Incomplete spinal cord injury in man is followed by a number of debilitating disturbances in the control of movement, including spasticity, muscular weakness and muscle incoordination. There are related abnormalities in reflex pathways, ranging from augmented flexion withdrawal reflexes elicited by cutaneous and high threshold muscle afferent stimulation to loss of other segmental reflexes, especially those associated with autonomic control of the viscera. These abnormal reflexes may be manifested visibly, as painful flexor spasms. Alternatively, the effects of abnormal reflex function may be less obvious, yet still greatly impair muscle contraction by altering the rates and patterns of motor unit discharge within individual muscles. Finally, adverse effects may arise because of alterations in the spatial and temporal control of muscle activation in different muscles. Our research program is motivated by a number of recent findings regarding the physiology and pharmacology of the reflex systems that are impaired in incomplete spinal cord injury, including new information about afferent inputs, synaptic effects on segmental interneurons, descending pathway controls and especially the neurotransmitters of afferents and interneuronal systems. For example, regulation of many segmental interneurons is provided by descending monoaminergic systems (both 5HT and NE), whose effects would be lost or reduced in partial spinal cord transection. It is also likely that the synaptic effects of free nerve ending afferents, which exert powerful synaptic excitation on regional interneurons can be manipulated by agents such as capsaicin which damages terminal of small myelinated and unmyelinated fibers. Each of these findings represents fruitful possibilities for therapeutic intervention in spinal cord injury in man. The object of the research described in this proposal is to develop a better understanding of the physiological and pharmacological substrates for disturbances in segmental spinal cord function that follow incomplete spinal cord injury, in order to design therapeutic interventions that diminish the adverse impact abnormal reflexes play in the clinical state of the injured human subject. It is out intent to develop candidate agents suitable for testing in animal and eventually in human models.
| Saxena, P; Goldstein, R; Isaac, L (1997) Computer simulation of neuronal toxicity in the spinal cord. Neurol Res 19:340-8 |
| Morrison, S F; Ge, Y Z (1995) Adrenergic modulation of a spinal sympathetic reflex in the rat. J Pharmacol Exp Ther 273:380-5 |
| Ristic, H; Isaac, L (1994) Pharmacological characterization of dynorphin A (1-17)-induced effects on spinal cord-evoked potentials. J Pharmacol Exp Ther 270:534-9 |
| Kirsch, R F; Boskov, D; Rymer, W Z (1994) Muscle stiffness during transient and continuous movements of cat muscle: perturbation characteristics and physiological relevance. IEEE Trans Biomed Eng 41:758-70 |
| Rymer, W Z (1993) Spinal cord injury: physiology and transplantation. Adv Neurol 59:157-62 |
