The Impact of Chronic Pain on the Medial Prefrontal Cortex : Mechanisms and Treatments

Chronic pain patients suffer from deficits in cognitive performance even while taking commonly prescribed analgesics. Given that higher executive functioning is dependent upon an intact medial prefrontal cortex (mPFC) suggests that maladaptive cortical plasticity is occurring in this region. Reductions in PFC gray matter volume and enhanced PFC hemodynamic response have been observed in numerous neuroimaging studies of chronic pain patients; while studies in rodents with neuropathic pain have revealed changes in synaptic plasticity, functional connectivity, morphology, and gray matter volume of the mPFC. Despite this work, changes in mPFC plasticity have not been linked directly to behavioral outcomes in chronic pain models, and little is known about the causative molecular pathology, or the influence of analgesic strategies on mPFC performance in chronic pain. The goal of our research was to generate a preclinical rodent model of neuropathic-pain induced cognitive impairment as a tool for assessing analgesic efficacy and morphological changes in the mPFC that underlie cognitive dysfunction in neuropathic pain. Our findings reveal that neuropathic pain-related cognitive impairment is sexual dimorphic, characterized by bilateral morphological changes in the length of axon initial segments, and reversed by analgesics that target translation dysregulation.