Imperatorin, a natural furanocoumarin alleviates chronic neuropathic pain by targeting GABAergic tone in an animal model of spinal cord injury.

Chronic neuropathic pain (CNP) caused by spinal cord injury (SCI) has long-term implications, that result in functional deficit. In this study, we explored imperatorin, a natural furanocoumarin isolated from the dried pulp of Aegle marmelos L. Imperatorin (10 mg/kg, i.p.) was administered to injured animals for seven consecutive days. It was discovered that imperatorin reduced the CNP by upregulating the expression of anti-inflammatory chemokines and cytokines like IL-10 and IL-12, and increasing the expression of GABA with p-value < 0.001 as compared to vehicle at DPI-28 and DPI-42. Also, GABA receptor expression was increased with p-value < 0.01 as compared to vehicle at DPI-28. Additionally, it downregulated the expression of various proinflammatory mediators like IL-6 (p-value < 0.01), CCL-2 (p-value < 0.01), IL-1β (p-value < 0.01), and CCL-3 (p-value < 0.001) as compared to vehicle at DPI-1. Furthermore, imperatorin reduced scar formation by decreasing fibrosis and gliosis post-SCI and also lessened pain behaviour, suggesting it helps reduce chronic neuropathic pain (CNP).