Editing Peripheral neuropathy (section)

==Treatment==
The treatment of peripheral neuropathy varies based on its cause, and treating the underlying condition can help neuropathy treatment. When peripheral neuropathy results from [[diabetes mellitus]] or [[prediabetes]], blood sugar management is key to treatment. In prediabetes, strict blood sugar control can significantly alter the course of neuropathy.<ref name="CioroiuBrannagan2014">{{cite journal | last1=Cioroiu |first1=Comana M. |last2=Brannagan |first2=Thomas H.| title=Peripheral Neuropathy | journal = Current Geriatrics Reports | volume = 3 | issue = 2 | year = 2014 | pages = 83–90 | doi = 10.1007/s13670-014-0079-4 |s2cid=195246984 }}</ref> In peripheral neuropathy that stems from immune-mediated diseases, the underlying condition is treated with [[intravenous immunoglobulin]] or steroids. When peripheral neuropathy results from [[vitamin deficiencies]] or other disorders, those are treated as well.<ref name="CioroiuBrannagan2014"/>

===Medications===
A range of medications that act on the central nervous system have been used to treat [[neuropathic pain]]. Commonly used medications include [[tricyclic antidepressant]]s (such as [[nortriptyline]],<ref name=":0">{{cite journal | vauthors = Derry S, Wiffen PJ, Aldington D, Moore RA | title = Nortriptyline for neuropathic pain in adults | journal = The Cochrane Database of Systematic Reviews | volume = 1 | pages = CD011209 | date = January 2015 | issue = 5 | pmid = 25569864 | pmc = 6485407 | doi = 10.1002/14651858.CD011209.pub2 }}</ref> [[amitriptyline]].<ref name="ReferenceB">{{cite journal | vauthors = Moore RA, Derry S, Aldington D, Cole P, Wiffen PJ | title = Amitriptyline for neuropathic pain in adults | journal = The Cochrane Database of Systematic Reviews | volume = 2015 | issue = 7 | pages = CD008242 | date = July 2015 | pmid = 26146793 | pmc = 6447238 | doi = 10.1002/14651858.CD008242.pub3 }}</ref> [[Imipramine|imapramine]],<ref>{{cite journal | vauthors = Hearn L, Derry S, Phillips T, Moore RA, Wiffen PJ | title = Imipramine for neuropathic pain in adults | journal = The Cochrane Database of Systematic Reviews | volume = 2014 | issue = 5 | pages = CD010769 | date = May 2014 | pmid = 24838845 | pmc = 6485593 | doi = 10.1002/14651858.CD010769.pub2 }}</ref> and [[desipramine]],<ref name=":1" />) [[serotonin-norepinephrine reuptake inhibitor]] (SNRI) medications ([[duloxetine]],<ref>{{cite journal | vauthors = Lunn MP, Hughes RA, Wiffen PJ | title = Duloxetine for treating painful neuropathy, chronic pain or fibromyalgia | journal = The Cochrane Database of Systematic Reviews | issue = 1 | pages = CD007115 | date = January 2014 | volume = 2015 | pmid = 24385423 | doi = 10.1002/14651858.cd007115.pub3 | pmc = 10711341 }}</ref> [[venlafaxine]],<ref>{{cite journal | vauthors = Gallagher HC, Gallagher RM, Butler M, Buggy DJ, Henman MC | title = Venlafaxine for neuropathic pain in adults | journal = The Cochrane Database of Systematic Reviews | issue = 8 | pages = CD011091 | date = August 2015 | volume = 2017 | pmid = 26298465 | pmc = 6481532 | doi = 10.1002/14651858.CD011091.pub2 }}</ref> and [[milnacipran]]<ref>{{cite journal | vauthors = Derry S, Phillips T, Moore RA, Wiffen PJ | title = Milnacipran for neuropathic pain in adults | journal = The Cochrane Database of Systematic Reviews | issue = 7 | pages = CD011789 | date = July 2015 | volume = 2019 | pmid = 26148202 | pmc = 6485877 | doi = 10.1002/14651858.CD011789 }}</ref>) and [[Anticonvulsant|antiepileptic medications]] ([[gabapentin]],<ref name="ReferenceC">{{cite journal | vauthors = Wiffen PJ, Derry S, Bell RF, Rice AS, Tölle TR, Phillips T, Moore RA | title = Gabapentin for chronic neuropathic pain in adults | journal = The Cochrane Database of Systematic Reviews | volume = 6 | pages = CD007938 | date = June 2017 | issue = 2 | pmid = 28597471 | pmc = 6452908 | doi = 10.1002/14651858.CD007938.pub4 }}</ref> [[pregabalin]],<ref name="ReferenceD">{{cite journal | vauthors = Derry S, Bell RF, Straube S, Wiffen PJ, Aldington D, Moore RA | title = Pregabalin for neuropathic pain in adults | journal = The Cochrane Database of Systematic Reviews | volume = 1 | pages = CD007076 | date = January 2019 | issue = 1 | pmid = 30673120 | pmc = 6353204 | doi = 10.1002/14651858.CD007076.pub3 }}</ref> [[oxcarbazepine]]<ref name="Oxcarbazepine for neuropathic pain">{{cite journal | vauthors = Zhou M, Chen N, He L, Yang M, Zhu C, Wu F | title = Oxcarbazepine for neuropathic pain | journal = The Cochrane Database of Systematic Reviews | volume = 2017 | pages = CD007963 | date = December 2017 | issue = 12 | pmid = 29199767 | pmc = 6486101 | doi = 10.1002/14651858.CD007963.pub3 }}</ref> [[zonisamide]]<ref name="ReferenceE">{{cite journal | vauthors = Moore RA, Wiffen PJ, Derry S, Lunn MP | title = Zonisamide for neuropathic pain in adults | journal = The Cochrane Database of Systematic Reviews | volume = 1 | pages = CD011241 | date = January 2015 | issue = 1 | pmid = 25879104 | pmc = 6485502 | doi = 10.1002/14651858.CD011241.pub2 }}</ref> [[levetiracetam]],<ref>{{cite journal | vauthors = Wiffen PJ, Derry S, Moore RA, Lunn MP | editor1-first = Sheena | editor1-last = Derry | title = Levetiracetam for neuropathic pain in adults | journal = The Cochrane Database of Systematic Reviews | issue = 7 | pages = CD010943 | date = July 2014 | volume = 2014 | pmid = 25000215 | pmc = 6485608 | doi = 10.1002/14651858.cd010943.pub2 }}</ref> [[lamotrigine]],<ref>{{cite journal | vauthors = Wiffen PJ, Derry S, Moore RA | title = Lamotrigine for chronic neuropathic pain and fibromyalgia in adults | journal = The Cochrane Database of Systematic Reviews | issue = 12 | pages = CD006044 | date = December 2013 | volume = 2019 | pmid = 24297457 | pmc = 6485508 | doi = 10.1002/14651858.CD006044.pub4 | editor-last = Cochrane Pain, Palliative and Supportive Care Group }}</ref> [[topiramate]],<ref name="ReferenceF">{{cite journal | vauthors = Wiffen PJ, Derry S, Lunn MP, Moore RA | editor1-first = Sheena | editor1-last = Derry | title = Topiramate for neuropathic pain and fibromyalgia in adults | journal = The Cochrane Database of Systematic Reviews | issue = 8 | pages = CD008314 | date = August 2013 | volume = 2013 | pmid = 23996081 | doi = 10.1002/14651858.CD008314.pub3 | pmc = 8406931 }}</ref> [[clonazepam]],<ref>{{cite journal | vauthors = Corrigan R, Derry S, Wiffen PJ, Moore RA | title = Clonazepam for neuropathic pain and fibromyalgia in adults | journal = The Cochrane Database of Systematic Reviews | issue = 5 | pages = CD009486 | date = May 2012 | volume = 2019 | pmid = 22592742 | pmc = 6485609 | doi = 10.1002/14651858.cd009486.pub2 }}</ref> [[phenytoin]],<ref>{{cite journal | vauthors = Birse F, Derry S, Moore RA | title = Phenytoin for neuropathic pain and fibromyalgia in adults | journal = The Cochrane Database of Systematic Reviews | issue = 5 | pages = CD009485 | date = May 2012 | volume = 2019 | pmid = 22592741 | pmc = 6481697 | doi = 10.1002/14651858.cd009485.pub2 }}</ref> [[lacosamide]],<ref>{{cite journal | vauthors = Hearn L, Derry S, Moore RA | title = Lacosamide for neuropathic pain and fibromyalgia in adults | journal = The Cochrane Database of Systematic Reviews | issue = 2 | pages = CD009318 | date = February 2012 | volume = 2016 | pmid = 22336864 | doi = 10.1002/14651858.cd009318.pub2 | pmc = 8406928 }}</ref> [[sodium valproate]]<ref>{{cite journal | vauthors = Gill D, Derry S, Wiffen PJ, Moore RA | title = Valproic acid and sodium valproate for neuropathic pain and fibromyalgia in adults | journal = The Cochrane Database of Systematic Reviews | issue = 10 | pages = CD009183 | date = October 2011 | volume = 2011 | pmid = 21975791 | pmc = 6540387 | doi = 10.1002/14651858.cd009183.pub2 }}</ref> and [[carbamazepine]]<ref>{{cite journal | vauthors = Wiffen PJ, Derry S, Moore RA, Kalso EA | title = Carbamazepine for chronic neuropathic pain and fibromyalgia in adults | journal = The Cochrane Database of Systematic Reviews | issue = 4 | pages = CD005451 | date = April 2014 | volume = 2019 | pmid = 24719027 | pmc = 6491112 | doi = 10.1002/14651858.CD005451.pub3 | editor-last = Cochrane Pain, Palliative and Supportive Care Group }}</ref>). [[Opioid]] and [[opiate]] medications (such as [[buprenorphine]],<ref name=":6">{{cite journal | vauthors = Wiffen PJ, Derry S, Moore RA, Stannard C, Aldington D, Cole P, Knaggs R | title = Buprenorphine for neuropathic pain in adults | journal = The Cochrane Database of Systematic Reviews | issue = 9 | pages = CD011603 | date = September 2015 | volume = 2019 | pmid = 26421677 | pmc = 6481375 | doi = 10.1002/14651858.CD011603.pub2 }}</ref> [[morphine]],<ref name=":7" /> [[methadone]],<ref name=":8">{{cite journal | vauthors = McNicol ED, Ferguson MC, Schumann R | title = Methadone for neuropathic pain in adults | journal = The Cochrane Database of Systematic Reviews | volume = 5 | pages = CD012499 | date = May 2017 | issue = 5 | pmid = 28514508 | pmc = 6353163 | doi = 10.1002/14651858.CD012499.pub2 | editor-last = Cochrane Pain, Palliative and Supportive Care Group }}</ref> [[fentanyl]],<ref name=":9">{{cite journal | vauthors = Derry S, Stannard C, Cole P, Wiffen PJ, Knaggs R, Aldington D, Moore RA | title = Fentanyl for neuropathic pain in adults | journal = The Cochrane Database of Systematic Reviews | volume = 10 | pages = CD011605 | date = October 2016 | issue = 5 | pmid = 27727431 | pmc = 6457928 | doi = 10.1002/14651858.CD011605.pub2 }}</ref> [[hydromorphone]],<ref name=":10">{{cite journal | vauthors = Stannard C, Gaskell H, Derry S, Aldington D, Cole P, Cooper TE, Knaggs R, Wiffen PJ, Moore RA | title = Hydromorphone for neuropathic pain in adults | journal = The Cochrane Database of Systematic Reviews | issue = 5 | pages = CD011604 | date = May 2016 | volume = 2016 | pmid = 27216018 | pmc = 6491092 | doi = 10.1002/14651858.CD011604.pub2 }}</ref> [[tramadol]]<ref name=":11" /> and [[oxycodone]]<ref name=":12">{{cite journal | vauthors = Gaskell H, Derry S, Stannard C, Moore RA | title = Oxycodone for neuropathic pain in adults | journal = The Cochrane Database of Systematic Reviews | volume = 2016 | pages = CD010692 | date = July 2016 | issue = 7 | pmid = 27465317 | pmc = 6457997 | doi = 10.1002/14651858.CD010692.pub3 | editor-last = Cochrane Pain, Palliative and Supportive Care Group }}</ref>) are also often used to treat neuropathic pain.

