Purpose of Review
Many cultures throughout history have used cannabis to treat a variety of painful ailments. Neuropathic pain is a complicated condition that is challenging to treat with our current medications. Recent scientific discovery has elucidated the intricate role of the endocannabinoid system in the pathophysiology of neuropathic pain. As societal perceptions change, and legislation on medical cannabis relaxes, there is growing interest in the use of medical cannabis for neuropathic pain.
We examined current basic scientific research and data from recent randomized controlled trials (RCTs) evaluating medical cannabis for the treatment of neuropathic pain. These studies involved patients with diverse etiologies of neuropathic pain and included medical cannabis with different THC concentrations and routes of administration. Multiple RCTs demonstrated efficacy of medical cannabis for treating neuropathic pain, with number needed to treat (NNT) values similar to current pharmacotherapies.
Although limited by small sample sizes and short duration of study, the evidence appears to support the safety and efficacy of short-term, low-dose cannabis vaporization and oral mucosal delivery for the treatment of neuropathic pain. The results suggest medical cannabis may be as tolerable and effective as current neuropathic agents; however, more studies are needed to determine the long-term effects of medical cannabis use. Furthermore, continued research to optimize dosing, cannabinoid ratios, and alternate routes of administration may help to refine the therapeutic role of medical cannabis for neuropathic pain.
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van Hecke O, Austin SK, Khan RA, Smith BH, Torrance N. Neuropathic pain in the general population: a systematic review of epidemiological studies. Pain. 2014;155(4):654–62. https://doi.org/10.1016/j.pain2013.11.013. Epub 2013 Nov 26.
International Association for the Study of Pain (IASP) reference: IASP. Diagnosis and classification of neuropathic pain. Pain Clin Update. 2010;18(7):1–6.
McDermott AM, Toelle TR, Rowbotham DJ, Schaefer CP, Dukes EM. The burden of neuropathic pain: results from a cross-sectional survey. Eur J Pain. 2006;10(2):127–35. https://doi.org/10.1016/j.ejpain.2005.01.014.
Schaefer C, Mann R, Sadosky A, Daniel S, Parsons B, Nieshoff E, et al. Burden of illness associated with peripheral and central neuropathic pain among adults seeking treatment in the United States: a patient-centered evaluation. Pain Med. 2014;15(12):2105–19. https://doi.org/10.1111/pme.12502.
Schaefer C, Sadosky A, Mann R, Daniel S, Parsons B, Tuchman M, et al. Pain severity and the economic burden of neuropathic pain in the United States: BEAT Neuropathic Pain Observational Study. Clinicoecon Outcomes Res. 2014;6:483–96. https://doi.org/10.2147/CEOR.S63323. eCollection 2014.
Attal N, Fermanian C, Fermanian J, Lanteri-Minet M, Alchaar H, Bouhassira D. Neuropathic pain: are there distinct subtypes depending on the aetiology or anatomical lesion? Pain. 2008;138(2):343–53. https://doi.org/10.1016/j.pain.2008.01.006.
•• Baron R, Maier C, Attal N, Binder A, Bouhassira D, Cruccu G, et al. Peripheral neuropathic pain: a mechanism-related organizing principle based on sensory profiles. Pain. 2017;158(2):261–72. https://doi.org/10.1097/j.pain.0000000000000753. This study used database analysis of patients with neuropathic pain to identify subgroups of neuropathic pain based on characteristic sensory profiles. The authors hypothesize that these subgroup profiles may be related to pathophysiological mechanisms and maybe useful for subgroup analysis of responders versus non-responders of neuropathic pain therapies in clinical trials.
Yaksh TL, Wiese AJA. Survey of systems involved in nociceptive processing. In: Deer TR, Leong MS, Buvanendran A, Gordin V, Kim PS, Panchal SJ, Ray A, editors. Comprehensive treatment of chronic pain by medical, interventional, and integrative approaches. Berlin: Springer. The American Academy of Pain Medicine Textbook on Pain Management; 2014.
Wall PD, Devor M. Sensory afferent impulses originate from dorsal root ganglia as well as the periphery in normal and nerve injured rats. Pain. 1983;17(4):321–39. https://doi.org/10.1016/0304-3959(83)90164-1.
