In view of growing interest in intrathecal drug administration as a means of modulating pain in humans and the lack of information pertaining to how this procedure affects the spinal cord, this application proposes studies of the local spinal cord blood flow (SCBF) and metabolic effects of intrathecally administered local anesthetics, opiates, and adrenergic agonists. Male, Sprague-Dawley rats will be prepared with a lumbar subarachnoid catheter and, 24-48 h later, femoral artery and vein catheters. Thereafter, experiments will be conducted in conscious, partially restrained rats; general physiologic state will be evaluated by arterial blood pressure, blood gas and pH, and temperature measurement. Experimental animals will receive drugs intrathecally in 10-15 ul of saline so as to prevent spread to supraspinal areas; control animals will receive only saline. Drugs will be administered in analgesic doses and the effect measured by latency of the tail-flick response. Agents to be examined include physiochemically different local anesthetics; opiates of different potency, lipid solubility, receptor affinity, or selectivity; selective and non-selective alpha adrenergic agonists; and some combinations of the above. In cases of positive results, additional experiments designed to pharmacologically antagonize the SCBF effect or dissociate it from analgesia will be performed. Local SCBF and/or metabolism will be measured during the period of analgesia with the quantitative, autoradiographic iodo-(14C)antipyrine and 2-(14C)deoxyglucose methods, respectively. These studies will provide basic, new information on spinal cord circulatory and metabolic physiology during intrathecal analgesia, and may help explain aspects of uptake and elimination of drugs from the subarachnoid space. The studies may also provide insight into the role of endogenous neurotransmitters in the regulation of SCBF and metabolism under physiologic and pathophysiologic conditions, and, possibly, help predict or explain the occasional untoward neurologic effects of administering drugs directly into the neuraxis.
| Crosby, G; Russo, M A; Szabo, M D et al. (1990) Subarachnoid clonidine reduces spinal cord blood flow and glucose utilization in conscious rats. Anesthesiology 73:1179-85 |
| Hurford, W E; Crosby, G; Strauss, H W et al. (1990) Ventricular performance and glucose uptake in rats during chronic hypobaric hypoxia. J Nucl Med 31:1344-51 |