As is revealed in many of the Cochrane systematic reviews listed below, studies of these medications for the treatment of neuropathic pain are often methodologically flawed and the evidence is potentially subject to major bias. In general, the evidence does not support the usage of antiepileptic and antidepressant medications for the treatment of neuropathic pain. Better-designed clinical trials and further review from non-biased third parties are necessary to gauge just how useful for patients these medications truly are. Reviews of these systematic reviews are also necessary to assess their failings.

It is also often the case that the aforementioned medications are prescribed for neuropathic pain conditions for which they had not been explicitly tested for which controlled research is severely lacking; or even for which evidence suggests that these medications are not effective.<ref>{{cite journal | vauthors = Mafi JN, McCarthy EP, Davis RB, Landon BE | title = Worsening trends in the management and treatment of back pain | journal = JAMA Internal Medicine | volume = 173 | issue = 17 | pages = 1573–81 | date = September 2013 | pmid = 23896698 | pmc = 4381435 | doi = 10.1001/jamainternmed.2013.8992 }}</ref><ref>{{cite journal | vauthors = Pinto RZ, Maher CG, Ferreira ML, Ferreira PH, Hancock M, Oliveira VC, McLachlan AJ, Koes B | title = Drugs for relief of pain in patients with sciatica: systematic review and meta-analysis | journal = BMJ | volume = 344 | pages = e497 | date = February 2012 | pmid = 22331277 | pmc = 3278391 | doi = 10.1136/bmj.e497 }}</ref><ref>{{cite journal | vauthors = Pinto RZ, Verwoerd AJ, Koes BW | title = Which pain medications are effective for sciatica (radicular leg pain)? | journal = BMJ | volume = 359 | pages = j4248 | date = October 2017 | pmid = 29025735 | doi = 10.1136/bmj.j4248 | s2cid = 11229746 }}</ref> The NHS for example explicitly states that amitriptyline and gabapentin can be used for treating the pain of sciatica.<ref>{{Cite web|url=https://www.nhs.uk/live-well/healthy-body/which-painkiller-to-use/|title=Which painkiller?|date=2018-04-26|website=nhs.uk|language=en|access-date=2019-05-20}}</ref> This is despite both the lack of high-quality evidence that demonstrates the efficacy of these medications for that symptom,<ref name="ReferenceB"/><ref name="ReferenceC"/> and also the prominence of generally moderate to high-quality evidence that reveals that antiepileptics in specific, including gabapentin, demonstrate no efficacy in treating it.<ref>{{cite journal | vauthors = Enke O, New HA, New CH, Mathieson S, McLachlan AJ, Latimer J, Maher CG, Lin CC | title = Anticonvulsants in the treatment of low back pain and lumbar radicular pain: a systematic review and meta-analysis | journal = CMAJ | volume = 190 | issue = 26 | pages = E786–E793 | date = July 2018 | pmid = 29970367 | pmc = 6028270 | doi = 10.1503/cmaj.171333  }}</ref>

==== Antidepressants ====
In general, according to Cochrane's systematic reviews, antidepressants have shown to either be ineffective for the treatment of neuropathic pain or the evidence available is inconclusive.<ref name=":0" /><ref name=":1">{{cite journal|vauthors=Hearn L, Moore RA, Derry S, Wiffen PJ, Phillips T|editor1-first=Leslie|editor1-last=Hearn|date=September 2014|title=Desipramine for neuropathic pain in adults|journal=The Cochrane Database of Systematic Reviews|volume=2014 |issue=9|pages=CD011003|doi=10.1002/14651858.CD011003.pub2|pmid=25246131|pmc=6804291}}</ref><ref name=":2">{{cite journal|vauthors=Gallagher HC, Gallagher RM, Butler M, Buggy DJ, Henman MC|date=August 2015|title=Venlafaxine for neuropathic pain in adults|journal=The Cochrane Database of Systematic Reviews|volume=2017|issue=8|pages=CD011091|doi=10.1002/14651858.CD011091.pub2|pmc=6481532|pmid=26298465}}</ref><ref name=":3">{{cite journal|vauthors=Derry S, Phillips T, Moore RA, Wiffen PJ|date=July 2015|title=Milnacipran for neuropathic pain in adults|journal=The Cochrane Database of Systematic Reviews|volume=2019 |issue=7|pages=CD011789|doi=10.1002/14651858.CD011789|pmc=6485877|pmid=26148202}}</ref> Evidence also tends to be tainted by bias or issues with the methodology.<ref name=":4">{{cite journal|vauthors=Moore RA, Derry S, Aldington D, Cole P, Wiffen PJ|date=July 2015|editor-last=Cochrane Pain, Palliative and Supportive Care Group|title=Amitriptyline for neuropathic pain in adults|journal=The Cochrane Database of Systematic Reviews|volume=2015 |issue=7|pages=CD008242|doi=10.1002/14651858.CD008242.pub3|pmc=6447238|pmid=26146793}}</ref><ref name=":5">{{cite journal|vauthors=Hearn L, Derry S, Phillips T, Moore RA, Wiffen PJ|date=May 2014|title=Imipramine for neuropathic pain in adults|journal=The Cochrane Database of Systematic Reviews|volume=2019 |issue=5|pages=CD010769|doi=10.1002/14651858.CD010769.pub2|pmc=6485593|pmid=24838845}}</ref>

