Osthole alleviated diabetic neuropathic pain mediated by the P2X4 receptor in dorsal root ganglia.

Highlights • Up-regulated P2X 4 in DRG SGCs companied with diabetic neuropathic pain. • Osthole decreased up-regulated P2X 4 and hyperalgesia in diabetic rats. • Osthole inhibited SGC activation in DRG of diabetic rats. • Osthole alleviate diabetic neuropathic pain by inhibiting P2X 4. Abstract Diabetes mellitus (DM) is considered the primary cause of neuropathic pain. Osthole (7-methoxy-8[3-methylpent 2-enyl]coumarin) is a component extracted from Cnidium monnieri (L.) cusson plant seeds and has anti-inflammatory and anti-oxidative properties. The aim of the present study was to investigate the effects of osthole on diabetic neuropathic pain (DNP) involving the P2X 4 receptor on satellite glial cells (SGCs) in the dorsal root ganglia (DRG) of type 2 diabetic rats. These data showed that the mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) in DM rats were lower than those in control rats. MWT and TWL in DM rats treated with osthole were higher compared with those in untreated DM rats. The expression levels of P2X 4 mRNA and protein in the DRG of DM rats were higher compared with those in the control rats, while those in DM rats treated with osthole were significantly lower compared with those in the untreated DM rats. Osthole treatment decreased the co-expression levels of P2X 4 and glial fibrillary acidic protein (GFAP) and reduced the up-regulated expression of interleukin-1 beta (IL-1β), tumour necrosis factor-α (TNF-α), brain-derived neurotrophic factor (BDNF) and phosphorylated-p38MAPK and enhanced the down-regulation of IL-10 in DM rats. Thus, osthole treatment may act on the P2X 4 receptor to alleviate the mechanical and thermal hyperalgesia in DM rats. [ABSTRACT FROM AUTHOR]