Seltzer Z, Devor M. Ephaptic transmission in chronically damaged peripheral nerves. Neurology. 1979;29(7):1061–4. https://doi.org/10.1212/WNL.29.7.1061.
Hong S, Morrow TJ, Paulso PE, Isom LL, Wiley JW. Early painful diabetic neuropathy is associated with differential changes in tetrodotoxin-sensitive and –resistant sodium channels in dorsal root ganglion neurons in the rat. J Biol Chem. 2004;279(28):29341–50. https://doi.org/10.1074/jbc.M404167200.
Ma W, Zhang Y, Bantel C, Eisenach JC. Medium and large injured dorsal root ganglion cells increase TRPV-1, accompanied by increased alpha2c-adrenoceptor co-expression and functional inhibition by clonidine. Pain. 2005;113(3):386–94. https://doi.org/10.1016/j.pain.2004.11.018.
Price TJ, Cervero F, de Koninck Y. Role of cation-chloride-cotransporters (CCC) in pain and hyperalgesia. Curr Top Med Chem. 2005;5(6):547–55. https://doi.org/10.2174/1568026054367629.
Thakor DK, Lin A, Matsuka Y, Meyer EM, Ruangsri S, Nishimura I, et al. Increased peripheral nerve excitability and local NaV1.8 mRNA up-regulation in painful neuropathy. Mol Pain. 2009;5:14. https://doi.org/10.1186/1744-8069-5-14.
Takeda M, Tsuboi Y, Kitagawa J, Nakagawa K, Iwata K, Matsumoto S. Potassium channels as a potential therapeutic target for trigeminal neuropathic and inflammatory pain. Mol Pain. 2011;7:5. https://doi.org/10.1186/1744-8069-7-5.
Zhou C, Luo ZD. Nerve injury – induced calcium channel alpha-2-delta-1 protein dysregulation leads to increased pre-synaptic excitatory input into deep dorsal horn neurons and neuropathic allodynia. Eur J Pain. 2015;19(9):1267–76. https://doi.org/10.1002/ejp.656.
Misawa S, Sakurai K, Shibuya K, Isose S, Kanai K, Ogino J, et al. Neuropathic pain is associated with increased nodal persistent Na(+) currents in human diabetic neuropathy. J Peripher Nerv Syst. 2009;14(4):279–84. https://doi.org/10.1111/j.1529-8027.2009.00239.x.
Fischer MJ, Reeh PW. Sensitization to heat through G-protein-coupled receptor pathways in the isolated sciatic mouse nerve. Eur J Neurosci. 2007;25(12):3570–5. https://doi.org/10.1111/j.1460-9568.2007.05582.x.
Shinder V, Govrin-Lippmann R, Cohen S, Belenky M, Ilin P, Fried K. Structural basis of sympathetic-sensory coupling in rat and human dorsal root ganglia following peripheral nerve injury. J Neurocytol. 1999;28(9):743–61. https://doi.org/10.1023/A:1007090105840.
Vallejo R, Tilley DM, Vogel L, Benyamin R. The role of glia and the immune system in the development and maintenance of neuropathic pain. Pain Pract. 2010;10(3):167–84. https://doi.org/10.1111/j.1533-2500.2010.000367.x.
Ossipov MH, Dussor GO, Porreca F. Central modulation of pain. J Clin Invest. 2010;120(11):3779–87. https://doi.org/10.1172/JCI43766.
Wakaizumi K, Kondo T, Hamada Y, Narita M, Kawabe R, Narita H. Involvement of mesolimbic dopaminergic network in neuropathic pain relief by treadmill exercise: a study for specific neural control with Gi-DREADD in mice. Mol Pain. 2016;12. Print 2016.
•• Finnerup NB, Attal N, Haroutounian S, McNicol E, Baron R, Dworkin RH, et al. Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis. Lancet Neurol. 2015;14(2):162–73. https://doi.org/10.1016/S1474-4422(14)70251-0. A meta-analysis of 229 RCTs evaluated the efficacy of many of the accepted treatments for neuropathic pain calculating NNT, NNH and GRADE recommendation for each therapy.
•• Maldonado R, Baños JE, Cabañero D. The endocannabinoid system and neuropathic pain. Pain. 2016;157(Suppl 1):S23–32. https://doi.org/10.1097/j.pain.0000000000000428. An informative article on the endocannabinoid system and its role in the pathophysiology of neuropathic pain. Discusses current basic science research and examines data from preclinical animal studies and clinical trials.
