RATIONALE: Comorbid depression is commonly observed in individuals who suffer from neuropathic pain, which necessitates improved treatment. Curcumin, a phenolic compound derived from Curcuma longa, possesses both antinociceptive and antidepressant-like activities in animal studies, suggesting its possible usefulness in treating this comorbidity. OBJECTIVE: We investigated the effect of curcumin on depressive-like behaviors in mice with mononeuropathy, and explored the mechanism(s). METHODS: Chronic constriction injury (CCI) was produced by loosely ligating the sciatic nerves in mice. The nociceptive behaviors were examined using Hargreaves test, and the depressive-like behaviors were determined by forced swim test (FST) and tail suspension test (TST). RESULTS: After CCI injury, the neuropathic mice developed nociceptive and depressive-like behaviors, as shown by thermal hyperalgesia in Hargreaves test and protracted immobility time in FST and TST. Chronic treatment of neuropathic mice with curcumin (45 mg/kg, p.o., twice per day for 3 weeks) corrected their exacerbated nociceptive and depressive-like behaviors, which was abolished by chemical depletion of brain serotonin rather than noradrenaline. The paralleled antinociceptive and antidepressant-like actions of curcumin seem to be pharmacologically segregated, since intrathecal and intracerebroventricular injection of methysergide, a nonselective 5-HT receptor antagonist, separately counteracted the two actions of curcumin. Further, this antidepression was abrogated by repeated co-treatment with 5-HT1A receptor antagonist WAY-100635 and greatly attenuated by acute co-treatment with GABAA receptor antagonist bicuculline. CONCLUSION: Curcumin can normalize the depressive-like behaviors of neuropathic mice, which may be independent of the concurrent analgesic action and possibly mediated via the supraspinal serotonergic system and downstream GABAA receptor.
RATIONALE: Comorbid depression is commonly observed in individuals who suffer from neuropathic pain, which necessitates improved treatment. Curcumin, a phenolic compound derived from Curcuma longa, possesses both antinociceptive and antidepressant-like activities in animal studies, suggesting its possible usefulness in treating this comorbidity. OBJECTIVE: We investigated the effect of curcumin on depressive-like behaviors in mice with mononeuropathy, and explored the mechanism(s). METHODS:Chronic constriction injury (CCI) was produced by loosely ligating the sciatic nerves in mice. The nociceptive behaviors were examined using Hargreaves test, and the depressive-like behaviors were determined by forced swim test (FST) and tail suspension test (TST). RESULTS: After CCI injury, the neuropathicmice developed nociceptive and depressive-like behaviors, as shown by thermal hyperalgesia in Hargreaves test and protracted immobility time in FST and TST. Chronic treatment of neuropathicmice with curcumin (45 mg/kg, p.o., twice per day for 3 weeks) corrected their exacerbated nociceptive and depressive-like behaviors, which was abolished by chemical depletion of brain serotonin rather than noradrenaline. The paralleled antinociceptive and antidepressant-like actions of curcumin seem to be pharmacologically segregated, since intrathecal and intracerebroventricular injection of methysergide, a nonselective 5-HT receptor antagonist, separately counteracted the two actions of curcumin. Further, this antidepression was abrogated by repeated co-treatment with 5-HT1A receptor antagonist WAY-100635 and greatly attenuated by acute co-treatment with GABAA receptor antagonist bicuculline. CONCLUSION:Curcumin can normalize the depressive-like behaviors of neuropathicmice, which may be independent of the concurrent analgesic action and possibly mediated via the supraspinal serotonergic system and downstream GABAA receptor.
Authors: G Radhakrishna Pillai; Anand S Srivastava; Tarek I Hassanein; Dharam P Chauhan; Ewa Carrier Journal: Cancer Lett Date: 2004-05-28 Impact factor: 8.679
Authors: Bruce A Arnow; Enid M Hunkeler; Christine M Blasey; Janelle Lee; Michael J Constantino; Bruce Fireman; Helena C Kraemer; Robin Dea; Rebecca Robinson; Chris Hayward Journal: Psychosom Med Date: 2006 Mar-Apr Impact factor: 4.312