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

The unilateral sciatic nerve chronic constriction injury (CCI) model of Ben nett and Xie [G.J. Bennett, Y.-K. Xie, A peripheral neuropathy in rat that produces disorders of pain sensation like those seen in man, Pain, 33 (1988 ) 87-108] shows features of a neuropathic pain state. We examined mechanica l hyperalgesia and Fos protein staining in the lumbar spinal cord 1, 7, 14 and 28 days after unilateral CCI to the sciatic nerve or sham operation, in addition, we examined the effect of the NMDA antagonist MK-801 (0.3 mg/kg s.c. administered 30 min prior to and 6 h following operation) on Fos expre ssion and hyperalgesia at 28 days. CCI animals were hyperalgesic compared t o the sham operated animals at 14 and 28 days post injury. MK-801 reduced h yperalgesia by 68% in CCI animals on day 28 (p = 0.0001). In the spinal cor d, Fos positive cells were present bilaterally in deeper laminae in both sh am and CCI animals at all time points examined. Relatively few Fos positive cells were present in laminae 1-2 at any time point examined. At days 1 an d 7, there were increased numbers of Fos positive cells ipsilaterally in th e deeper laminae of the spinal cord in CCI animals compared to sham animals , but by 14 and 28 days Fos counts were similar in sham and CCI despite the obvious behavioural differences between the two groups. Fos counts ipsilat eral to the injury in laminae 3-10 correlated with hyperalgesia scores in t he CCI but not sham animals. Analysis at the 28-day time point showed that MK-801 differentially affected Fos expression: MK-801 significantly reduced the Fos count bilaterally in laminae 3-10 in the CCI but not in the sham g roup animals. These results indicate that Fos expression is initiated by di fferent peripheral and central mechanisms following nerve injury or sham op eration. (C) 1999 Elsevier Science B.V. All rights reserved.