INTRAPLANTAR MORPHINE DEPRESSES SPINAL C-FOS EXPRESSION INDUCED BY CARRAGEENAN INFLAMMATION BUT NOT BY NOXIOUS HEAT

1 We have studied the effects of intraplantar administration of the sa me doses of morphine on intraplantar carrageenin (6 mg 150 mu l(-1) of saline) and noxious heat (52 degrees C for 15 s) induced spinal c-Fos expression and inflammation. 2 Intraplantar carrageenin, in awake rat s, induced numerous Fos-like immunoreactive (Fos-LI) neurones in the d orsal horn of L4-L5 lumbar segments of the spinal cord and extensive p eripheral oedema. At 1 h 30 min, Fos-LI neurones were preferentially l ocated in the superficial laminae (74+/-2%) whereas at 3 h, Fos-LI neu rones were observed both in the superficial (45+/-2%) and deep (37+/-1 %) laminae of the spinal dorsal horn. 3 Intraplantar morphine dose-dep endently reduced c-Fos expression induced 1 h 30 min after carrageenin (r=0.605, P<0.02), these effects were completely blocked by intraplan tar methiodide naloxone (20 pg) (121+/-22% of control carrageenin expr ession). The systemic injection of the highest dose of intraplantar mo rphine (50 mu g) had no significant effect on the number of Fos-LI neu rones (88+/-9% of control carrageenin expression). None of the drugs i nfluenced unilateral peripheral oedema observed 1 h 30 min after carra geenin. 4 In the second series of experiments, intraplantar morphine d ose-dependently reduced the number of superficial and deep Fos-LI neur ones induced 3 h after carrageenin (r=0.794, P<0.0004 and r=0.698, P<0 .004, respectively). Furthermore, the effects of the highest dose of i ntraplantar morphine were completely blocked by co-administration of i ntraplantar methiodide naloxone (20 mu g). 5 In addition, intraplantar morphine dose-dependently reduced the ankle (r=0.747, P<0.002) and pa w (r=0.682, P<0.005) oedema observed 3 h after carrageenin, with the e ffect of the highest dose of intraplantar morphine being completely bl ocked by co-administration of methiodide naloxone (98+/-4% and 102+/-8 % of control paw and ankle oedema, respectively). 6 Brief noxious heat stimulation, in urethane anaesthetized rats, induced, 2 h after the s timulation, numerous Fos-LI neurones in the dorsal horn of L3-L4 lumba r segments of the spinal cord but no detectable peripheral oedema. Fos -LI neurones were preferentially located in superficial laminae (94+/- 2%) of the spinal dorsal horn. None of the drugs influenced the noxiou s heat induced c-Fos expression. 7 Such results illustrate that periph eral effects of morphine preferentially occur during inflammatory stat es and outline the interest of extending clinical investigations of th e possible use of local injection of morphine in various inflammatory pain states.