The 5-HT2A receptor potassium-chloride cotransporter 2 signaling pathway in a rat incision pain model
نویسندگان
چکیده
Postoperative pain is a critical problem in clinical pain administration. Due to the unclear formation mechanism of postoperative pain, the treatment of postoperative pain is still in the symptomatic treatment stage and lacking satisfactory analgesic effect. Postoperative pain can be simulated by using a rat incision pain model. We observed changes in pain-related behavior of rats affected by the 5-hydroxytryptamine 2A receptor (5-HT2AR) agonist, TCB-2, and antagonist, ketanserin, through intrathecal delivery. The transcription and translation level of potassium-chloride cotransporter 2 (KCC2) in the spinal cord was also measured to investigate the role of the 5-HT2AR-KCC2 pathway in the mechanism of incision pain. Compared with the control group, rats in the incision pain group had decreased mechanical withdrawal threshold (MWT), with significant differences on day 1-7 after surgery, and significant decreases in thermal withdrawal latency (TWL) on days 1, 2, 3 and 6 (P<0.05). Compared with the incision + dimethyl sulfoxide (DMSO) group, MWT and TWL decreased in the incision + ketanserin group on day 1 and 2 (P<0.05). There was no significant difference detected in TWL of incision + TCB-2 group on day 1, while MWT increased significantly compared to the incision + DMSO group (P<0.05). Furthermore, the transcription and translation levels of KCC2 in the incision + ketanserin group decreased significantly in comparison to the incision + DMSO group (P<0.05), while an increase was detected in the incision + TCB-2 group (P<0.05). MWT and TWL decreased in the incision pain rats, accompanied with a decreased transcription and translation level of KCC2. Intrathecal delivery of the 5-HT2AR agonist, TCB-2, alleviated the decreased WMT and inhibited the decreased transcription and translation level of KCC2, while intrathecal delivery of the 5-HT2AR antagonist, ketanserin, aggravated the decreased WMT and transcription and translation levels of KCC2, suggesting the involement of the 5-HT2AR-KCC2 pathway in the formation mechanism of incision pain in rats.
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