Right–side predominance of the central amygdala activation in trigeminal inflammatory pain model

The central amygdala (CeA), especially the capsular part (CeC), receives nociceptive information from the superficial layer of the spinal dorsal horn and the caudal subnucleus of the trigeminal nucleus via the lateral parabrachial nucleus (LPB). The synapse between LPB and CeC neurons, forming the final stage of this spino–(trigemino–)parabrachio–amygdaloid pathway, undergoes robust synaptic potentiation in various types of rodent pain models, thus contributing to the enhanced nociception–emotion link in persistent pain. A remarkable feature of the CeA activation in animals with inflammatory pain is the right–side predominance. Using a trigeminal pain model by injecting formalin to the upper lip unilaterally, we analyzed the right–left differences in LPB–CeC synaptic potentiation and c–Fos expression in the LPB and the amygdala to reveal what determines the right– predomi nance in CeA activation. Unilateral trigeminal inflammation induced 1 ) a significant bilateral increase in c–Fos–expression in the LPB, 2 ) a right–predominant LPB–CeC synaptic potentiation and 3 ) a right–predominant increase in c– Fos–expression in the CeA, regardless of the side of the inflammation. Though c– Fos expression in the basolateral amygdala (BLA) was not significantly increased in this model, the number of c–Fos positive cells between the BLA and CeA was cor-related compared to that between the LPB and CeA. Therefore, the right–side predominance of the CeA activation in the inflammatory pain models would not be a simple consequence of lateralized LPB activation but rather involves non–Hebbian plasticity inherent to the CeA neurons and inputs they receive.