Cochrane systematically reviewed the evidence for the antidepressants nortriptyline, desipramine, venlafaxine, and milnacipran and in all these cases found scant evidence to support their use for the treatment of neuropathic pain. All reviews were done between 2014 and 2015.<ref name=":0" /><ref name=":1" /><ref name=":2" /><ref name=":3" />

A 2015 Cochrane systematic review of amitriptyline found no evidence supporting [[amitriptyline]] that did not possess inherent bias. The authors believe amitriptyline may have an effect in some patients but that the effect is overestimated.<ref name=":4" /> A 2014 Cochrane systematic review of imipramine notes that the evidence suggesting benefit were "methodologically flawed and potentially subject to major bias."<ref name=":5" />

A 2017 Cochrane systematic review assessed the benefit of antidepressant medications for several types of chronic non-cancer pains (including neuropathic pain) in children and adolescents and the authors found the evidence inconclusive.<ref>{{cite journal | vauthors = Cooper TE, Heathcote LC, Clinch J, Gold JI, Howard R, Lord SM, Schechter N, Wood C, Wiffen PJ | title = Antidepressants for chronic non-cancer pain in children and adolescents | journal = The Cochrane Database of Systematic Reviews | volume = 8 | pages = CD012535 | date = August 2017 | issue = 8 | pmid = 28779487 | pmc = 6424378 | doi = 10.1002/14651858.CD012535.pub2 }}</ref>

==== Antiepileptics ====
A 2017 Cochrane systematic review found that daily dosages between 1800–3600&nbsp;mg of gabapentin could provide good pain relief for pain associated with diabetic neuropathy only. This relief occurred for roughly 30–40% of treated patients, while placebo had a 10–20% response. Three of the seven authors of the review had conflicts of interest declared.<ref name="ReferenceC"/> In a 2019 Cochrane review of pregabalin the authors conclude that there is some evidence of efficacy in the treatment of pain deriving from post-herpetic neuralgia, diabetic neuropathy, and post-traumatic neuropathic pain only. They also warned that many patients treated will have no benefit. Two of the five authors declared receiving payments from pharmaceutical companies.<ref name="ReferenceD"/>

A 2017 Cochrane systematic review found that oxcarbazepine had little evidence to support its use for treating diabetic neuropathy, radicular pain, and other neuropathies. The authors also call for better studies.<ref name="Oxcarbazepine for neuropathic pain"/> In a 2015 Cochrane systematic review the authors found a lack of evidence showing any effectiveness of zonisamide for treating pain deriving from any peripheral neuropathy.<ref name="ReferenceE"/> A 2014 Cochrane review found that studies of levetiracetam showed no indication of its effectiveness at treating pain from any neuropathy. The authors also found that the evidence was possibly biased and that some patients experienced adverse events.<ref>{{cite journal | vauthors = Wiffen PJ, Derry S, Moore RA, Lunn MP | editor1-first = Sheena | editor1-last = Derry | title = Levetiracetam for neuropathic pain in adults | journal = The Cochrane Database of Systematic Reviews | issue = 7 | pages = CD010943 | date = July 2014 | volume = 2014 | pmid = 25000215 | pmc = 6485608 | doi = 10.1002/14651858.CD010943.pub2 }}</ref>

A 2013 Cochrane systematic review concluded that there was high-quality evidence to suggest that lamotrigine is not effective for treating neuropathic pain, even at high dosages 200–400&nbsp;mg.<ref>{{cite journal | vauthors = Wiffen PJ, Derry S, Moore RA | title = Lamotrigine for chronic neuropathic pain and fibromyalgia in adults | journal = The Cochrane Database of Systematic Reviews | issue = 12 | pages = CD006044 | date = December 2013 | volume = 2019 | pmid = 24297457 | pmc = 6485508 | doi = 10.1002/14651858.CD006044.pub4 }}</ref> A 2013 Cochrane systematic review of topiramate found that the included data had a strong likelihood of major bias; despite this, it found no effectiveness for the drug in treating the pain associated with diabetic neuropathy. It had not been tested for any other type of neuropathy.<ref name="ReferenceF"/> Cochrane reviews from 2012 of clonazepam and phenytoin uncovered no evidence of sufficient quality to support their use in chronic neuropathic pain."<ref>{{cite journal | vauthors = Corrigan R, Derry S, Wiffen PJ, Moore RA | title = Clonazepam for neuropathic pain and fibromyalgia in adults | journal = The Cochrane Database of Systematic Reviews | issue = 5 | pages = CD009486 | date = May 2012 | volume = 2019 | pmid = 22592742 | pmc = 6485609 | doi = 10.1002/14651858.CD009486.pub2 }}</ref><ref>{{cite journal | vauthors = Birse F, Derry S, Moore RA | title = Phenytoin for neuropathic pain and fibromyalgia in adults | journal = The Cochrane Database of Systematic Reviews | issue = 5 | pages = CD009485 | date = May 2012 | volume = 2019 | pmid = 22592741 | pmc = 6481697 | doi = 10.1002/14651858.CD009485.pub2 }}</ref>

