We established that hyper-reflexia is delayed after spinal transection in the adult rat, and that passive exercise could normalize low frequency-dependent depression of the H-reflex. We were also able to show that such passive exercise will normalize hyper-reflexia in patients with spinal cord injury (SCI). Recent results demonstrate that spinal transection results in changes in the neuronal gap junction protein connexin 36 below the level of the lesion. Moreover, a drug known to increase electrical coupling was found to normalize hyper-reflexia in the absence of passive exercise, suggesting that changes in electrical coupling may be involved in hyper-reflexia. We also present results showing that a measure of spasticity, the stretch reflex, is rendered abnormal by transection and normalized by the same drug. These data suggest that electrical coupling may be dysregulated in SCI, leading to some of the symptoms observed. A novel therapy for hyper-reflexia and spasticity may require modulation of electrical coupling.

Spasticity is evident in both humans and animals following spinal cord injury (SCI) and can contribute to significant functional limitation and disruption in quality of life of patients with this disorder. This mini-review describes a number of preclinical and clinical studies that promise to improve outcomes for, especially in terms of spasticity and hyper-reflexia, patients with SCI. A gold standard for the quantification of spasticity has proved elusive, but the combination of H-reflex frequency dependent depression and a novel stretch reflex (SR) windup protocol have the potential to provide new insights. As the pathophysiology of hyper-reflexia and spasticity continue to be investigated, the documented onset in the animal model of SCI provides critical time points for further study into these complex mechanisms. The positive effects of a passive exercise protocol and several potential pharmacological interventions are reviewed as well as a novel potential mechanism of action. Further work is needed to determine additional mechanisms that are involved in SCI, and how to optimize multiple therapies to overcome some of the deficits induced by SCI.