Neurocircuitry of conditioned inhibition of analgesia: effects of amygdala, dorsal raphe, ventral medullary, and spinal cord lesions on antianalgesia in the rat.

Pain inhibition (analgesia) is produced by learned danger signals and inhibited by learned safety signals (antianalgesia). Conditioned analgesia is mediated by brain-to-spinal pathways releasing spinal endogenous opiates. Spinal morphine mimics learned danger signals in producing analgesia, which is inhibited by antianalgesia. The circuitry mediating antianalgesia is unknown. These experiments demonstrate that raphe dorsalis, raphe magnus, and spinal dorsolateral funiculus lesions abolish antianalgesia. Other lesions had no effect on antianalgesia. More important, lesions that blocked development of conditioned analgesia did not block development of antianalgesia. Thus, neural circuitries mediating analgesia and antianalgesia were found to be distinct, and conditioned inhibition of analgesia was found to act by inhibiting the most distal part of the conditioned analgesia circuit, namely, the spinal cord.