Elizabeth A. Dugan2 , David Budac2, Briana Stanfield2, Mark Urban2, Vicki E. Brings1, Sarah A. Woller1, Smriti Iyengar1, Taleen Hanania2, Mark A. Varney2
1Division of Translational Research, National Institutes of Neurological Disorders and Stroke, National Institutes of Health, Rockville, MD 20852
2PsychoGenics Inc., Paramus, NJ, 07652
In collaboration with the NIH HEAL Initiative Preclinical Screening Platform for Pain (PSPP), we evaluated clinically used compounds, including celecoxib, carbamazepine, and diazepam through the tiered approach established to profile potential novel analgesics. First, pharmacokinetic studies were conducted to guide dosing, select the route of administration, and to determine the time course, supporting subsequent behavioral studies. Next, the modified Irwin and rotarod tests were conducted to evaluate potential neurologic, physiologic, and fine motor effects that may impact outcome measures in the pain models. Following side effect profile assessment, efficacy was evaluated in the plantar incision and L5/L6 spinal nerve ligation (SNL) models. The rat plantar incisional pain model is an established model of acute post-operative pain induced by incision of the skin and the plantaris muscle (Brennan et al. 1996). The model is characterized by transient hind paw tactile allodynia and spontaneous guarding behaviors. SNL is a model of peripheral neuropathic pain resulting from chronic nerve compression in which tactile and cold allodynia are produced (Kim and Chung, 1992).