Chronic exertional compartment syndrome (CECS) is a condition in which muscle tissue expands against the surrounding fascia during activity and is compressed along with the nerves and blood vessels within the muscle compartment leading to abnormally high intracompartmental pressure (ICP) and debilitating pain. Treatment typically includes fasciotomy, which has significant levels of recurrence; however, botulinum toxin A (BoNT-A) injection has recently been seen to decrease both ICP and pain through an unknown mechanism with little to no recurrence. In this study, COX-1, COX-2, EP4, eNOS, and iNOS and either BoNT-A light chain or heavy chain were analyzed through docking models via Rosetta in order to determine their probability of interaction, and the EP4/BoNT-A heavy chain combination was found to have reaction scores most comparable to known interactions of BoNT-A. Based on this data, the effect of BoNT-A on cyclic adenosine monophosphate (cAMP), a downstream secondary messenger of EP4, in human skeletal myoblasts was analyzed through a cAMP direct immunoassay. Levels of cAMP consistently increased in myoblasts treated with BoNT-A, but the results were not significant. Several limitations were present within this study, so more research is needed to determine the interaction of BoNT-A and the EP4 pathway in muscle cells and the implications this may have on CECS and its treatment.

Analysis of botulinum toxin A and interacting proteins in skeletal muscle cells: Investigation into the mechanisms behind botulinum toxin A as a treatment for chronic exertional compartment syndrome

ACS Spring 2022

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