407 Novel injectable coolant for treatment of pain

Abstract

Cutaneous pain management is an unmet need. Current treatment options include medications such as analgesics and narcotics, which have high risk of addiction, and limited success. A long-lasting, drug-free treatment for cutaneous pain is needed. We had previously shown that controlled topical cooling of the skin via cryolipolysis, leads to prolonged but reversible reduction in mechanical and thermal pain sensation. While topical cooling can be used for targeting superficial nerves of a confined area, blocking cutaneous pain with larger and dermatomal distributions could be achieved by targeting deeper nerves. We invented an injectable coolant for targeting deeper nerves as a novel treatment for pain. Using the rat sciatic nerve model, we studied the safety, feasibility and efficacy of the coolant in selectively and reversibly targeting the rat sciatic nerve. The coolant was injected around the sciatic nerve, and at various time points, the nerve was harvested for histologic and imaging studies. Coherent anti-Stokes Raman scattering microscopy showed myelin degradation followed by full recovery in 4 months. Quantification of degenerative nerve fibers showed significant increase in mean nerve degeneration score of 1.66 at day 7 post injection, 2.66 at day 14 post injection, with complete recovery at 4 months post treatment, (p<0.05). Immunofluorescence and electron microcopy showed degenerative changes in myelinated and unmyelinated axons, with complete recovery by 4 months. Sensory functional assays showed significant reduction of mechanical pain post treatment that lasted for 2 months. Thus, the injectable coolant is safe and effective in reversibly targeting the sciatic nerve for prolonged duration. We are now ready to test this in human clinical trials as a novel and long lasting treatment for pain.