Distinct roles of the anterior cingulate cortex in spinal and supraspinal bee venom-induced pain behaviors

A wide variety of human and animal experiments suggest that the anterior cingulate cortex (ACC) is one of the key brain substrates subserving higher order processing of noxious information. However, no sufficient data are now available regarding the mediation by ACC of different levels of pain processing as well as its potential descending modulation of spinal nociception. Using the well-developed rat bee venom (BV) model, the present study evaluated the effect of lesions of bilateral ACC on two levels of spontaneous nociceptive behaviors (spinally-processed persistent paw flinching reflex and supraspinally-processed paw lifting/licking) and heat or mechanical hypersensitivity under the inflammatory pain state. In contrast to the sham lesion group (saline microinjection into the ACC), bilateral complete ACC chemical lesions (kainic acid microinjection into the ACC) significantly decreased the BV-induced paw lifting and licking behavior (less time spent by the animal in paw lifting/licking) but produced no influence upon spinally-processed spontaneous paw flinching reflex (no change in number of paw flinches following subcutaneous BV injection). Moreover, the bilateral ACC lesions relieved the BV-evoked primary thermal or mechanical hypersensitivity compared with the sham control group. However, incomplete lesions of bilateral ACC failed to affect the abovementioned pain-related behaviors. No effects were seen on basal pain sensitivity in either group of rats. Motor coordination, as measured by Rota-Rod treadmill test, was not impaired by bilateral ACC lesions. These results implicate that the ACC area of the brain plays differential roles in the mediation of different levels of spontaneous pain-related behaviors. The present study also provides additional evidence for the ACC-mediated descending facilitation of primary hyperalgesia (pain hypersensitivity) identified in the injured area under inflammatory pain state.