Project 1: Resolving orofacial neuropathic pain evoked by compression of a trigeminal nerve branch using rationally integrated complementary approaches ABSTRACT Neuropathic pain in the craniofacial region innervated by trigeminal sensory neurons affects approximately at least 1x106 Americans. The goal of this project is to assess efficiency and elucidate key mechanisms of rationally-combined complementary approaches to treat trigeminal neuropathic pain. The central hypothesis of Project-1 is that natural pro-resolution lipid mediators (specialized pro-resolution lipid mediators, SPMs) or auricular electro-acupuncture (aEA) can produce beneficial effects in alleviating orofacial neuropathic pain, aggravated by stress, by modulating neuroinflammation and neural plasticity. We will use a well-established mouse model of trigeminal neuropathic pain, chronic constriction of the infraorbital nerve (CCI-ION), to test our central hypothesis. We will first define the time course of neuropathic pain and inflammatory and neuroinflammatory profiles in response to CCI-ION in both sexes with and without stress. Subsequently, we will determine the effects of aEA and SPMs on pain-related behaviors as well as resolution of inflammatory and neuroinflammatory profiles evoked by CCI-ION. Finally, we will explore effectiveness of aEA and SPMs on reducing spontaneous activity of trigeminal sensory neurons and of ongoing pain-activated CNS neurons after CCI-ION.