COBRE Phase III Year 5 Pilot: Evaluation of the Effect of Botulinum Toxin on Orofacial Neuropathic Pain: A Preclinical Study

Patients with trigeminal neuropathic pain (TNP) have impairments in physical and psychological functioning that undermine their quality of life. Management of TNP remains challenging even though research in the pain field has focused on understanding plasticity changes in the nervous system associated with neuropathic pain. Recently, animal studies have supported potential use of onabotulinum toxin A (BoNT/A) in treatment of TNP. In addition, clinical case series have suggested that BoNT/A may have an analgesic effect in patients suffering from TNP. However, even with results of these animal experiments and clinical trials, there are no definitive pharmacologic or surgical treatments for TNP. Therefore, understanding the underlying pathology of TNP is necessary for the development of more effective therapies. Recent studies indicated that glial cells play an important role on the pathogenesis of neuropathic pain. Investigations of glial cell signal transduction may expand understanding of underlying mechanisms associated with development and maintenance of TNP. The hypothesis for this project is that BoNT/A attenuates orofacial neuropathic pain through blocking signal transduction of the central and peripheral nervous system. Primary objectives of this project will determine effects of BoNT/A administration on onset and maintenance of pain in a model of TNP, trigeminal inflammatory compression nerve (TIC) injury in mice (Aim 1) and to identify neuronal and glial signaling mechanisms of its analgesic effect in this model (Aim 2). Upon completion of these studies we will be positioned to provide insights into the pathophysiology of TNP and the analgesic effect of BoNT/A on TNP.