Anti-inflammatory and analgesic effects of marine-derived antimicrobial peptide tilapia piscidin 3(TP3) in alleviating chronic constriction injury-induced neuropathic pain in rats

Abstract

Neuropathic pain has multiple etiologies, and many patients remain inadequately treated. The cyclic adenosine monophosphate (cAMP) signaling pathway plays a critical role in inflammatory responses, particularly through the upregulation of proinflammatory cytokines. This study aimed to investigate the anti-inflammatory and analgesic properties of the marine-derived antimicrobial peptide Tilapia Piscidin 3 (TP3), using a chronic constriction injury (CCI) model to simulate neuropathic pain. In vitro assays showed that TP3 exerted a dose-dependent inhibitory effect on lipopolysaccharide-induced proinflammatory cytokine expression in mouse BV-2 microglia and RAW 264.7 macrophages. Nociceptive behavioral tests revealed that intrathecal (IT) administration of TP3 alleviated CCI-induced mechanical allodynia and thermal hyperalgesia. Immunofluorescence analysis showed that IT TP3 significantly increased phosphodiesterase 4D (PDE4D) levels and decreased the expression of cAMP, brain-derived neurotrophic factor (BDNF), and tumor necrosis factor-α in astrocytes within the dorsal horn of the spinal cord in CCI rats. The antinociceptive effects of TP3 were abolished by the PDE4D inhibitor rolipram, highlighting the role of PDE4D-mediated modulation of the cAMP pathway in producing these effects. These findings suggest that TP3 may be a promising therapeutic agent for treating neuropathic pain by exerting anti-inflammatory and analgesic effects through regulation of the cAMP pathway.