A 2012 Cochrane systematic review of lacosamide found it very likely that the drug is ineffective for treating neuropathic pain. The authors caution against positive interpretations of the evidence.<ref>{{cite journal | vauthors = Hearn L, Derry S, Moore RA | title = Lacosamide for neuropathic pain and fibromyalgia in adults | journal = The Cochrane Database of Systematic Reviews | issue = 2 | pages = CD009318 | date = February 2012 | volume = 2016 | pmid = 22336864 | doi = 10.1002/14651858.CD009318.pub2 | pmc = 8406928 }}</ref> For sodium valproate the authors of a 2011 Cochrane review found that "three studies no more than hint that sodium valproate may reduce pain in diabetic neuropathy". They discuss how there is a probable overestimate of the effect due to the inherent problems with the data and conclude that the evidence does not support its usage.<ref>{{cite journal | vauthors = Gill D, Derry S, Wiffen PJ, Moore RA | title = Valproic acid and sodium valproate for neuropathic pain and fibromyalgia in adults | journal = The Cochrane Database of Systematic Reviews | issue = 10 | pages = CD009183 | date = October 2011 | volume = 2011 | pmid = 21975791 | doi = 10.1002/14651858.CD009183.pub2 | pmc = 6540387 }}</ref> In a 2014 systematic review of carbamazepine the authors believe the drug benefits some people. No trials were considered greater than level III evidence; none lasted longer than 4 weeks and had poor reporting quality.<ref>{{cite journal | vauthors = Wiffen PJ, Derry S, Moore RA, Kalso EA | title = Carbamazepine for chronic neuropathic pain and fibromyalgia in adults | journal = The Cochrane Database of Systematic Reviews | issue = 4 | pages = CD005451 | date = April 2014 | volume = 2019 | pmid = 24719027 | pmc = 6491112 | doi = 10.1002/14651858.cd005451.pub3 }}</ref>

A 2017 Cochrane systematic review aiming to assess the benefit of antiepileptic medications for several types of chronic non-cancer pains (including neuropathic pain) in children and adolescents found the evidence inconclusive. Two of the ten authors of this study declared receiving payments from pharmaceutical companies.<ref>{{cite journal | vauthors = Cooper TE, Wiffen PJ, Heathcote LC, Clinch J, Howard R, Krane E, Lord SM, Sethna N, Schechter N, Wood C | title = Antiepileptic drugs for chronic non-cancer pain in children and adolescents | journal = The Cochrane Database of Systematic Reviews | volume = 8 | pages = CD012536 | date = August 2017 | issue = 8 | pmid = 28779491 | pmc = 6424379 | doi = 10.1002/14651858.CD012536.pub2 }}</ref>

==== Opioids ====
A Cochrane review of buprenorphine, fentanyl, hydromorphone, and morphine, all dated between 2015 and 2017, and all for the treatment of neuropathic pain, found that there was insufficient evidence to comment on their efficacy. Conflicts of interest were declared by the authors in this review.<ref name=":6" /><ref name=":7">{{cite journal | vauthors = Cooper TE, Chen J, Wiffen PJ, Derry S, Carr DB, Aldington D, Cole P, Moore RA | title = Morphine for chronic neuropathic pain in adults | journal = The Cochrane Database of Systematic Reviews | volume = 2019 | pages = CD011669 | date = May 2017 | issue = 5 | pmid = 28530786 | pmc = 6481499 | doi = 10.1002/14651858.CD011669.pub2 }}</ref><ref name=":9" /><ref name=":10" /> A 2017 Cochrane review of methadone found very low-quality evidence, three studies of limited quality, of its efficacy and safety. They could not formulate any conclusions about its relative efficacy and safety compared to a placebo.<ref name=":8" />

For tramadol, Cochrane found that there was only modest information about the benefits of its usage for neuropathic pain. Studies were small, had potential risks of bias and apparent benefits increased with risk of bias. Overall the evidence was of low or very low quality and the authors state that it "does not provide a reliable indication of the likely effect".<ref name=":11">{{cite journal | vauthors = Duehmke RM, Derry S, Wiffen PJ, Bell RF, Aldington D, Moore RA | title = Tramadol for neuropathic pain in adults | journal = The Cochrane Database of Systematic Reviews | volume = 2017 | pages = CD003726 | date = June 2017 | issue = 6 | pmid = 28616956 | pmc = 6481580 | doi = 10.1002/14651858.CD003726.pub4 }}</ref> For oxycodone the authors found very low-quality evidence showing its usefulness in treating diabetic neuropathy and postherpetic neuralgia only. One of the four authors declared receiving payments from pharmaceutical companies.<ref name=":12" />

More generally, a large-scale 2013 review found opioids to be more effective for intermediate-term use than short-term use, but couldn't properly assess effectiveness for chronic use because of insufficient data. Most recent guidelines on the pharmacotherapy of neuropathic pain however are in agreement with the results of this review and recommend the use of opioids.<ref>{{cite journal | vauthors = McNicol ED, Midbari A, Eisenberg E | title = Opioids for neuropathic pain | journal = The Cochrane Database of Systematic Reviews | issue = 8 | pages = CD006146 | date = August 2013 | volume = 2019 | pmid = 23986501 | pmc = 6353125 | doi = 10.1002/14651858.CD006146.pub2 }}</ref> A 2017 Cochrane review examining mainly propoxyphene therapy as a treatment for many non-cancer pain syndromes (including neuropathic pain) concluded, "There was no evidence from randomised controlled trials to support or refute the use of opioids to treat chronic non-cancer pain in children and adolescents."<ref>{{cite journal | vauthors = Cooper TE, Fisher E, Gray AL, Krane E, Sethna N, van Tilburg MA, Zernikow B, Wiffen PJ | title = Opioids for chronic non-cancer pain in children and adolescents | journal = The Cochrane Database of Systematic Reviews | volume = 7 | pages = CD012538 | date = July 2017 | issue = 7 | pmid = 28745394 | pmc = 6477875 | doi = 10.1002/14651858.CD012538.pub2 }}</ref>

==== Others ====
A 2016 Cochrane review of [[paracetamol]] for the treatment of neuropathic pain concluded that its benefit alone or in combination with codeine or dihydrocodeine is unknown.<ref>{{cite journal | vauthors = Wiffen PJ, Knaggs R, Derry S, Cole P, Phillips T, Moore RA | title = Paracetamol (acetaminophen) with or without codeine or dihydrocodeine for neuropathic pain in adults | journal = The Cochrane Database of Systematic Reviews | volume = 12 | pages = CD012227 | date = December 2016 | issue = 5 | pmid = 28027389 | pmc = 6463878 | doi = 10.1002/14651858.CD012227.pub2 }}</ref>

