MK-801 inhibits formalin-induced cyclooxygenase-2 expression in the dorsal horn of the spinal cord in rats / 生理学报

ABSTRACT

To investigate the effect of N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 on the formalin-induced cyclooxygenase-2 (COX-2) expression in the dorsal horn of the rat spinal cord. Forty-eight male Sprague-Dawley rats were divided into 4 groups control, formalin, formalin+normal saline (NS) and formalin+MK-801 groups. Rats in formalin, formalin+NS and formalin+MK-801 groups were subcutaneously injected with 0.2 ml 5% formalin into the plantar surface of the right hind paw. NS or MK-801 solution (10 microl) was intrathecally injected under transient ether anesthesia 15 min prior to the formalin injection in the formalin+NS and formalin+MK-801 groups, respectively. Flinch reflex was measured within 1 h after the formalin injection and expression of COX-2 in the dorsal horn of the L(5) segment of the spinal cord was assayed 24 h after the formalin injection using immunohistochemistry. Formalin evoked a biphasic flinch reflex. MK-801 produced a limited effect on the flinch reflex of phase 1, but produced significant and dose-dependent suppression on the flinch reflex of phase 2. The number and immunostaining density, shown by grey degree which was inversely proportional to the immunostaining density, of immunoreactive soma in the superficial (mainly I-II) and deep (IV-VI) laminae of the L(5) spinal cord in formalin and formalin+NS groups increased significantly, in contrast to those in the control group (p<0.01). The number and immunostaining density of immunoreactive soma decreased significantly in formalin+MK-801 group, in comparison with the formalin+NS group (p<0.05). The degree of the decrease was proportional to the dosage of MK-801 used. In addition, there were some immunoreactive processes especially in the superficial laminae, which extended as a continuous band across the dorsal horn after the formalin injection. Change in immunostaining density of the processes after administration of MK-801 was similar to that in the immunoreactive soma. The results showed that intrathecal injection of MK-801 significantly inhibited the increase of COX-2 expression in the spinal dorsal horn induced by the formalin injection in a dose-dependent manner, suggesting that the activation of NMDA receptor is one of the mechanisms for the formalin-induced increase of COX-2 expression in the spinal dorsal horn.