Changes in expression of purinergic P2X4 receptor in spinal cord dorsal horn and dorsal root ganglion in a rat model of acute morphine tolerance or inflammatory pain

Abstract

Objective To evaluate the changes in the expression of purinergic P2X4 receptor (P2X4R) in spinal cord dorsal horn and dorsal root ganglion in a rat model of acute morphine tolerance or inflammatory pain.Methods Thirty male SD rats were randomly divided into 3 groups:normal saline group (group NS,n =5);acute morphine tolerance group (group M,n =5) and inflammatory pain group (group F,n =20).Inflammatory pain was induced by subcutaneous injection of 4％ formalin 50 μl into the plantar surface of left hindpaw in group F.The animals received intrathecal morphine 10 μg ( 10 μl) once every 2 h for 6 times (T1-6) in group M,while the equal volume of normal saline was given instead in group NS.The rats were then sacrificed 2 h after the last time administration.Paw withdrawal latency (PWL) to a thermal nociceptive stimulus was measured at T1-6 in groups M and NS,or on day 4,7,10 and 14 after establishing the model of inflammatory pain in group F,The rats were sacrificed after measurement of PWL and spinal cord dorsal horn and dorsal root ganglion were removed to detect the expression of P2X4 R by immuno-histochemisty.Results Compared with the baseline value,PWL was significantly decreased on day 4-14 after intlammatory pain in group F,and PWL was significantly increased at T1-5,while no significant change was found at T6 in group M ( P ＞ 0.05).Compared with group NS,the expression of P2X4 R was up-regulated in group M,and the expression of P2X4 R was up-regulated on day 4 after inflammatory pain,peaked on day 7 after inflammatory pain,and then was down-regulated gradually on day 10 and 14 after inflammatory pain in group F ( P ＜ 0.01).Conclusion The expression of purinergic P2Y4 R is up-regulated in spinal cord dorsal horn and dorsal root ganglion in rats with acute morphine tolerance or inflammatory pain,and the change may be related to the development of acute morphine tolerance or inflammatory pain. Key words: Receptors,purinergic P2; Morphine; Drug tolerance; Inflammation