Few studies have examined whether [[nonsteroidal anti-inflammatory drug]]s are effective in treating peripheral neuropathy.<ref name="Moore2015">{{cite journal | vauthors = Moore RA, Chi CC, Wiffen PJ, Derry S, Rice AS | title = Oral nonsteroidal anti-inflammatory drugs for neuropathic pain | journal = The Cochrane Database of Systematic Reviews | volume = 10 | issue = 10 | pages = CD010902 | date = October 2015 | pmid = 26436601 | pmc = 6481590 | doi = 10.1002/14651858.CD010902.pub2 }}</ref>

There is some evidence that symptomatic relief from the pain of peripheral neuropathy may be obtained by the application of topical [[capsaicin]]. Capsaicin is the factor that causes heat in chili peppers. However, the evidence suggesting that capsaicin applied to the skin reduces pain for peripheral neuropathy is of moderate to low quality and should be interpreted carefully before this treatment is used.<ref>{{cite journal | vauthors = Derry S, Rice AS, Cole P, Tan T, Moore RA | title = Topical capsaicin (high concentration) for chronic neuropathic pain in adults | journal = The Cochrane Database of Systematic Reviews | volume = 1 | pages = CD007393 | date = January 2017 | issue = 7 | pmid = 28085183 | pmc = 6464756 | doi = 10.1002/14651858.CD007393.pub4 }}</ref>

Evidence supports the use of [[cannabinoids]] for some forms of neuropathic pain.<ref name="Hill2015">{{cite journal | vauthors = Hill KP | title = Medical Marijuana for Treatment of Chronic Pain and Other Medical and Psychiatric Problems: A Clinical Review | journal = JAMA | volume = 313 | issue = 24 | pages = 2474–83 | date = June 2015 | pmid = 26103031 | doi = 10.1001/jama.2015.6199 | quote = Use of marijuana for chronic pain, neuropathic pain, and spasticity due to multiple sclerosis is supported by high-quality evidence }}</ref> A 2018 Cochrane review of cannabis-based medicines for the treatment of chronic neuropathic pain included 16 studies. All of these studies included [[Tetrahydrocannabinol|THC]] as a pharmacological component of the test group. The authors rated the quality of evidence as very low to moderate. The primary outcome was quoted as, "[[Cannabis (drug)|Cannabis]]-based medicines may increase the number of people achieving 50% or greater pain relief compared with placebo" but "the evidence for improvement in Patient Global Impression of Change (PGIC) with cannabis to be of very low quality". The authors also conclude, "The potential benefits of cannabis-based medicine... might be outweighed by their potential harms."<ref>{{cite journal | vauthors = Mücke M, Phillips T, Radbruch L, Petzke F, Häuser W | title = Cannabis-based medicines for chronic neuropathic pain in adults | journal = The Cochrane Database of Systematic Reviews | volume = 3 | pages = CD012182 | date = March 2018 | issue = 7 | pmid = 29513392 | pmc = 6494210 | doi = 10.1002/14651858.CD012182.pub2 }}</ref>

A 2014 Cochrane review of topical [[lidocaine]] for the treatment of various peripheral neuropathies found its usage supported by a few low-quality studies. The authors state that no high-quality randomised control trials demonstrate its efficacy or safety profile.<ref>{{cite journal | vauthors = Derry S, Wiffen PJ, Moore RA, Quinlan J | editor1-first = Sheena | editor1-last = Derry | title = Topical lidocaine for neuropathic pain in adults | journal = The Cochrane Database of Systematic Reviews | issue = 7 | pages = CD010958 | date = July 2014 | volume = 2014 | pmid = 25058164 | pmc = 6540846 | doi = 10.1002/14651858.CD010958.pub2 }}</ref>

A 2015 (updated in 2022) Cochrane review of topical [[clonidine]] for the treatment of diabetic neuropathy included two studies of 8 and 12 weeks in length; both of which compared topical clonidine to placebo and both of which were funded by the same drug manufacturer. The review found that topical clonidine may provide some benefit versus placebo. However, the authors state that the included trials are potentially subject to significant bias and that the evidence is of low to moderate quality.<ref>{{Cite journal |last1=Serednicki |first1=Wojciech T. |last2=Wrzosek |first2=Anna |last3=Woron |first3=Jaroslaw |last4=Garlicki |first4=Jaroslaw |last5=Dobrogowski |first5=Jan |last6=Jakowicka-Wordliczek |first6=Joanna |last7=Wordliczek |first7=Jerzy |last8=Zajaczkowska |first8=Renata |date=2022-05-19 |title=Topical clonidine for neuropathic pain in adults |journal=The Cochrane Database of Systematic Reviews |volume=2022 |issue=5 |pages=CD010967 |doi=10.1002/14651858.CD010967.pub3 |issn=1469-493X |pmc=9119025 |pmid=35587172}}</ref>

A 2007 Cochrane review of [[aldose reductase inhibitor]]s for the treatment of pain deriving from diabetic polyneuropathy found it no better than a placebo.<ref>{{cite journal | vauthors = Chalk C, Benstead TJ, Moore F | title = Aldose reductase inhibitors for the treatment of diabetic polyneuropathy | journal = The Cochrane Database of Systematic Reviews | issue = 4 | pages = CD004572 | date = October 2007 | volume = 2010 | pmid = 17943821 | doi = 10.1002/14651858.CD004572.pub2 | pmc = 8406996 }}</ref>

