Spinal cord injury pain: spinal and supraspinal mechanisms.

INTRODUCTION Sensory abnormalities, including pain, associated with spinal cord injury (SCI) are related to the nature of the lesion, damaged neurological structures, and secondary pathophysiological changes of surviving tissue [1-3]. Although complete loss of sensory and motor functions is thought to most significantly affect individuals with spinal injury, secondary complications that include spasticity, bladder and bowel dysfunctions, infertility, autonomic dysfunction, and pain are among the most difficult consequences to deal with following injury [4]. Over the past 15 years, a systematic examination related to the pathophysiology, clinical characteristics, and treatment of different pain conditions has provided insight into the potential mechanisms contributing to the onset and maintenance of above- and below-level pain associated with SCI [5]. The development of experimental models to study spinal injury combined with clinical studies has provided important information related to spinal and supraspinal changes contributing to the development of at- or below-level pain. At the site of injury, multicomponent excitotoxic and inflammatory cascades affect the survivability and functional state of spinal neurons. Changes in the excitability of neurons secondary to the release of inflammatory mediators along with a decrease in local inhibitory influences and changes in descending modulation provide a permissive environment that leads to the development of spinal pain generators that contribute to the mechanism of injury-induced pain. In this review, I will discuss experimental studies that focus on the spinal and supraspinal mechanisms associated with at- and below-level neuropathic pain. Pain of musculoskeletal, radicular, visceral, or psychogenic origins all are significant in the clinical sequela of spinal injury. These pain syndromes are discussed elsewhere [6-11]. SCI PAIN: RESEARCH STRATEGIES AND EXPERIMENTAL STUDIES A cascade of cellular, biochemical, and molecular responses to SCI is significant in producing functional changes that contribute to the onset of abnormal sensations, including pain, following spinal injury [2-3,12]. Considering the traumatic and/or ischemic insult associated with injury to the spinal cord parenchyma, one is not surprised that the pathological sequela of injury includes a wide spectrum of events that severely compromise the anatomical and functional integrity of sensory, motor, and autonomic pathways in the spinal cord. Another consideration is the physical factors, including completeness and level of injury, that correlate with pain onset. Unfortunately, few consistent predictors have been identified [1,13], although a positive relationship between the higher incidence of pain in patients with thoracolumbar and incomplete lesions has been described [14]. Several models, including mechanical trauma, isolated lesions, complete transection, chemical lesions, and ischemic injury, each with pathological components found in the human condition, have been used in the study of SCI pain [15-18]. Many of the well-documented changes associated with different SCI models progress in a rostrocaudal direction and influence not only spinal but also cortical and subcortical structures [2]. Given the wide range of pathophysiological changes associated with spinal injury, it is important to identify causal relationships between specific changes and the onset of pain as opposed to merely pointing out events occurring secondary to the injury process. Establishing these causal relationships is critical to identifying underlying mechanisms responsible for pain development. Selecting effective behavioral measures used to assess mechanical and thermal sensibilities following injury is another challenge in the study of different injury-induced pain conditions. Most behavioral measures used in the study of SCI pain have historically relied on reflex-based responses to peripheral stimuli. …