•• Andraea MH, Carter GM, Shaparin N, Suslov K, Ellis RJ, Ware MA, et al. Inhaled cannabis for chronic neuropathic pain: a meta-analysis of individual patient data. J Pain. 2015;16(12):1221–32. https://doi.org/10.1016/j.jpain.2015.07.009. A novel Bayesian meta-analysis that included data from 5 RCTs studying the efficacy of inhaled cannabis for chronic neuropathic pain. Results a suggested inhaled cannabis has a NNT of 5.6 for neuropathic pain.
Zuardi AW. History of cannabis as a medicine: a review. Rev Bras Psiquiatr. 2006;28(2):153–7. https://doi.org/10.1590/S1516-44462006000200015.
Wood GW, Bache F. The dispensatory of the United States of America, vol. 1238. 6th ed. Philadelphia: Grigg and Elliot; 1845.
Furnish TJ, Wallace MS. Marijuana and cannabinoids for pain. In: Staat PS, Silverman SM, editors. Controlled substance management in chronic pain: a balanced approach. Switzerland: Springer International; 2016.
Scotter EL, Abood ME, Glass M. The endocannabinoid system as a target for the treatment of neurodegenerative disease. Br J Pharmacol. 2010;160(3):480–98. https://doi.org/10.1111/j.1476-5381.2010.00735.x.
Russo EB, Hohmann AG. Role of cannabinoids in pain management. In: Deer TR, Leong MS, Buvanendran A, Gordin V, Kim PS, Panchal SJ, Ray AL, editors. Comprehensive treatment of chronic pain by medical, interventional, and integrative approaches. Berlin: Springer. The American Academy of Pain Medicine Textbook on Pain Management; 2014.
Wang J, Ueda N. Biology of endocannabinoid synthesis system. Prostaglandins Other Lipid Mediat. 2009;89(3–4):112–9. https://doi.org/10.1016/j.prostaglandins.2008.12.002.
Devane WA, Dysarz FA 3rd, Johnson MR, Melvin LS, Howlett AC. Determination and characterization of a cannabinoid receptor in rat brain. Mol Pharmacol. 1988;34(5):605–13.
Jensen B, Chen J, Furnish T, Wallace M. Medical marijuana and chronic pain: a review of basic science and clinical evidence. Curr Pain Headache Rep. 2015;19(10):50. https://doi.org/10.1007/s11916-015-0524-x.
Fine PG, Rosenfeld MJ. Cannabinoids for neuropathic pain. Curr Pain Headache Rep. 2014;18(10):451. https://doi.org/10.1007/s11916-014-0451-2.
Rácz I, Nent E, Erxlebe E, Zimmer A. CB1 receptors modulate affective behaviour induced by neuropathic pain. Brain Res Bull. 2015;114:42–8. https://doi.org/10.1016/j.brainresbull.2015.03.005.
Gaetani S, Dipasquale P, Romano A, Righetti L, Cassano T, Piomelli D, et al. The endocannabinoid system as a target for novel anxiolytic and antidepressant drugs. Int Rev Neurobiol. 2009;85:57–72. https://doi.org/10.1016/S0074-7742(09)85005-8.
Devane WA, Hanus L, Breuer A, Pertwee RG, Stevenson LA, Griffin G, et al. Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science. 1992;258(5090):1946–9. https://doi.org/10.1126/science.1470919.
Munro S, Thomas KL, Abu-Shaar M. Molecular characterization of a peripheral receptor for cannabinoids. Nature. 1993;365(6441):61–5. https://doi.org/10.1038/365061a0.
Racz I, Nadal X, Alferink J, Baños JE, Rehnelt J, Martín M, et al. Crucial role of CB(2) cannabinoid receptor in the regulation of central immune responses during neuropathic pain. J Neurosci. 2008;28(46):12125–35. https://doi.org/10.1523/Jneurosc.3400-08.2008.
Guindon J, Hohmann AG. Cannabinoid CB2 receptors: a therapeutic target for the treatment of inflammatory and neuropathic pain. Br J Pharmacol. 2008;153(2):319–34. https://doi.org/10.1038/sj.bjp.0707531.
