Research reportActivation of astrocytes in the anterior cingulate cortex contributes to the affective component of pain in an inflammatory pain model

The anterior cingulate cortex (ACC) has been implicated as a key structure in the affective component of pain (such as unpleasantness or aversion). Recent evidence suggests that activation of spinal astrocytes contributes to the development and maintenance of the sensory component of pain after peripheral inflammation. However, whether the astrocytes in the ACC contribute to the affective component of pain is unknown. In this study, we demonstrated that intraplantar administration of Complete Freund's Adjuvant (CFA) in rats induced mechanical allodynia and place escape/avoidance behavior, which reflects the aversion of mechanical nociceptive stimuli. A reverse transcriptase-polymerase chain reaction study showed a significant increase in the mRNA level of GFAP, an astrocytic marker in the bilateral ACC at 3 d and 14 d after CFA-induced peripheral inflammation. Similarly, Western blot also revealed enhanced expression of GFAP protein at 3 d and 14 d after CFA injection. Interestingly, intra-ACC injection of L-alpha-aminoadipate (L-α-AA), an astroglial toxin, inhibited the escape/avoidance behavior, but did not affect the paw withdrawal threshold at 3 d following CFA injection. All together, our results suggest that the astrocytes activation in the ACC may contribute to the affective component of pain.

► Peripheral injection of Complete Freund's Adjuvant (CFA) induced both sensory and affective pain. ► Astrocytes in the bilateral anterior cingulate cortex (ACC) were activated by periphral injection of CFA. ► Intra-ACC injection of astroglial toxin blocked the animal's affective component of pain, but not the sensory component of pain. ► This is the first study specifically addresses the role of astrocytes activation in the ACC in the affective component of pain.