879 Novel injectable coolant for reducing cutaneous nerve fiber density

Abstract

Postherpetic neuralgia (PHN) is a dermatologic disorder with no established cure. The distinct dermatomal distribution of PHN makes the peripheral nerve supplying the dermatome and its distal cutaneous branches the ideal therapeutic target; however, the short acting nature of current medications limits the use of this localized approach. Herein we demonstrate the effects of a drug-free, injectable coolant with long-lasting pain suppression capabilities that could potentially be used for treatment of PHN. We have previously reported reduced cutaneous nerve fiber density following topical cooling with cryolipolysis treatment. From here we went on to develop an injectable coolant to target nerves at any anatomic location accessible by a needle. We showed that injection of coolant around the rat sciatic nerve leads to local disruption of myelin. This in turn leads to decrease in nocifensive function for up to 60 days. In this study, using the rat sciatic nerve, we examined the mechanism of reduced nociceptive response after coolant injection. We investigated the effects of the injectable coolant on sciatic nerve branches distal to the injection site and on cutaneous nerve fibers using Coherent anti-Stokes Raman scattering (CARS) microscopy and immunofluorescence (IF) staining. CARS showed myelin degradation in branches distal to the injection site. Corrected correlation parameter index, an indicator for organization of myelin structure, decreased in fibular branch from 0.86±0.08 at baseline to 0.40±0.22 (P<0.0001) at day 14 post injection. Myelinated dermal nerve fiber density was quantified in skin of the hind paw innervated by the sciatic nerve. IF staining showed decreased density of myelinated dermal nerve fibers from baseline value of 56±3/mm2 to 22±3/mm2 (P<0.0001) at day 14. Thus, coolant injection reduces pain by decreasing cutaneous nerve fiber density. Although more work needs to be done, we hope this could potentially be used to treat PHN associated pain.