Review Neurobiological perspective of spasticity as occurs after a spinal cord injury ☆ Roland R. Roy a, c , V. Reggie Edgerton a, b, c, ⁎ a Department of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, CA, USA b Department of Neurobiology, University of California, Los Angeles, Los Angeles CA, USA c Brain Research Institute, University of California, Los Angeles, Los Angeles CA, USA abstract article info Article history: Received 11 April 2011 Revised 14 January 2012 Accepted 19 January 2012 Available online 27 January 2012 Keywords: Spinal cord injury Neuromuscular spasticity Spinal neuron excitability Pharmacological interventions In this review we use the term spasticity to mean the generation of abnormal patterns of forces that are gen- erated involuntarily. It is clear that spasticity can have both detrimental and beneficial effects on the neuro- muscular system of the affected individuals. Muscle spasticity routinely occurs after a spinal cord injury and other neurological disorders. Although often studied as if there was a single mechanism associated with this phenomenon, it is clear that there are multiple mechanisms having both neural and muscular components, particularly when such terms also are applied to other neuromotor disorders. The aims of this review are to describe the neural and muscular adaptations that are associated with spasticity, highlight the major possible mechanisms producing spasticity, and discuss the role of selected pharmacological interventions in controlling spasticity. Spasticity appears to be related to altered membrane channel and receptor proper- ties that are primarily associated with an increase in the excitability of spinal neurons, resulting in abnormal (in the intensity and combination of muscles activated) contractions that are generated involuntarily. While most of the efforts to understand the etiology of spasticity have focused on motoneurons, it is likely that spinal interneurons play a central role as well as the mechanical properties of muscle fibers and associated connective tissues. A number of pharmacological interventions have been used in attempts to suppress spas- ticity with varying results, but concomitant with suppressed muscle activation, there can be significant side effects including a reduction in the control of movement. © 2012 Elsevier Inc. All rights reserved. Contents Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 116 Spasticity as a function of motor unit recruitment within a motor pool and among motor pools . . . . . . . . . . . . . . . . . . . . . . . . . 117 Physiological consequences of neurally based muscle spasms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 117 Electrophysiological and pharmacological measures of spasticity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 118 The role of neuromuscular adaptations in the presence of spasticity after a SCI . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 118 Pharmacological modulation of spasticity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 119 Perspective . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 120 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 120 Introduction Although it is generally recognized that the term spasticity is used to describe multiple phenomena, the expectation frequently remains for there to be a single mechanism underlying spasticity. This provides a landscape for confusion and, therefore, efforts to pinpoint an underlying mechanism will be futile. There is sufficient evidence to conclude that the clinical symptoms typically categorized as spasticity are in fact multiple clinical phenomena and have multiple mecha- nisms that can be caused by multiple cellular dysfunctions. In looking ahead, therefore, it would be useful to think of spasticity not as a single Experimental Neurology 235 (2012) 116–122 ☆ Supported by the National Institute of Neurological Disorders and Stroke (NINDS), the National Institute Biomedical Imaging and Bioengineering (NIBIB), the Christopher and Dana Reeve Foundation, the Craig H. Neilsen Foundation, and the Roman Reed Fund of California. ⁎ Corresponding author at: Department of Integrative Biology and Physiology, Uni- versity of California, Los Angeles, 610 Charles E. Young Drive East, Los Angeles, CA 90095-7239, USA. Fax: +1 310 206 9184. E-mail address: vre@ucla.edu (V.R. Edgerton). 0014-4886/$ – see front matter © 2012 Elsevier Inc. All rights reserved. doi:10.1016/j.expneurol.2012.01.017 Contents lists available at SciVerse ScienceDirect Experimental Neurology journal homepage: www.elsevier.com/locate/yexnr