Opportunities in rehabilitation research

INTRODUCTION The Department of Veterans Affairs (VA) Office of Research and Development convened a group of experts (authors on this guest editorial) to identify key rehabilitation research opportunities. Our first task was to examine the important themes of rehabilitation research to serve as a guide to the identification process. Rehabilitation research encompasses a broad field of disciplines and methodologies covering the full spectrum of basic to applied science. Important themes for rehabilitation research include prevention, improvement, restoration, and replacement of underdeveloped or deteriorating function [1]. The use of the term "function" refers to the level of impairment, activity, and participation as defined by the World Health Organization [2]. An anonymous reviewer of this editorial noted that rehabilitation researchers are practitioners and investigators of the "science of recovery." Rehabilitation research operates within three domains of investigation: (1) physiological function (molecule, cell, tissue, and organs), (2) physical and mental function, and (3) social and community integration and design and delivery of rehabilitation services [3]. In defining areas of research opportunity, we do not intend to suggest an exclusive focus on the proposed topics and we fully support other creative approaches. Within each of the three domains of investigation identified previously, this editorial provides examples and highlights areas of interest but does not fully describe each potential research area of interest, nor does it cover all areas. PHYSIOLOGICAL FUNCTION (MOLECULE, CELL, TISSUE, AND ORGANS) It is important to understand the mechanisms of disease or injury relating to impairment. In considering research opportunities, we identified seven areas within the domain of physiological function (Figure 1). Molecular Substrates for Recovery and Preservation of Function An example of the molecular substrates for recovery relates to the process of demyelination in patients with multiple sclerosis (MS). The finding that a persistent current mediated by abnormally long regions of expression of Nav1.6 sodium channels triggers axonal degeneration in animal models of MS [4] has provided the basis for current clinical studies on sodium channel blockers as potential neuroprotective agents in MS [5]. Likewise, understanding molecular substrates for recovery and preservation of function is critical for developing treatments for spinal cord injury (SCI) and traumatic brain injury (TBI) and in all other areas of rehabilitation research. Figure 1. Areas of opportunity in rehabilitation research: molecule, cell, tissue, and organs. 1. Molecular substrates for recovery of preservation of function. 2. Identification and targeting of key molecules along pathogenic pathways. 3. Axonal sprouting, synaptic plasticity, regeneration, and functional compensation. 4. Drug, gene, and cell-based therapies for recovery of function and interaction with rehabilitation strategies. 5. Genetics and genomics, genomically based personalized therapies. 6. Muscle function, muscle disease (e.g. sarcopenia), and motile biological systems. 7. Bone healing and disease. Identification and Targeting of Key Molecules Along Pathogenic Pathways Changes in potassium channel expression in demyelinated fibers have been demonstrated in the demyelinating diseases [6]. These studies provided the rationale for the development of the potassium channel blocker, 4-aminopyridine, as the first Food and Drug Administration (FDA)-approved therapy for restoring function in MS [7]. Understanding cellular physiological changes in both animal models and in people with disabilities has also led to deep brain stimulation, the most significant advance in the treatment of Parkinson disease (PD) since the introduction of L-DOPA in the 1960s [8-9]. Neurophysiological analysis of both nonhuman primates treated with the toxin MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) as well as patients with PD identified over-activity in brain regions such as the subthalamic nucleus and the globus pallidus interna as a major contributor to abnormal motor function [10]. …