Background and Aims Gastrodin (a main bioactive component of herbal plant, Gastrodia elata) has been shown to have beneficial effects in preclinical models of CNS disorders and clinical trial for migraine. Inflammasome is a multimeric protein complex having a core of pattern recognition receptor and has been implicated in the development of neuroinflammatory diseases. Gastrodin has shown to modulate the activation of NLRP3 (NOD-like receptor protein 3) inflammasome. This study investigated examined the effects of gastrodin on neuropathic pain and the associated changes of activation of NLRP3 inflammasome at spinal level.

Methods Intrathecal catheter implantation and spinal nerve ligation (SNL) were used for drug administration and pain model in male Sprague-Dawley rats with approval of Ethical Committee (CNUHIACUC-21056). Anti-allodynic effect of gastrodin or MCC950 (NLRP3 inflammasome inhibitor) was measured by von Frey test. Changes of NLRP3, ASC, caspase-1 and IL-1β and cellular expression were examined in the spinal cord and dorsal root ganglion.

Results Intrathecal injection of gastrodin significantly attenuated SNL-induced mechanical allodynia. MCC950 also showed anti-allodynic effect, but only about 50% of the maximum effect of gastrodin. Protein and mRNA levels of NLRP3 components and IL-1β were upregulated in SNL animals compared to sham animals, which was significantly reduced by intrathecal treatment of gastrodin. NLRP3 inflammasome were expressed mostly in the neurons, and its fluorescent intensity was also reduced by intrathecal gastrodin.

Conclusions NLRP3 inflammasome was expressed mainly in the neurons at spinal level and greatly increased in SNL. Intrathecal gastrodin has anti-allodynic effect in SNL model partly through suppressing NLRP3 inflammasome and IL-1β.