Effect of post-injury NMDA antagonist treatment on long-term Fos expression and hyperalgesia in a model of chronic neuropathic pain

Chronic constriction injury (CCI) of the sciatic nerve results in persisten t mechanical hyperalgesia together with Fos protein expression in the lumba r spinal cord. We have examined the relationship between mechanical hyperal gesia and Fos expression within the lumbar spinal cord on days 14, 35 and 5 5 after either CCI or sham operation. To determine the role of NMDA recepto r mechanisms in the maintenance of hyperalgesia and Fos expression, the NMD A antagonist MK-801 (0.3 mg kg(-1) s.c.) was administered daily on days 28 to 34 after operation. CCI animals developed unilateral hind limb hyperalge sia that persisted unchanged from days 14 to 55 of the study. MK-801 treatm ent reduced hyperalgesia by 57% (p = 0.02) on day 35 in CCI animals but did influence hyperalgesia at day 55. In the spinal cord, Fos positive cells w ere present bilaterally throughout laminae 3-10 at all time points examined in both CCI and sham group animals. Fos counts ipsilateral to the side of injury in laminae 3-10 correlated significantly with hyperalgesia scores in the CCI but not sham animals. MK-801 treatment resulted in a suppression o f Fos expression in ipsilateral laminae 3-4 (p = 0.0017) and laminae 5-10 ( p = 0.0026) of CCI animals on day 35. Fos expression in sham group animals was not inhibited by MK-801 treatment at day 35. These results indicate tha t Fos expression is maintained by differing mechanisms following nerve inju ry or sham operation. The functional consequences of Fos expression followi ng nerve injury and sham operation are discussed. (C) 1999 Elsevier Science B.V. All rights reserved.