The functional consequences of spinal cord injury are often characterized in terms of motor capacities (e.g. weight support, walking, grasping). However, a variety of reflex abnormalities (generally characterized as spasticity) and somatosensory disorders (either loss or exaggeration) can result from spinal cord injury (SCI). Exaggeration of reflexes and sensations can represent the most disturbing functional consequences of SCI. Important goals of this proposal are to determine which spinal lesions are responsible for production of hyperexcitable reflexes and aversive sensations. In addition, a novel method of permanently attenuating aversive sensations (dysesthesias) after injury to a peripheral nerve or the spinal cord will be evaluated. An important feature of the proposed studies is direct comparison of reflex and sensory consequences of peripheral and spinal lesions in rats using newly developed methods for evaluating learned (operant) responses to aversive stimuli, in addition to innate (reflex) responses that are commonly evaluated. The sensory effects of restricted spinal lesions and therapeutic intervention will be tested also in primates, providing important comparisons between rodent and primate models of dysesthesia, and offering crucial tests of the therapeutic potential of spinal application of a selective neurotoxin for neurons with receptors for substance P. The neurons targeted by the substance P toxin contribute importantly to the rostral conduction of disturbing somatosensations. Selective elimination of these cells in spinal segments affected by a peripheral or spinal lesion potentially has considerable advantages over traditional ablative procedures. Ablative lesions of spinal white matter can produce dysesthesias and therefore are used in part to model this sensory abnormality in the proposed studies. Rats and monkeys will be trained to terminate (escape) thermal stimulation of their feet and then will be tested following partial injury to a peripheral nerve or restricted interruption of spinal pathways that have been implicated in production of dysesthesias. The animals will then receive an intraspinal application of substance P-saporin, the selective neurotoxin for neurons with receptors (NK-1R) for substance P. Subsequent testing will determine whether this procedure has normalized responses to thermal stimulation. The extent of surgical and neurotoxic spinal lesions will be related to effects on responses to thermal stimuli.
| Vierck, Charles J; Acosta-Rua, Antonio J; Rossi, Heather L et al. (2008) Sex differences in thermal pain sensitivity and sympathetic reactivity for two strains of rat. J Pain 9:739-49 |
