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

Joshua P. Johansen1, Howard L. Fields1, Barton H. Manning1
1Department of Neurology and the W. M. Keck Foundation Center for Integrative Neuroscience, University of California, San Francisco, CA 94143-0453; and Department of Neuroscience, Merck Research Laboratories, Merck and Co., Inc., West Point, PA 19486-0004

Tóm tắt

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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Tài liệu tham khảo

10.1016/S0304-3959(99)00139-6

R Melzack, K L Casey The Skin Senses, ed D Kenshalo (Thomas, Springfield, IL), pp. 423–439 (1968).

10.1016/0304-3959(75)90044-5

10.1126/science.288.5472.1769

10.1073/pnas.96.14.7705

10.1016/S0304-3959(98)00184-5

10.1007/BF00230532

10.1038/8065

10.3171/jns.1962.19.2.0089

10.1093/neurosurgery/21.CN_suppl_1.334

10.1073/pnas.96.14.7668

10.1126/science.277.5328.968

10.1152/jn.1992.68.5.1720

10.1016/0006-8993(96)00561-6

10.1016/S0306-4522(97)00662-3

10.1002/cne.902860303

10.1016/0361-9230(86)90237-6

10.1016/S0006-8993(99)01779-5

10.1016/0306-4522(87)90345-9

G J Royce Exp Brain Res 50, 157–165 (1983).

10.1016/0006-8993(84)91448-3

B H Manning, H L Fields, B K Matthies Soc Neurosci Abstr 26, 431 (2000).

G Paxinos, C Watson The Rat Brain in Stereotaxic Coordinates (Academic, New York, 1997).

N R Swerdlow, D Gilbert, G F Koob Neuromethods: Psychopharmacology, eds A A Boulton, G B Baker, A J Greenshaw (Humana, Clifton, NJ), pp. 399–446 (2000).

10.1523/JNEUROSCI.18-22-09453.1998

C V Howard, M G Reed Unbiased Stereology: Three Dimensional Measurement in Microscopy (Springer, New York, 1998).

10.1016/0306-4522(91)90151-D

10.1097/00001756-199708180-00013

10.1002/cne.901950406

10.1007/s002130050447

T S Shippenberg, R Bals-Kubik, A Herz J Pharmacol Exp Ther 265, 53–59 (1993).

10.1016/0304-3959(95)00121-2

10.1016/0304-3959(77)90130-0

10.1111/j.1460-9568.1996.tb01608.x

10.1152/jn.1997.77.6.3370

10.1046/j.1460-9568.1999.00834.x

10.1016/S0166-4328(98)00034-5

10.1016/S0304-3940(97)00310-8

10.1097/00001756-199808030-00044

10.1016/S0304-3940(00)00894-6

10.1016/0304-3940(82)90327-5

10.1053/eujp.1999.0158