Objective To explore the potential mechanism of propofol in relieving postoperative pain in rats through p38 mitogen-activated protein kinase (MAPK) signaling pathway.

Methods A postoperative neuropathic pain model was constructed by transient clamping with vascular clips, and thirty-six SD rats were randomly divided into four groups using a random number table method: control group (untreated), surgery group (receiving PELD treatment), surgery+propofol treatment group receiving PELD treatment and an intravenous injection of propofol at 1.5 mg/(kg·min) through the lateral tail vein of the rats, and surgery+propofol+p38MAPK agonist Diprovocim group receiving PELD treatment, with an intravenous injection of 1.5 mg/(kg·min) propofol and 5 nmol/L of the p38MAPK agonist Diprovocim through the lateral tail vein of the rats. After 14 d of continuous drug administration, the rats were tested for mechanical nociceptive thresholds using the Von-Frey test probe, and thermal nociceptive thresholds were detected by the Hargreaves experiment; the activation of spinal cord dorsal horn glial cells was detected by immunofluorescence assay; p38 phosphorylation (p-p38), MAPK phosphorylation(p-MAPK) and downstream interleukin-1β (IL-1β), P53, and CHOP protein expression levels were detected by immunoprotein blotting assay (Western blotting).

Results Rats in the surgery group exhibited neuropathic pain 12 hours postoperatively ollowing probe stimulation, with pain peaking on postoperative day 10 and gradually subsiding thereafter. Rats in the surgery + propofol treatment group also experienced neuropathic pain 12 hours postoperatively, but the pain intensity decreased at 24 hours, and gradually subsided by postoperative day 14. Rats in the surgery+propofol+p38MAPK agonist Diprovocim group developed neuropathic pain 12 hours postoperatively, with no significant decrease in pain threshold at 24 hours, and pain peaked on postoperative day 10 before gradually subsiding. Compared with the control group, the surgery group showed increased levels of P53 protein, p-p38 and p-MAPK in the posterior horn of the spinal cord, increased expression of downstream interleukin-1β (IL-1β) and CHOP proteins, and enhanced glial cell activation on the operated side (P < 0.05). When compared with the surgery group, the surgery+propofol treatment group exhibited decreased levels of p-p38, p-MAPK, and downstream IL-1β, P53, and CHOP protein expression, as well as reduced glial cell activation (P < 0.05).Conclusion with the surgery+propofol treatment group, the surgery+propofol+p38MAPK agonist Diprovocim group showed decreased expression levels of IL-1β, P53, and CHOP proteins and levels of p-p38, p-MAPK (P < 0.05).

Conclusion Propofol can relieve postoperative pain in rats through p38MAPK signaling pathway.