FORMALIN-EVOKED FOS EXPRESSION IN SPINAL-CORD IS ENHANCED IN MORPHINE-TOLERANT RATS

It has been hypothesized that tolerance to the analgesic effects of mo rphine results from the development of a compensatory response in neur ons that express the opioid receptor or in neural circuits in which th ose neurons participate. The compensatory response establishes a sensi tized state in these neurons, To determine if administration of a noxi ous stimulus can unmask a sensitization of dorsal horn neurons in morp hine-pelleted rats, we injected morphine-tolerant and control rats wit h formalin into the plantar surface of the hindpaw, counted the number of flinches for 2 h and then processed the lumbar cord for Fos immuno cytochemistry. Although there was no significant difference in flinchi ng behavior between the morphine-tolerant and control groups, we recor ded significantly increased total Fos-like immunoreactivity at the L4/ 5 and L2 segments both ipsilateral and contralateral to the site of fo rmalin injection in the morphine-tolerant rats compared to the control rats. These results suggest that lumbar spinal cord neurons are sensi tized during the development of tolerance, that the sensitization can be unmasked by the administration of a noxious stimulus and that it is manifested as increased expression of the Fos protein in the lumbar c ord. (C) 1997 Elsevier Science B.V.