The Antinociceptive Potential of Camellia japonica Leaf Extract, (−)-Epicatechin, and Rutin against Chronic Constriction Injury-Induced Neuropathic Pain in Rats

Neuropathic pain is caused by a lesion or disease of the somatosensory nervous system. Currently, prescribed treatments are still unsatisfactory or have limited effectiveness. Camellia japonica leaves are known to have antioxidant and anti-inflammatory properties.; however, their antinociceptive efficacy has not yet been explored. We examined the antinociceptive efficacy and underlying mechanism of C. japonica leaf extract (CJE) in chronic constriction injury (CCI)-induced neuropathic pain models. To test the antinociceptive activity of CJE, three types of allodynia were evaluated: punctate allodynia using von Frey filaments, dynamic allodynia using a paintbrush and cotton swab, and cold allodynia using a cold plate test. CCI rats developed neuropathic pain representing increases in the three types of allodynia and spontaneous pain. In addition, CCI rats showed high phosphorylation levels of mitogen-activated protein kinases (MAPKs), transcription factors, and nociceptive mediators in dorsal root ganglion (DRG). The ionized calcium-binding adapter molecule 1 levels and neuroinflammation also increased following CCI surgery in the spinal cord. CJE and its active components have potential antinociceptive effects against CCI-induced neuropathic pain that might be mediated by MAPK activation in the DRG and microglial activation in the spinal cord. These findings suggest that CJE, (−)-epicatechin, and rutin could be novel candidates for neuropathic pain management.