Peripheral Mechanisms Contributing to Spasticity and Implications for Treatment

Histolopathological studies have demonstrated a generalized increase in extracellular connective tissue in spastic muscles. It is known that increased connective tissue in an immobilized and contracted muscle reduces its compliance and could reduce the threshold for stimulation of spindle receptors in the muscle. Various authors have investigated how increased stretch-induced stimulation of spindles in muscles with stiffer connective tissue can contribute to spasticity. In this review, we compile evidence for the idea that the primary injury to the central nervous system that leads to muscle paresis also triggers changes in the viscosity of the extracellular matrix due to abnormal turnover of hyaluronic acid. Hyaluronic acid is a complex molecule that exhibits non-Newtonian behavior at higher concentrations, leading to altered connective tissue viscosity, which begins a vicious circle that exacerbates spasticity through reduced tissue compliance and potentiation of reflex mechanisms and fibrosis, and contributes to abnormal limb posturing, pain symptoms, and decreases in activities of daily living. The rationale for emerging treatments to break this vicious circle are discussed.