1164 THE USE OF CHEMICAL NEURO STIMULATION TO MINIMIZE SLEEP DISTURBANCE ASSOCIATED WITH MUSCLE CRAMPING AND SPASTICITY

Muscle cramps are common in neurological disorders such as ALS, Charcot Marie Tooth neuropathy, multiple sclerosis, cramp fasciculation syndrome and Parkinson’s disease. Muscle cramping and, in the case of certain neurological disorders, associated spasticity disturb sleep impacting quality of life. FLX-787, a synthetically-prepared co-activator of TRPV1 and TRPA1, has been demonstrated to activate sensory neurons in the oropharynx and esophagus to decrease muscle cramp intensity. Chemical Neuro Stimulation of TRPV1 and TRPA1 is thought to stimulate brainstem relays to activate descending spinal pathways and ultimately inhibitory interneurons at the segmental level. Because muscle cramping stems from hyperexcitability of alpha motor neurons, activation of inhibitory interneurons in the spinal cord could decrease hyperexcitability and afford cramp relief. We sought to understand the prevalence and timing of nocturnal leg cramps during sleep and if Chemical Neuro Stimulation could limit nocturnal leg cramp frequency and severity to improve sleep quality. Two, randomized, blinded, placebo-controlled cross-over studies in healthy volunteers with a history of nocturnal leg cramps (n=50) were conducted to monitor the safety and efficacy of TRPV1 and TRPA1 co-activation. Additionally, a survey-based assessment (n=84) to monitor the duration of cramp relief after dosing was also performed. TRPV1 and TRPA1 co-activation either by natural TRP activators or FLX-787 led to an increase in cramp free nights/period and improvements in sleep quality and reduction in associated pain. Across studies, muscle cramping was observed throughout the night with slightly higher frequency during the latter portion of the night (6–8 h). Cramp inhibition by TRPV1 and TRPA1 co-activation was most prominent during the first four hours after dosing with noted decreases in cramp frequency during this time. The cramp survey results agreed with these findings with 56% of respondents experiencing relief in the first 4 hours after dosing. The results suggest that Chemical Neuro Stimulation is effective at increasing the number of cramp free nights which may lead to improved sleep and decreased pain. Chemical Neuro Stimulation may be a useful strategy to improve sleep quality in individuals suffering from cramps and spasticity associated with neurological disease. not applicable