Orofacial pain encompasses a multitude of disorders, including temporomandibular disorders (TMD), trigeminal neuralgia, headaches (e.g., migraine, tension-type), and myofascial pain, and affects an estimated 20% of the U.S. population. Despite the financial and emotional magnitude of orofacial pain, however, only a limited number of relevant animal models and behavioral assessment techniques have been developed, and relatively few model a human's pain experience and cognitive processing. Our long-range goal is to establish translational models that allow for evaluation of pain within the trigeminal system and to simulate clinical disorders in order to investigate novel analgesic agents. The objective of this particular application is to evaluate operant behavioral assays for assessing trigeminal pain. The central hypothesis for the proposed research is that these operant behavioral assays can provide a sensitive, clinically relevant way to evaluate trigeminal sensory and nociceptive processing.
Two specific aims will be investigated:
Aim #1, to evaluate an operant model of thermal hyperalgesia and allodynia for evaluating trigeminal nerve mediated pain;
and Aim #2, to investigate the effects of opioid and non-opioid mediated analgesia on thermal operant orofacial outcome measures. We will test these aims using an experimental approach using a highly innovative behavioral thermal strategy that involves an operant-conditioning paradigm. This includes: (1) a facial thermal reward-conflict strategy for assessing thermal allodynia and hyperalgesia; and (2) pharmacologic evaluation of the thermal outcome measures. We will use these measures in models of orofacial inflammation, neuropathic pain, and neurogenic inflammation. In these assays, the animal has control over the amount of nociceptive stimuli it will receive and can thus modify its behavior based on a number of factors, including those involving cortical processing. Collectively, these methods will provide noninvasive, quantifiable outcomes of trigeminal pain conditions that better model human experiences. Successful application of these novel behavioral testing strategies will provide a significant advancement in research strategies for understanding mechanisms of orofacial pain disorders. These proposed studies will provide a basis for behavioral studies within the trigeminal system that can be used as a correlate for future studies investigating molecular and physiological markers of pain, thus providing a pivotal link for translating basic pain research into clinic trial strategies. ? ?
