Effect of emodin on neuropathic pain transmission mediated by P2X2/3 receptor of primary sensory neurons

Neuropathic pain is the most difficult type of pain to cure. The P2X2/3 receptors play a crucial role in facilitating the transmission of pain at neuropathic pain states. Emodin is a natural anthraquinone in rhubarb. The present research investigated the effects of emodin on the pain transmission in neuropathic pain states that was mediated by P2X2/3 receptor in primary sensory neurons. Chronic constriction injury (CCI) model was used as neuropathic pain model. Emodin was dissolved in 0.5% sodium carboxymethyl cellulose (CMC) as vehicle. Sprague–Dawley male rats had been randomly divided into Sham + vehicle group, CCI + emodin group, and CCI + vehicle group. Mechanical withdrawal threshold and thermal withdrawal latency were measured. P2X2/3 expression in L4/L5 dorsal root ganglion (DRG) was detected by immunohistochemistry, in situ hybridization (ISH) and RT-PCR. The mechanical withdrawal threshold and thermal withdrawal latency in CCI + vehicle group were lower than those in Sham + vehicle group and CCI + emodin group (p < 0.05), while P2X2 and P2X3 receptor expression of L4/L5 DRG in CCI + vehicle group was higher than those in the other two groups (p < 0.05). The co-local staining of P2X2 and P2X3 in the DRG of CCI group appeared to be more intense than that in the DRG of the other two groups with double-label fluorescence immunohistochemistry. The results showed that the application of emodin alleviated the hyperalgesia of CCI rats and significantly decreased the P2X2/3 expression of L4/L5 DRG in CCI + emodin group compared with that in CCI + vehicle group (p < 0.05). The data of ISH and RT-PCR in P2X2 and P2X3 mRNA expression suggest that the pharmacologic mechanism of emodin is involved in the nucleic acid level. The results showed that emodin can inhibit the transmission of neuropathic pain mediated by P2X2/3 receptor of primary sensory neurons to alleviate chronic neuropathic pain.

Research highlights
► Emodin is an active anthraquinone constituent of rhubarb extract.
► The application of emodin decreased the hyperalgesia of CCI rats and the P2X2/3 expression of L4/L5 DRG in CCI rats.
► Emodin can alleviate chronic neuropathic pain mediated by P2X2/3 receptor of primary sensory neurons.