===Medical devices===
[[Transcutaneous electrical nerve stimulation]] (TENS) therapy is often used to treat various types of neuropathy. A 2010 review of three trials, for the treatment of diabetic neuropathy explicitly, involving a total of 78 patients found some improvement in pain scores after 4 and 6 but not 12 weeks of treatment and an overall improvement in neuropathic symptoms at 12 weeks.<ref>{{cite journal | vauthors = Jin DM, Xu Y, Geng DF, Yan TB | title = Effect of transcutaneous electrical nerve stimulation on symptomatic diabetic peripheral neuropathy: a meta-analysis of randomized controlled trials | journal = Diabetes Research and Clinical Practice | volume = 89 | issue = 1 | pages = 10–5 | date = July 2010 | pmid = 20510476 | doi = 10.1016/j.diabres.2010.03.021 }}</ref> Another 2010 review of four trials, for the treatment of diabetic neuropathy, found significant improvement in pain and overall symptoms, with 38% of patients in one trial becoming asymptomatic. The treatment remains effective even after prolonged use, but symptoms return to baseline within a month of cessation of treatment.<ref>{{cite journal | vauthors = Pieber K, Herceg M, Paternostro-Sluga T | title = Electrotherapy for the treatment of painful diabetic peripheral neuropathy: a review | journal = Journal of Rehabilitation Medicine | volume = 42 | issue = 4 | pages = 289–95 | date = April 2010 | pmid = 20461329 | doi = 10.2340/16501977-0554 | doi-access = free }}</ref>

These older reviews can be balanced with a more recent 2017 review of TENS for neuropathic pain by Cochrane which concluded that "This review is unable to state the effect of TENS versus sham TENS for pain relief due to the very low quality of the included evidence... The very low quality of evidence means we have very limited confidence in the effect estimate reported." A very low quality of evidence means, 'multiple sources of potential bias' with a 'small number and size of studies'.<ref>{{cite journal | vauthors = Gibson W, Wand BM, O'Connell NE | title = Transcutaneous electrical nerve stimulation (TENS) for neuropathic pain in adults | journal = The Cochrane Database of Systematic Reviews | volume = 9 | pages = CD011976 | date = September 2017 | issue = 3 | pmid = 28905362 | pmc = 6426434 | doi = 10.1002/14651858.CD011976.pub2 }}</ref>

===Surgery===
{{Main article|Nerve decompression}}
Peripheral neuropathy due to [[Nerve compression syndrome|nerve compression]] is treatable with a [[nerve decompression]].<ref name=":13">{{cite journal |vauthors=Kay J, de Sa D, Morrison L, Fejtek E, Simunovic N, Martin HD, Ayeni OR |date=December 2017 |title=Surgical Management of Deep Gluteal Syndrome Causing Sciatic Nerve Entrapment: A Systematic Review |url= |journal=Arthroscopy |volume=33 |issue=12 |pages=2263–2278.e1 |doi=10.1016/j.arthro.2017.06.041 |pmid=28866346}}</ref><ref name=":14">{{cite journal |vauthors=ElHawary H, Barone N, Baradaran A, Janis JE |date=February 2022 |title=Efficacy and Safety of Migraine Surgery: A Systematic Review and Meta-analysis of Outcomes and Complication Rates |url= |journal=Ann Surg |volume=275 |issue=2 |pages=e315–e323 |doi=10.1097/SLA.0000000000005057 |pmid=35007230}}</ref><ref>{{cite journal |vauthors=Giulioni C, Pirola GM, Maggi M, Pitoni L, Fuligni D, Beltrami M, Palantrani V, De Stefano V, Maurizi V, Castellani D, Galosi AB |date=March 2024 |title=Pudendal Nerve Neurolysis in Patients Afflicted With Pudendal Nerve Entrapment: A Systematic Review of Surgical Techniques and Their Efficacy |url= |journal=Int Neurourol J |volume=28 |issue=1 |pages=11–21 |doi=10.5213/inj.2448010.005 |pmc=10990758 |pmid=38569616}}</ref><ref>{{cite journal |vauthors=Lu VM, Burks SS, Heath RN, Wolde T, Spinner RJ, Levi AD |date=January 2021 |title=Meralgia paresthetica treated by injection, decompression, and neurectomy: a systematic review and meta-analysis of pain and operative outcomes |url= |journal=J Neurosurg |volume=135 |issue=3 |pages=912–922 |doi=10.3171/2020.7.JNS202191 |pmid=33450741}}</ref> When a nerve is subject to localized pressure or stretching, the vascular supply is interrupted leading to a [[Pathophysiology of nerve entrapment|cascade of physiological changes]] that causes [[nerve injury]].<ref>{{cite journal |vauthors=Lundborg G, Dahlin LB |date=May 1996 |title=Anatomy, function, and pathophysiology of peripheral nerves and nerve compression |url= |journal=Hand Clin |volume=12 |issue=2 |pages=185–93 |doi= |pmid=8724572}}</ref> In a nerve decompression, a surgeon explores the entrapment site and removes tissue around the nerve to relieve pressure. Common sites of entrapment are spaces of anatomic narrowing such as osteofibrous tunnels (e.g. [[carpal tunnel]] in [[carpal tunnel syndrome]]).<ref>{{cite journal |vauthors=Schmid AB, Fundaun J, Tampin B |date=2020 |title=Entrapment neuropathies: a contemporary approach to pathophysiology, clinical assessment, and management |url= |journal=Pain Rep |volume=5 |issue=4 |pages=e829 |doi=10.1097/PR9.0000000000000829 |pmc=7382548 |pmid=32766466}}</ref> In many cases the potential for nerve recovery (full or partial) after decompression is excellent, as chronic nerve compression is associated with low-grade nerve injury ([[Nerve injury classification|Sunderland classification]] I-III) rather than high-grade nerve injury (Sunderland classification IV-V).<ref>{{cite journal |vauthors=Mackinnon SE |date=May 2002 |title=Pathophysiology of nerve compression |url= |journal=Hand Clin |volume=18 |issue=2 |pages=231–41 |doi=10.1016/s0749-0712(01)00012-9 |pmid=12371026}}</ref> Nerve decompressions for properly selected patients are associated with a significant reduction in pain, in some cases the complete elimination of pain.<ref>{{cite journal |vauthors=Louie D, Earp B, Blazar P |date=September 2012 |title=Long-term outcomes of carpal tunnel release: a critical review of the literature |url= |journal=Hand (N Y) |volume=7 |issue=3 |pages=242–6 |doi=10.1007/s11552-012-9429-x |pmc=3418353 |pmid=23997725}}</ref><ref name=":13" /><ref name=":14" />

