The affective component of pain in rodents: Direct evidence for a contribution of the anterior cingulate cortex

Numerous human and animal studies indirectly implicate neurons in the anter ior cingulate cortex (ACC) in the encoding of the affective consequences of nociceptor stimulation. No causal evidence, however, has been put forth li nking the ACC specifically to this function. Using a rodent pain assay that combines the hindpaw formalin model with the place-conditioning paradigm, we measured a learned behavior that directly reflects the affective compone nt of pain in the rat (formalin-induced conditioned place avoidance) concom itantly with "acute" formalin-induced nociceptive behaviors (paw lifting, l icking, and flinching) that reflect the intensity and localization of the n ociceptive stimulus. Destruction of neurons originating from the rostral, b ut not caudal, ACC reduced formalin-induced conditioned place avoidance wit hout reducing acute pain-related behaviors. These results provide evidence indicating that neurons in the ACC are necessary for the "aversiveness" of nociceptor stimulation.