Dynamics of Spinal Inotropic Glutamate Receptors During the Development of Prolonged Postoperative Pain in the Rat.

Abstract

Surgery can cause pain that lasts for weeks to months. Postoperative pain involves an early induction phase (hours to l days), and a longer maintenance phase. Experimental post-operative pain can be lowered by pre-operative spinal glutamate receptor antagonists as well as inhibitors of certain mitogen activated protein kinases (MAPKs). Here a model of postoperative pain in the rat, leading to 4 weeks of secondary mechanical allodynia-hyperalgesia, was used to examine changes in spinal inotropic glutamate receptors and MAPKs. Western blots show that GluR1subunits of AMPA receptors undergo rapid increases in phosphorylation at 4h post-op (2.3x naive), before tactile hyperalgesia is detectable, change to 1.6x naive at 2d post-op, when hyperalgesia is clearly present, and fall to sub-baseline levels (0.1x naive) at 14d, when hyperalgesia is maximum. The NR1 subunit of NMDA receptors are 1.7x, 1.8x, and 1.1x the level of naive at 4h, 2d and 14d, respectively, whilst the phosphorylated form occurs at 1.7x, 0.9x and 0.5x of naive at these times. NR2B subunit amounts follow a similar trend; 1.6x, 1.7x and 0.8x. Phosphorylation of the MAPK JNK was elevated to 1.45x, 1.35x and fell to 0.8x of naive at 4h, 2d and 14d postoperative, whilst pERK 1/2 phosphorylation remained unchanged. These results suggest that increases in total NMDA subunits and in phosphorylated NMDA and AMPA receptors, paralleled by elevated P~JNK, contribute to the induction phase of persistent post-operative pain, but are not involved in its maintenance.