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Cancer pain is a well-known serious complication in metastatic or terminal cancer patients. Current pain management remains unsatisfactory. The activation of spinal and supraspinal P2X7 receptors plays a crucial role in the induction and maintenance mechanisms of various kinds of acute or chronic pain. The midbrain periaqueductal gray (PAG) is a vital supraspinal site of the endogenous descending pain-modulating system. Tramadol is a synthetic, centrally acting analgesic agent that exhibits considerable efficacy in clinically relieving pain. The purpose of this study was to determine whether the activation of P2X7 receptor in the ventrolateral region of the PAG (vlPAG) participates in the analgesic mechanisms of tramadol on bone cancer pain (BCP) in rats. The BCP rat model was established by intratibial cell inoculation of SHZ-88 mammary gland carcinoma cells. The analgesic effects of different doses of tramadol (10, 20, and 40 mg/kg ) were assessed by measuring the mechanical withdrawal threshold and thermal withdrawal latency values in rats by using an electronic von Frey anesthesiometer and radiant heat stimulation, respectively. Alterations in the number of P2X7 receptor-positive cells and P2X7 protein levels in vlPAG were separately detected by using immunohistochemistry and Western blot assay. The effect of intra-vlPAG injection of A-740003 (100 nmol), a selective competitive P2X7 receptor antagonist, on the analgesic effect of tramadol was also observed. The expression of P2X7 receptor in the vlPAG on BCP rats was mildly elevated, and the tramadol (10, 20, and 40 mg/kg) dose-dependently relieved pain-related behaviors in BCP rats and further upregulated the expression of P2X7 receptor in the vlPAG. The intra-vlPAG injection of A-740003 pretreatment partly but significantly antagonized the analgesic effect of tramadol on BCP rats. The injection of tramadol can dose-dependently elicit analgesic effect on BCP rats by promoting the expression of the P2X7 receptor in vlPAG.

Activation of the P2X7receptor in midbrain periaqueductal gray participates in the analgesic effect of tramadol in bone cancer pain rats

Activation of the P2X₇receptor in midbrain periaqueductal gray participates in the analgesic effect of tramadol in bone cancer pain rats