Curcumin suppresses NLRP3 inflammasome activation by inducing autophagy to alleviate neuropathic pain in rats.

BACKGROUND

Neuropathic pain profoundly affects the quality of life of patients and requires considerable medical resources. Extensive evidence indicates that neuroinflammation within the spinal cord plays a critical role in modulating neuropathic pain. Curcumin, renowned for its anti-inflammatory properties, has shown potential in alleviating neuropathic pain. However, the mechanisms underlying its effectiveness remains elusive. The aim of this study is to investigate whether curcumin mitigates neuropathic pain by suppressing NLRP3 inflammasome activation through the induction of autophagy.

METHODS AND RESULTS

We induced neuropathic pain in male and female rats via chronic constriction injury (CCI) of the sciatic nerve. Following CCI, the rats were administered curcumin or the autophagy inhibitor 3-methyladenine (3-MA). Mechanical allodynia, thermal hyperalgesia, and cold allodynia were used to assess pain behaviour. The affective component of neuropathic pain was assessed using the conditioned place preference (CPP) test. The levels of autophagy-related proteins (LC3I, LC3II, and p62), NLRP3 inflammasome components (NLRP3, ASC, and caspase-1), and proinflammatory mediators (IL-1β and IL-18) in the spinal cord were detected using western blotting. Immunofluorescence was utilized to assess the expression and cellular localization of p62 and NLRP3. Our results revealed that intraperitoneal injections of curcumin significantly alleviated CCI-induced neuropathic pain and associated aversive behaviours, upregulated the expression of autophagy-related proteins LC3-I and LC3-II, and concurrently downregulated p62 expression in the spinal cord. Additionally, curcumin significantly inhibited CCI-induced NLRP3 inflammasome activation (NLRP3, ASC, and caspase-1) and the expression of the proinflammatory mediators IL-1β and IL-18. However, these effects were blocked following treatment with the autophagy inhibitor 3-MA.

CONCLUSION

Our findings demonstrate that curcumin can attenuate neuropathic pain by inducing autophagy to inhibit NLRP3 inflammasome activation, thereby providing a new therapeutic target for neuropathic pain.