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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., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Glycoprotein 120 (gp120) is an HIV envelope glycoprotein. Gp120 can directly stimulate the primary sensory afferent neurons and cause hyperalgesia. The P2X 3 receptor in dorsal root ganglia (DRG) is involved in the transmission of pain. In this study, we aimed to explore the role of the P2X 3 receptor in gp120-induced neuropathic pain. Our data showed that mechanical and thermal hyperalgesia in rats treated with gp120 were increased compared to those in the control group. The expression levels of the P2X 3 mRNA and protein in rats treated with gp120 were higher than those in the control group. The P2X 3 antagonist A317491 decreased mechanical hyperalgesia and thermal hyperalgesia and the up-regulated expression levels of P2X 3 mRNA and protein in rats treated with gp120. A317491 decreased ERK1/2 phosphorylation levels in the gp120-treated rat DRG. In addition, P2X 3 agonist α,β-methylene ATP (α,β-meATP)-activated currents in DRG neurons cultured with gp120 were higher than those in control neurons. The inhibitory effect of A317491 on α,βme-ATP-induced currents in DRG neurons from the gp120-treated neurons was larger than that for control neurons. Molecular docking data showed that A317491 may be acted in the gp120 protein to inhibit the gp120 initiated the P2X 3 activation, decrease the sensitizing DRG primary afferents and reduce the signal transmission of neuropathic pain in gp120-treated rats. Therefore, the inhibition of the P2X 3 receptor in rat DRG neurons relieved gp120-induced mechanical hyperalgesia., (Copyright © 2017 Elsevier Inc. All rights reserved.)