DEVELOPMENT OF A MODEL FOR THE ASSESSMENT OF SOMESTHETIC SENSITIVITY IMPAIRMENT IN HUMAN AND NONHUMAN PRIMATES: NORMATIVE DATA AND APPLICATIONS TO THE STUDY OF DRUGS AND TOXIC CHEMICALS.

摘要

Numerous physical, chemical and biological agents are known to produce cutaneous sensory symptoms usually associated with peripheral nerve disorders. Biochemical, morphological, electrophysiological and clinical studies have attempted to define the exact nature of these neurotoxic effects. The approach I chose can be referred to as psychophysical approach. It consists in the scientific study of the relations between stimuli and resulting sensations, and can be used with human as well as nonhuman primates.;Sensitivity is assessed in the following manner. The monkey sits in a restraining chair in front of a small table. The left had is immobilized in a plasticene mold. The tip of the middle finger is placed on vibrating probe that protrudes through a hole. The right hand is free and has access to a telegraph key. A spout next to the monkey's mouth delivers fruit juice when an electromagnetic valve is activated.;Similarly, the human subject sits on a chair facing a table. Instruction is given to keep the left hand in a relaxed position with the tip of the middle finger on the vibrating contactor. The right hand has access to a telegraph key. Verbal instructions are given to the subject about the task requested.;The testing session is divided into discrete trials. A tone is turned on. The subject presses the key, holds it down, and, after a variable interval, vibration is delivered to the finger. A key release during vibration is rewarded either by fruit juice (monkeys) or by the addition of a point to a counter (humans). Catch trials are randomly introduced in the testing session in order to get a quantitative estimate of guessing bias. Normative data have been obtained in monkey and humans.;Cutaneous sensations are heterogeneous and cannot be described adequately in terms of a single cutaneous sensory quality. However, I chose vibration sensitivity, which presented several advantages. Vibration sensitivity involves at least two different sets of end organs and nerve fibers. Deep receptors, and, supposedly, more superficial ones, are excited by vibration. Furthermore, several chemicals, such as acrylamide and methylmercury, can selectively cause partial loss of or damage to large myelinated fibers. Since vibratory information travels through such fibers, an insult of this nature would result in decreased vibratory sensitivity. A computerized system for an accurate and automated study of vibration sensitivity was therefore designed and developed. It has been employed with both monkeys and humans.;One human subject received, in a blind experiment, several doses of the local anesthetic carbocaine. The time course of the effects of the drug on vibration sensitivity was studied and a dose-effect curve obtained.;Two monkeys received the drug misonidazole and showed a decreased vibration sensitivity. Patients receiving the same drug also displayed elevated thresholds after receiving high nuerotoxic doses.;Two other monkeys received methylmercury chronically. A decrease in vibration sensitivity occurred without any other detectable signs of intoxication such as weight loss or motor incoordination. Changes in vibration sensitivity seem to be an early sign of poisoning.;In conclusion, vibration sensitivity, as assessed by the technique described here, presents several advantages and can be used as a model for the study of somesthetic dysfunction induced by neurotoxic chemicals. Data collected under control conditions show a remarkable consistency over time in humans as well as in monkeys. Furthermore, since monkeys share many functional and anatomical characteristics with humans, and their sensitivity is indistinguishable from that of humans, monkeys studied with this technique represent an excellent model of human vibration sensitivity. Application of this model to toxicity studies is likely to provide meaningful data directly applicable to the human situation.