Role of P2Y1 purinergic receptors in the spinal cord in a rat model of bone cancer pain

Abstract

Objective To investigate the role of P2Y1 purinergic receptors in the spinal cord in a rat model of bone cancer pain. Methods Ninety female SD rats weighing 150-180 g were randomly divided into 5 groups （n = 18 each）： Ⅰ group sham operation; Ⅱ group bone cancer pain; Ⅲ group sham operation ＋ MRS2179 （a specific P2Y1 purinergic receptor antagonist）; Ⅳ group BCP ＋ vehicle （group NS）; Ⅴ group BCP＋ MRS2179.Bone cancer pain was induced by inoculating Walker 256 mammary gland carcinoma cells into medullary cavity of tibia. In group Ⅲ, Ⅳ, Ⅴ MRS2179 100 pmol/10 μl or NS 10 μl was injected intrathecally once a day for 3 days starting from the 7th day after operation. Mechanical pain threshold to von Frey stimuli was measured before and every other day after operation. The anirnals were sacrificed on the 9th day after operation. The L4-6 segment of the spinal cord was removed for detection of expression of P2Y1 receptor and phosphorylated extracellular signal-regulated protein kinase 1/2 （p-ERK1/2） in the spinal dorsal horn. Results P2Y1 receptors and p-ERK1/2 coexisted in spinal dorsal horn. Inoculation of cancer cells into tibia significantly decreased mechanical pain threshold at postoperative day 6-18 and increased the expression of P2Y1 receptor and p-ERK1/2 on the 9th day after operation in group Ⅱ and Ⅳ as compared with group Ⅰ . Intrathecal MRS 2179 significantly increased pain threshold and decreased expression of P2Y1 receptor and p-ERK1/2 in group Ⅴ compared with group Ⅱ and Ⅳ. Conclusion P2Y1 receptors in the spinal cord are involved in the development of bone cancer pain, which may be related to the activation of ERK1/2. Key words: Receptors,purinergic P2; Bone neoplasms; Pain; Spinal cord