TO WHAT EXTENT DO SPINAL INTERACTIONS BETWEEN AN ALPHA-2-ADRENOCEPTORAGONIST AND A MU-OPIOID AGONIST INFLUENCE NOXIOUSLY EVOKED C-FOS EXPRESSION IN THE RAT - A PHARMACOLOGICAL STUDY

Three hours after the intraplantar injection of carrageenin (6 mg/150 mu l of saline) Fos-like immunoreactivity (Fos-LI) was observed in bot h superficial and deep laminae of the dorsal horn segments L4 and L5 o f the spinal cord. Systemic medetomidine, an alpha-2 adrenoceptor agon ist (12.5, 25 or 75 mu g/kg i.v.), dose-dependently reduced the number of superficial and deep Fos-LI neurons; 75 mu g/kg produced a 66 +/- 4% and a 90 +/- 4% reduction of superficial and deep Fos-LI neurons, r espectively, P < .0001 for both. In addition, systemic medetomidine do se-relatedly reduced the carrageenin-evoked paw and ankle edema; medet omidine 75 mu g/kg resulted in a 70 +/- 3% reduction of paw edema and in a blockade of the development of ankle edema. The effects of medeto midine were blocked by systemic atipamezole (75 mu g/kg, i.v.), which, when injected alone, had no effect on the number of Fos-LI neurons or the peripheral edema. Go-administration of a low dose of medetomidine (12.5 mu g/kg i.v.) with an ineffective dose of morphine (1.5 mg/kg i .v.) strongly decreased the number of superficial and deep Fos-LI neur ons (40 +/- 5%, P < .0001 and 62 +/- 11%, P < .0001 reduction as compa red with control group) without altering the effects of medetomidine o n the peripheral edema. Both atipamezole and a combined injection of a tipamezole and naloxone blocked the effects of medetomidine plus morph ine on both the total number of Fos-LI neurons (86 +/- 11% and 86 +/- 6% of control, respectively) and carrageenin inflammation (87 +/- 6%, P < .05 and 84 +/- 3%, P < .05 of control for the paw edema; 75 +/- 8% , P < .01 and 81 +/- 7%, P < .05 of control for the ankle edema, respe ctively). Naloxone alone blocked the effects of the co-administered ag onists on the total number of Fos-LI neurons (91 +/- 6% of the control carrageenin group) without influencing the effect on the peripheral e dema. Our results demonstrate, for the first time, that cc-administrat ion of alpha-2 adrenoceptor and mu opioid agonists substantially reduc es inflammatory evoked expression of c-Fos, one of the long-term conse quences of sustained nociceptive processing.