Agarwal N, Pacher P, Tegeder I, Amaya F, Constantin CE, Brenner GJ, et al. Cannabinoids mediate analgesia largely via peripheral type 1 cannabinoid receptors in nociceptors. Nat Neurosci. 2007;10(7):870–9. https://doi.org/10.1038/nn1916.
Nadal X, La Porta C, Andreea Bura S, Maldonado R. Involvement of the opioid and cannabinoid systems in pain control: new insights from knockout studies. Eur J Pharmacol. 2013;716(1–3):142–57. https://doi.org/10.1016/j.ejphar.2013.01.077.
Wotherspoon G, Fox A, McIntyre P, Colley S, Bevan S, Winter J. Peripheral nerve injury induces cannabinoid receptor 2 protein expression in rat sensory neurons. Neuroscience. 2005;135(1):235–45. https://doi.org/10.1016/j.neuroscience.2005.06.009.
Clapper JR, Moreno-Sanz G, Russo R, Guijarro A, Vacondio F, Duranti A, et al. Anandamide suppresses pain initiation through a peripheral endocannabinoid mechanism. Nat Neurosci. 2010;13(10):1265–70. https://doi.org/10.1038/nn.2632.
Babayeva M, Assefa H, Basu P, Chumki S, Loewy Z. Marijuana compounds: a nonconventional approach to Parkinson’s disease therapy. Parkinson’s Dis. 2016;2016:1279042–19. https://doi.org/10.1155/2016/1279042.
Nadulski T, Pragst F, Weinberg G, Roser P, Schnelle M, Fronk EM, et al. Randomized, double-blind, placebo-controlled study about the effects of cannabdiol (CBD) on the pharmacokinetics of Delta9-tetrahydrocannabinol (THC) after oral application of THC verses standardized cannabis extract. Ther Drug Monit. 2005;27(6):799–810. https://doi.org/10.1097/01.ftd.0000177223.19294.5c.
Braida D, Pozzi M, Cavallini R, Sala M. Conditioned place preference induced by the cannabinoid agonist CP 55,940: interaction with the opioid system. Neuroscience. 2001;104(4):923–6. https://doi.org/10.1016/S0306-4522(01)00210-X.
Reilly D, Didcott P, Swift W, Hall W. Long-term cannabis use: characteristics of users in an Australian rural area. Addiction. 1998;93(6):837–46. https://doi.org/10.1046/j.1360-0443.1998.9368375.x.
Wallace M, Schulteis G, Atkinson JH, Wolfson T, Lazzaretto D, Bentley H, et al. Dose-dependent effects of smoked cannabis on capsaicin-induced pain and hyperalgesia in healthy volunteers. Anesthesiology. 2007;107(5):785–96. https://doi.org/10.1097/01.anes.0000286986.92475.b7.
Portenoy RK, Ganae-Motan ED, Allende S, Yanagihara R, Shaiova L, Weinstein S, et al. Nabiximols for opioid- treated cancer patients with poorly-controlled chronic pain: a randomized, placebo-controlled, graded-dose trial. J Pain. 2012;13(5):438–49. https://doi.org/10.1016/j.jpain.2012.01.003.
Savage SR, Romero-Sandoval A, Schatman M, Wallace M, Fanciullo G, McCarberg B, et al. Cannabis in pain treatment: clinical and research considerations. J Pain. 2016;17(6):654–68. https://doi.org/10.1016/j.jpain.2016.02.007.
Hampson AJ, Bornheim LM, Scanziani M, Yost CS, Gray AT, Hansen BM, et al. Dual effects of anandamide on NMDA receptor-mediated responses and neurotransmission. J Neurochem. 1998;70(2):671–6.
Abrams DI, Jay CA, Shade SB, Vizoso H, Reda H, Press S, et al. Cannabis in painful HIV-associated sensory neuropathy: a randomized placebo-controlled trial. Neurology. 2007;68(7):515–21. https://doi.org/10.1212/01.wnl.0000253187.66183.9c.
Ellis RJ, Toperoff W, Vaida F, van den Brande G, Gonzales J, Gouaux B, et al. Smoked medicinal cannabis for neuropathic pain in HIV: a randomized, crossover clinical trial. Neuropsychopharmacology. 2009;34(3):672–80. https://doi.org/10.1038/npp.2008.120.
