Periplaneta americana Powder Alleviates Neuropathic Pain and is Associated with Gut Microbiota Changes in Rats

Dan Luo,1,2 Shuaiying Jia,3 Wenting He,1,2 Zhidong Fan,1,2 Wenqin Yin3 1The Department of Clinical Medicine, Health Science Center of Dali University, Dali, Dali Bai Autonomous Prefecture, Yunnan Province, People’s Republic of China; 2Department of Anesthesiology, the First Affiliated Hospital of Dali University, Dali, Dali Bai Autonomous Prefecture, Yunnan Province, People’s Republic of China; 3Department of Anesthesiology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, People’s Republic of ChinaCorrespondence: Zhidong Fan, Department of Anesthesiology, the First Affiliated Hospital of Dali University, Dali, Dali Bai Autonomous Prefecture, Yunnan Province, People’s Republic of China, Email [email protected] Wenqin Yin, Department of Anesthesiology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan Province, People’s Republic of China, Email [email protected]: This study aims to evaluate the therapeutic potential of Periplaneta americana powder (PAP) in alleviating neuropathic pain in a rat model of sciatic nerve injury induced by chronic constriction injury (CCI), and to systematically analyze its effects on the composition and structure of the gut microbiota during the intervention process, with the goal of elucidating the mechanisms underlying the analgesic effects of PAP.Methods: A rat model of CCI was established (n = 12 per group), and PAP was administered for intervention. The analgesic effects were evaluated using mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL). Pathological changes in the spinal cord and colon tissues were examined via hematoxylin-eosin (HE) staining, and the expression of the astrocyte marker glial fibrillary acidic protein (GFAP) in the spinal cord was detected by immunohistochemistry. The expression levels of pro-inflammatory cytokines TNF-α and IL-1β in spinal cord tissues were measured using enzyme-linked immunosorbent assay (ELISA). Fecal samples were collected at the endpoint of treatment for metagenomic sequencing and analysis.Results: After PAP treatment, behavioral tests in CCI rats showed a significant increase in MWT and TWL (P < 0.05). Histological analysis revealed marked alleviation of spinal cord and colon tissue damage as well as reduced inflammatory cell infiltration (P < 0.05). Immunohistochemistry further demonstrated a significant decrease in GFAP expression in the spinal cord (P < 0.05). ELISA results showed that the expression levels of TNF-α and IL-1β in spinal cord tissues were significantly decreased (P < 0.05).Metagenomic analysis indicated that PAP reshaped the gut microbiota structure, increased the abundance of SCFA-producing bacteria, and was associated with the butyrate metabolism pathway.Conclusion: This study indicates that PAP can significantly alleviate neuropathic pain in a rat model of sciatic nerve chronic constriction injury (CCI) and suppress the central inflammatory response.Notably, this effect is accompanied by changes in the gut microbiota, particularly characterized by a significant alteration in the abundance of short-chain fatty acid-producing bacteria. These results suggest that PAP not only possesses substantial analgesic effects but may also mediate the intervention of CCI-induced neuropathic pain by regulating the structure of the gut microbiota.Keywords: Periplaneta americana, gut microbiota, neuropathic pain, SCFA, fecal metagenomic sequencing