In people with [[Diabetic neuropathy|diabetic peripheral neuropathy]], two reviews make a case for nerve decompression surgery as an effective means of pain relief and support claims for protection from foot ulceration.<ref name="Nickerson2017">{{cite journal |vauthors=Nickerson DS |title=Nerve decompression and neuropathy complications in diabetes: Are attitudes discordant with evidence? |journal=Diabet Foot Ankle |volume=8 |issue=1 |pages=1367209 |date=2017 |pmid=28959382 |pmc=5613909 |doi=10.1080/2000625X.2017.1367209 |url=}}</ref><ref name="Tu2017">{{cite journal |vauthors=Tu Y, Lineaweaver WC, Chen Z, Hu J, Mullins F, Zhang F |title=Surgical Decompression in the Treatment of Diabetic Peripheral Neuropathy: A Systematic Review and Meta-analysis |journal=J Reconstr Microsurg |volume=33 |issue=3 |pages=151–57 |date=March 2017 |pmid=27894152 |doi=10.1055/s-0036-1594300 |s2cid=22825614 |url=}}</ref> There is less evidence for efficacy of surgery for non-diabetic peripheral neuropathy of the legs and feet. One uncontrolled study that did before/after comparisons with a minimum of one-year follow-up reported improvements in pain relief, impaired balance, and numbness. "There was no difference in outcomes between patients with diabetic versus idiopathic neuropathy in response to nerve decompression."<ref name="Valdivia2013" /> There are no placebo-controlled trials for idiopathic peripheral neuropathy in the published scientific literature.

===Diet===
According to a review, [[gluten-free diet|strict gluten-free diet]] is an effective treatment when neuropathy is caused by gluten sensitivity, with or without the presence of digestive symptoms or intestinal injury.<ref name=ZisHadjivassiliou2019 />

=== Counselling ===
A 2015 review on the treatment of neuropathic pain with [[Psychotherapy|psychological therapy]] concluded that "There is insufficient evidence of the efficacy and safety of psychological interventions for chronic neuropathic pain. The two available studies show no benefit of treatment over either waiting list or placebo control groups."<ref>{{cite journal | vauthors = Eccleston C, Hearn L, Williams AC | title = Psychological therapies for the management of chronic neuropathic pain in adults | journal = The Cochrane Database of Systematic Reviews | issue = 10 | pages = CD011259 | date = October 2015 | volume = 2015 | pmid = 26513427 | pmc = 6485637 | doi = 10.1002/14651858.CD011259.pub2 }}</ref>

=== Alternative medicine ===
A 2019 Cochrane review of the treatment of [[Herbalism|herbal medicinal]] products for people with neuropathic pain for at least three months concluded that "There was insufficient evidence to determine whether [[nutmeg]] or [[Hypericum perforatum|St John's wort]] has any meaningful efficacy in neuropathic pain conditions. The quality of the current evidence raises serious uncertainties about the estimates of effect observed, therefore, we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect."<ref>{{cite journal | vauthors = Boyd A, Bleakley C, Hurley DA, Gill C, Hannon-Fletcher M, Bell P, McDonough S | title = Herbal medicinal products or preparations for neuropathic pain | journal = The Cochrane Database of Systematic Reviews | volume = 4 | pages = CD010528 | date = April 2019 | issue = 5 | pmid = 30938843 | pmc = 6445324 | doi = 10.1002/14651858.CD010528.pub4 }}</ref>

A 2017 Cochrane review on the usage of [[acupuncture]] as a treatment for neuropathic pain concludes, "Due to the limited data available, there is insufficient evidence to support or refute the use of acupuncture for neuropathic pain in general, or for any specific neuropathic pain condition when compared with sham acupuncture or other active therapies." Also, "Most studies included a small sample size (fewer than 50 participants per treatment arm) and all studies were at high risk of bias for blinding of participants and personnel." Also, the authors state, "we did not identify any study comparing acupuncture with treatment as usual."<ref>{{cite journal | vauthors = Ju ZY, Wang K, Cui HS, Yao Y, Liu SM, Zhou J, Chen TY, Xia J | title = Acupuncture for neuropathic pain in adults | journal = The Cochrane Database of Systematic Reviews | volume = 12 | pages = CD012057 | date = December 2017 | issue = 7 | pmid = 29197180 | pmc = 6486266 | doi = 10.1002/14651858.CD012057.pub2 }}</ref>

Alpha [[lipoic acid]] (ALA) with benfotiamine is a proposed pathogenic treatment for painful diabetic neuropathy only.<ref>{{Cite web|url=http://www.currentdiabetesreviews.com/articles/170231/review-of-diabetic-polyneuropathy-pathogenesis-diagnosis-and-management-according-to-the-consensus-of-egyptian-experts|title = Review of Diabetic Polyneuropathy: Pathogenesis, Diagnosis A}}</ref> The results of two systematic reviews state that oral ALA produced no clinically significant benefit, intravenous ALA administered over three weeks may improve symptoms and that long-term treatment has not been investigated.<ref>{{Cite journal|last1=Bartkoski|first1=Scott|last2=Day|first2=Margaret|date=2016-05-01|title=Alpha-Lipoic Acid for Treatment of Diabetic Peripheral Neuropathy|journal=American Family Physician|volume=93|issue=9|pages=786|issn=1532-0650|pmid=27175957}}</ref>