Wilsey B, Marcotte T, Tsodikov A, Millman J, Bentley H, Gouaux B, et al. Randomized, placebo-controlled, crossover trial of cannabis cigarettes in neuropathic pain. J Pain. 2008;9(6):506–21. https://doi.org/10.1016/j.jpain.2007.12.010.
Ware MA, Wang T, Shapiro S, Robinson A, Ducruet T, Huynh T, et al. Smoked cannabis for chronic neuropathic pain: a randomized controlled trial. CMAJ. 2010;182(14):E694–701. https://doi.org/10.1503/cmaj.091414.
•• Wilsey B, Marcotte T, Deutsch R, Gouaux B, Sakai S, Donaghe H. Low-dose vaporized cannabis significantly improves neuropathic pain. J Pain. 2013;14(2):136–48. https://doi.org/10.1016/j.jpain.2012.10.009. A RCT that demonstrated analgesia with low-dose vaporized cannabis.
Wilsey B, Marcotte TD, Deutsch R, Zhao H, Prasad H, Phan A. An exploratory human laboratory experiment evaluating vaporized cannabis in the treatment of neuropathic pain from spinal cord injury and disease. J Pain. 2016;17(9):982–1000. https://doi.org/10.1016/j.jpain.2016.05.010.
•• Wallace MS, Marcotte TD, Umlauf A, Gouaux B, Atkinson JH. Efficacy of inhaled cannabis on painful diabetic neuropathy. J Pain. 2015;16(7):616–27. https://doi.org/10.1016/j.jpain.2015.03.008. RCT that demonstrated efficacy of vaporized cannabis delivery in patients with painful diabetic neuropathy.
•• Abrams DI, et al. Vaporization as a smokeless cannabis delivery system: a pilot study. Clin Pharmacol Ther. 2007;82(5):572–8. Study that demonstrated safety of cannabis vaporization.
Wade DT, Robson P, House H, Makela P, Aram JA. Preliminary controlled study to determine whether whole –plant cannabis extracts can improve intractable neurologic symptoms. Clin Rehabil. 2003;17(1):21–9. https://doi.org/10.1191/0269215503cr581oa.
• Berman JS, Symonds C, Birch R. Efficacy of two cannabis based medicinal extracts for relief of central neuropathic pain from brachial plexus avulsion: results of a randomized controlled trial. Pain. 2004;112(3):299–306. Randomized, double-blind, placebo-controlled crossover investigating efficacy of oromucousal THC:CBD (1:1) in chronic neuropathic pain secondary to brachial plexus root avulsion. Results were significant for improvement in sleep and mean pain severity score, but did not reach the goal of two point pain reduction, which was the primary outcome measure.
• Rog DJ, Nurmikko TJ, Friede T, Young CA. Randomized, controlled trial of cannabis-based medicine in central pain in multiple sclerosis. Neurology. 2005;65(6):812–9. Randomized, double-blind, placebo-controlled, parallel group trial in patients with MS and central neuropathic pain treated with oromucousal THC:CBD. Results demonstrated significant differences between cannabis based oromucousal spray and placebo in pain numerical rating and sleep disturbance in favor of cannabis based spray.
• Nurmikko TJ, Serpell MG, Hoggart B, Toomey PJ, Morlion BJ, Haines D. Sativex successfully treats neuropathic pain characterized by allodynia: a randomized, double-blind, placebo-controlled clinical trial. Pain. 2007;133(1–3):210–20. Randomized, double-blind, placebo-controlled, parallel group trial in patients with peripheral neuropathic pain treated with oromucousal THC:CBD spray. Results demonstrated significant changes in pain intensity scores, sleep index, and patient’s global impression of change in favor of the cannabis based spray.
GW Pharmaceuticals Ltd. https://www.gwpharm.com/products-pipeline/sativex/prescriber-information-full. Accessed Feb 14 2017.
• Langford RM, Mares J, Novotna A, Vachova M, Novakova I, Notcutt W, et al. A double-blind, randomized, placebo-controlled, parallel-group study of THC/CBD oromucosal spray in combination with the existing treatment regime in the relief of central neuropathic pain in patients with multiple sclerosis. J Neurol. 2013;260(4):984–97. https://doi.org/10.1007/s00415-012-6739-4. Randomized, double-blind, placebo-controlled, parallel group trial and withdrawal study in patients with multiple sclerosis and central neuropathic pain treated with oromucousal THC:CBD spray. Results during the treatment phase were equivocal, but there was in increased time to treatment failure in patients in the THC:CBD oromucousal spray group compared to placebo.
