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

Abstract

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).