title: Curcumin exerts antinociceptive effects in a mouse model of neuropathic pain: descending monoamine system and opioid receptors are differentially involved.
abstract: Curcumin, a phenolic compound present in Curcuma longa, has been reported to exert antinociceptive effects in some animal models, but the mechanisms remain to be elucidated. This work aimed to investigate the antinociceptive action of curcumin on neuropathic pain and the underlying mechanism(s). Chronic constriction injury (CCI), a canonical animal model of neuropathic pain, was produced by loosely ligating the sciatic nerve in mice and von Frey hair or hot plate test was used to assess mechanical allodynia or thermal hyperalgesia (to heat), respectively. Chronic, but not acute, curcumin treatment (5, 15 or 45 mg/kg, p.o., twice per day for three weeks) alleviated mechanical allodynia and thermal hyperalgesia in CCI mice, accompanied by increasing spinal monoamine (or metabolite) contents. Chemical ablation of descending noradrenaline (NA) by 6-hydroxydopamine (6-OHDA), or depletion of descending serotonin by p-chlorophenylalanine (PCPA), abolished curcumin's antinociceptive effect on mechanical allodynia or thermal hyperalgesia, respectively. The anti-allodynic action of curcumin on mechanical stimuli was totally blocked by chronic co-treatment with the β(2)-adrenoceptor antagonist ICI 118,551, or by acute co-treatment with the delta-opioid receptor antagonist naltrindole. Meanwhile, co-treatment with the 5-HT(1A) receptor antagonist WAY-100635 chronically, or with the irreversible mu-opioid receptor antangonist β-funaltrexamine acutely, completely abrogated the anti-hyperalgesic action of curcumin on thermal stimuli. Collectively, these findings indicate that the descending monoamine system (coupled with spinal β(2)-adrenoceptor and 5-HT(1A) receptor) is critical for the modality-specific antinociceptive effect of curcumin in neuropathic pain. Delta- and mu-opioid receptors are likely rendered as downstream targets, accordingly. This article is part of a Special Issue entitled 'Post-Traumatic Stress Disorder'.
authors.affiliation: State Key Laboratory of Medical Neurobiology and Department of Pharmacology, Shanghai Medical College of Fudan University, Shanghai 200032, China. zhaoxin@nbu.edu.cn
authors.forename: Xin
authors.initials: X
authors.lastname: Zhao
authors.forename: Ying
authors.initials: Y
authors.lastname: Xu
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhao
authors.forename: Chang-Rui
authors.initials: CR
authors.lastname: Chen
authors.forename: Ai-Ming
authors.initials: AM
authors.lastname: Liu
authors.forename: Zhi-Li
authors.initials: ZL
authors.lastname: Huang
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use*; D003474:Curcumin / Q000494:pharmacology / Q000627:therapeutic use*; D006930:Hyperalgesia / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D008297:Male; D051379:Mice; D009292:Narcotic Antagonists / Q000494:pharmacology; D009437:Neuralgia / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D010147:Pain Measurement / Q000187:drug effects*; D010879:Piperazines / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D011957:Receptors, Opioid / Q000378:metabolism; D020426:Sciatic Neuropathy / Q000150:complications / Q000188:drug therapy / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D012702:Serotonin Antagonists / Q000494:pharmacology; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000319:Adrenergic beta-Antagonists; D000894:Anti-Inflammatory Agents, Non-Steroidal; D009292:Narcotic Antagonists; D010879:Piperazines; D011412:Propanolamines; D011725:Pyridines; D011957:Receptors, Opioid; D012702:Serotonin Antagonists; D012701:Serotonin; C026777:ICI 118551; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D003474:Curcumin; D009638:Norepinephrine