Effect of tetramethylpyrazine on DRG neuron P2X3 receptor involved in transmitting pain after burn

A burn is a severe injury, and the resulting pain can be very significant. Currently, opioids are the primary method of pain management, but these drugs have side effects; thus, it is of prime focus to research the mechanisms of pain formation and analgesic drugs.

Objective

To investigate the effects of tetramethylpyrazine (TMP) on burn pain mediated by the P2X3 receptor.

Methods

First-degree and superficial second-degree burn models were used. The mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were measured, and P2X3 receptor expression on nerve terminals in burn-injured skin were detected by immunohistochemistry. The effects of TMP on the P2X receptor agonist-activated currents in freshly isolated burn-injured rat dorsal root ganglion (DRG) neurons were studied by whole-cell patch-clamp technique.

Main Results

One hour following the procedure, MWT and TWL in first and second-degree paw-burns with normal saline (NS) treatment were lower than those in the unburned control group and lasted for 24 or 96h, respectively (p<0.01). After 24h, MWT and TWL in the first-degree paw-burn with TMP treatment were significantly increased as compared with NS treatment; no difference was found when compared to the unburned control group. MWT and TWL in the second-degree paw-burn in the TMP treatment group were significantly increased at 48h compared to NS treatment. No difference was found with the values for the unburned control group after 72h. On day 3 after the burn, P2X3-receptor expression in the nerve terminal in the burn-injured skin of the first- and second-degree dorsal burns in the NS treatment group was higher than those in other groups (p<0.05). After treatment with TMP, P2X3-receptor expression of the nerve terminal in the first- and second-degree dorsal burns of the TMP treatment group was significantly decreased. ATP-activated currents (IATP) on the DRG neurons of the second-degree dorsal burn in the NS treatment group were markedly higher than those in the second-degree dorsal burns in the TMP treatment group and the unburned control group (p<0.05); there were no significant differences between the second-degree dorsal burn in the TMP treatment group and the unburned control group (p>0.05).

Conclusion

TMP alleviates nociceptive transmission of burn-injury pain mediated by the P2X3 receptor.