Supraspinal influence on hindlimb withdrawal thresholds and mustard oil-induced secondary allodynia in rats

We examined the role of supraspinal structures in secondary allodynia induced by mustard oil in awake rats. To produce allodynia (=unpleasent sensation evoked by innocuous stimuli), mustard oil (50%) was applied for 2 min to the skin of the ankle of one hindlimb. Mechanical hypersensitivity of the skin was tested by determining the hindlimb withdrawal threshold to a series of monofilaments applied to the glabrous foot pad (=distal to the mustard oil-treated ankle). In intact rats, mustard oil produced a secondary allodynia in the mustard oil-treated hindlimb as indicated by a decreased withdrawal threshold to mechanical test stimuli applied to the glabrous skin (=outside the mustard oil-treated ankle), whereas the withdrawal threshold in the contralateral (=control) hindlimb was not changed. Following spinalization, mustard oil treatment produced no secondary allodynia, but the interpretation of this finding was complicated by a concomitant bilateral elevation of hindlimb withdrawal thresholds to mechanical skin stimulation. However, the spinalized rats had shorter tail-flick latencies to radiant heat than intact rats. Administration of an opioid antagonist, naloxone (1 mg/kg, SC), had no effect on withdrawal thresholds in spinalized animals. Importantly, microinjection of lidocaine (4%) into the nucleus raphe magnus in rats with an intact spinal cord had a selective antiallodynic effect when the injection volume was 1.0 microl but not when it was 0.5 microl. Lidocaine (4%, 0.5 microl) in the lateral reticular nucleus of the medulla also attenuated the spinal hypersensitivity, however, concomitantly with motor side effects, due to which this finding maybe artificial. It is concluded that brain stem spinal pathways, originating adjacent to but not within the raphe magnus, contribute to the behavioral expression of secondary allodynia induced by neurogenic inflammation of the skin. Furthermore, there is a differential tonic control of various spinal reflexes by the brain stem as indicated by the dissociative effects of spinalization on mechanically induced hindlimb withdrawal vs. heat-induced tail-flick reflex.