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.


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 96 h, respectively (p<0.01). After 24 h, 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 48 h compared to NS treatment. No difference was found with the values for the unburned control group after 72 h. 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).


CONCLUSIONS
TMP alleviates nociceptive transmission of burn-injury pain mediated by the P2X3 receptor.
Gao
Yun
Y
Department of Physiology, Basic Medical College of Nanchang University, Nanchang, Jiangxi 330006, PR China.
Xu
Changshui
C
Yu
Kehua
K
Li
Guilin
G
Wan
Fan
F
Liu
Shuangmei
S
Lin
Jiari
J
Liu
Han
H
Zhang
Jun
J
Li
Xin
X
Liang
Shangdong
S
D018712:Analgesics, Non-Narcotic / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology* / Q000627:therapeutic use; D002056:Burns / Q000150:complications* / Q000378:metabolism; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005727:Ganglia, Spinal / Q000187:drug effects* / Q000378:metabolism; D006930:Hyperalgesia / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D008297:Male; D017288:Pain Threshold / Q000187:drug effects; D018408:Patch-Clamp Techniques; D011719:Pyrazines / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D018048:Receptors, Purinergic P2 / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D058477:Receptors, Purinergic P2X3; D012867:Skin / Q000294:innervation
D018712:Analgesics, Non-Narcotic; D000894:Anti-Inflammatory Agents, Non-Steroidal; C546410:P2rx3 protein, rat; D011719:Pyrazines; D018048:Receptors, Purinergic P2; D058477:Receptors, Purinergic P2X3; C017953:tetramethylpyrazine