•• Serpell M, Ratcliffe S, Hovorka J, Schofield M, Taylor L, Lauder H, et al. A double-blind, randomized, placebo –controlled, parallel group study of THC/CBD spray in peripheral neuropathic pain treatment. Eur J Pain. 2014;18(7):999–1012. https://doi.org/10.1002/j.1532-2149.2013.00445.x. A double blind, randomized, placebo-controlled, parallel group study in patients with non-diabetic peripheral neuropathic pain with allodynia who were treated with THC:CBD oromucousal spray. Results demonstrated statistically significant decreases in 30% responder level, sleep quality, and global impression of change. Reductions in mean peripheral neuropathic pain scores were lower in the treatment group but failed to reach statistical significance.
Rog DJ, Nurmikko TJ, Young CA. Oromucosal delta9-tetrahydrocannabinol/cannabidiol for neuropathic pain associated with multiple sclerosis: an uncontrolled, open-label, 2 year extension trial. Clin Ther. 2007;29(9):2068–79. https://doi.org/10.1016/j.clinthera.2007.09.013.
Hoggart B, Ratcliffe S, Ehler E, Simpson KH, Hovorka J, Lejcko J, et al. A multicenter, open-label, follow-on study to assess the long-term maintenance of effect, tolerance and safety of THC/CBD oromucosal spray in the management of neuropathic pain. J Neurol. 2015;262(1):27–40. https://doi.org/10.1007/s00415-014-7502-9.
• GW Pharmaceuticals Ltd. NCT00710424. A double blind, randomized, placebo controlled, parallel group study of Sativex in the treatment of subjects with pain due to diabetic neuropathy. In: ClinicalTrials.gov (Internet). Bethesda (MD): National Library of Medicine (US). http://clinicaltrials.gov/show/NCT00710424 2006. 2000. Randomized, double-blind, placebo-controlled, parallel group study in patients with painful diabetic peripheral neuropathy treated with oromucousal CBD:THC spray. The results did not demonstrate significant changes in pain severity score or number of 30% improvement responders between treatment and placebo groups.
Selvarajah D, Gandhi R, Emery CJ, Tesfaye S. Randomized placebo-controlled double blind clinical trial of cannabis-based medicinal product (Sativex) in painful diabetic neuropathy: depression is a major confounding factor. Diabetes Care. 2010;33(1):128–30. https://doi.org/10.2337/dc09-1029.
Deshpande A, Mailis-Gagnon A, Zoheiry N, Lakha SF. Efficacy and adverse effects of medical marijuana for chronic noncancer pain: systematic review of randomized controlled trials. Can Fam Physician. 2015;61(8):e372–81.
Wang T, Collet JP, Shapiro S, Ware MA. Adverse effects of medical cannabinoids: a systematic review. CMAJ. 2008;178(13):1669–78. https://doi.org/10.1503/cmaj.071178.
Pletcher MJ, Vittinghoff E, Kalhan R, Richman J, Safford M, Sidney S, et al. Association between marijuana exposure and pulmonary function over 20 years. JAMA. 2012;307(2):173–81. https://doi.org/10.1001/jama.2011.1961.
National Academies of Sciences, Engineering, and Medicine (US); Health and Medicine Division (US); Board on Population Health and Public Health Practice (US); Committee on the Health Effects of Marijuana: An Evidence Review and Research Agenda (US). Editors. The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research. Washington (DC): National Academies Press (US); 2017.
Wallace MS, Ware MA. Medicinal marijuana: here to stay and time to take responsibility. Clin J Pain. 2015;31(11):931–2. https://doi.org/10.1097/AJP.0000000000000217.
Conflict of Interest
Gemayel Lee, Brittany Grovey, Tim Furnish, and Mark Wallace declare no conflict of interest.
Human and Animal Rights and Informed Consent
All reported studies/experiments with human or animal subjects performed by the authors have been previously published and complied with all applicable ethical standards (including the Helsinki declaration and its amendments, institutional/national research committee standards, and international/national/institutional guidelines).
This article is part of the Topical Collection on Neuropathic Pain