Differential expression of spinal γ-aminobutyric acid and opioid receptors modulates the analgesic effects of intrathecal curcumin on postoperative/inflammatory pain in rats

摘要

Background: Curcumin is traditionally used as an herbal medicine. We explored the efficacy of intrathecal curcumin in relieving both postoperative and inflammatory pain and elucidated the mechanisms of action of curcumin interacting with γ-aminobutyric acid (GABA) and opioid receptors at the spinal level. Methods: Experimental pain was induced in male Sprague-Dawley rats via paw incision or injection of intraplantar carrageenan. After examination of the effects of intrathecal curcumin on the pain, GABA and opioid receptor antagonists were intrathecally administered to explore the involvement of GABA or opioid receptors on the effect of curcumin. Additionally, the expression levels of the GABA and opioid receptors were assessed. Results: Intrathecal curcumin reduced the withdrawal threshold of both incisional surgery- and carrageenan injection-induced nociception. Intrathecal GABA and opioid receptor antagonists reversed the curcumin-mediated antinociception. Incisional surgery decreased the levels of the GABA receptors mRNA, but little changed the levels of the opioid receptors mRNA. Carrageenan injection increased the levels of the opioid receptors mRNA, but not the GABA receptors mRNA levels. Intrathecal curcumin increased or decreased the levels of GABA receptors mRNA and opioid receptors mRNA in the spinal cords of incised or carrageenan-injected rats, respectively. Conclusions: Intrathecal curcumin was effective to postoperative and inflammatory pain and such antinociception of curcumin was antagonized by both GABA and opioid receptor antagonists. Also, intrathecal curcumin altered the levels of GABA and opioid receptors. Thus, spinal GABA and opioid receptors may, respectively, be directly or indirectly involved when curcumin alleviates postoperative and inflammatory pain.