Role of Anterior Cingulate Cortex in the exacerbated facial response to mechanical stimuli as a sign of early orofacial neuropathic pain

The study of orofacial neuropathic pain necessitates the use of innovative assessment techniques, such as the facial expression of pain, which mirrors the internal state of the animals and could be utilized to identify the neural correlations involved. The Anterior Cingulate Cortex (ACC) is a crucial center in the processing of sensory and affective components of acute and neuropathic pain. However, its role in the facial response to pain remains a mystery. In this project, we set out to determine the changes in the facial response of early trigeminal neuropathic pain and the contribution of ACC in this process. We evaluated the facial response to mechanical stimulation using a machine-vision analysis in a head-fixed system before and after mental nerve compression in C57BL/6 mice. The role of ACC in the facial response was characterized via acute electrophysiological recording, and both glutamatergic ACC neural-ablation and optogenetic inhibition in a cre-dependent manner. Our results indicate that trigeminal nerve injury leads to an exacerbation of the intensity of the pain-like facial response to aversive stimuli in an early period. ACC neuronal activity is modulated by mechanical stimulation and during the dynamics of the facial response in different proportions before and after the lesion onset. The neuropathic pain-induced changes in the intensity of the facial response are nullified by the ablation or optogenetic inhibition of ACC glutamatergic neurons. Our study underscores the significant role of ACC in the development of signs of orofacial neuropathic pain, such as exacerbated facial response to mechanical stimuli. PERSPECTIVE: This article presents evidence on the sensory coding of mechanical stimulation in a neuropathic pain model in the Anterior Cingulate Cortex, using facial expression as a manifestation of the internal painful state. This evaluation provides a novel approach to evaluating the well-being of animals with neuropathic pain.