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Proc Natl Acad Sci U S A. 2001 Jul 3;98(14):8077-82. Epub 2001 Jun 19.

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

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Department of Neurology and the W. M. Keck Foundation Center for Integrative Neuroscience, University of California, San Francisco, CA 94143-0453, USA.


Numerous human and animal studies indirectly implicate neurons in the anterior cingulate cortex (ACC) in the encoding of the affective consequences of nociceptor stimulation. No causal evidence, however, has been put forth linking the ACC specifically to this function. Using a rodent pain assay that combines the hind-paw formalin model with the place-conditioning paradigm, we measured a learned behavior that directly reflects the affective component of pain in the rat (formalin-induced conditioned place avoidance) concomitantly with "acute" formalin-induced nociceptive behaviors (paw lifting, licking, and flinching) that reflect the intensity and localization of the nociceptive stimulus. Destruction of neurons originating from the rostral, but not caudal, ACC reduced formalin-induced conditioned place avoidance without reducing acute pain-related behaviors. These results provide evidence indicating that neurons in the ACC are necessary for the "aversiveness" of nociceptor stimulation.

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