs Today (Barc). 46 (6): 379–98. doi:10.1358/dot.2010.46.6.1470106. PMC 4046166. PMID 20571607.

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