361 Effect of intravenous psilocybin on mechanical hypersensitivity in a rat model of reserpine-induced chronic centralized pain

Objectives/Goals: We recently showed that a single dose of psilocybin, a serotonergic psychedelic, attenuated mechanical hypersensitivity for up to 28 days in a rat model of formalin-induced chronic centralized pain. The goal of this study is to determine whether psilocybin can alleviate chronic pain in a rat model of reserpine-induced chronic centralized pain. Methods/Study Population: Adult Sprague-Dawley rats (male=12, female=12) will be surgically equipped with a chronic indwelling catheter in jugular vein for the delivery of psilocybin. After 14 days of post-surgical recovery, rats will undergo Randall–Selitto testing to assess their baseline muscle pressure threshold. Thereafter, the rats will receive subcutaneous reserpine (1mg/kg) for three consecutive days, which depletes biogenic amines that have been reported to be reduced in fibromyalgia patients. The rats will be tested again on the Randall–Selitto assay on post-reserpine days 1, 3, 5, 7, 14, 21, and 28. One subgroup of the rats will receive intravenous psilocybin (1mg/kg) on post-reserpine day 4, while the other subgroup will receive intravenous saline. Results/Anticipated Results: We have completed data collection from four female rats which shows that compared to baseline, reserpine reduced muscle pressure threshold on post-reserpine days 1–21 (mean ± SD, day 1: -18.33%±7.26%, day 3: -15.05%±7.2%, day 5: -29.19%±3.75%, day 7: -19.64%±14.67%, day 14: -30.02%±10.14%, day 21: -14.95%±12.9%). On day 28, muscle pressure thresholds approached baseline levels (-8.12%±14.73%). These data show that we have successfully reproduced the reserpine model in our laboratory. Based on our previous study showing alleviation of mechanical hypersensitivity in formalin-treated rats after a single dose of intravenous psilocybin, we expect that psilocybin will shorten the duration of reserpine-induced mechanical hypersensitivity as compared to the rats receiving 0.9% saline as vehicle control. Discussion/Significance of Impact: These studies are expected to provide a neuroscientific foundation for the emerging use of serotonergic psychedelics as a potential treatment for chronic pain conditions, including fibromyalgia.