Suppression of nociceptive responses in the primate by electrical stimulation of the brain or morphine administration: behavioral and electrophysiological comparisons.
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Biomedical subjects
Publications and source records attributed to D D Price.
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These studies examined the effects of bilateral lesions of the dorsolateral funiculus (DLF) of the rat spinal cord on the inhibition of a nociceptive reflex produced either by a systemic injection of 4 mg/kg of morphine or by a 20 sec exposure to 1.0 mA of transcutaneous electric shock. Reflex inhibition was quantified and analgesia inferred by use of a modified version of the D'Amour-Smith tail-flick test. Lesions which included only the DLF reduced morphine-produced analgesia (MA) by 73% but had no effect on shock-produced analgesia (SA) observed in the same rats. Baseline tail-flick latencies of this group were not affected by the lesions. Control lesions restricted to the dorsal columns attenuated neither MA nor SA. Lesions which included both the dorsal columns and DLF did not affect SA and produced no greater reduction in MA than lesions of the DLF alone. Previous work indicates that both MA and SA result, at least in part, from supraspinal activity. The current data indicate that: (1) supraspinal modulation participating in two different types of analgesic induction involves separate descending spinal pathways and (2) the maximal expression of analgesia produced by administration of narcotics requires the integrity of a supraspinal neural system projecting in the DLF.
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Temporal summation of second pain and long-lasting tactile-evoked aftersensations are examples of sensory phenomenons that cannot be explained on the basis of responses of primary afferents. Two distinct classes of monkey spinothalamic tract neurons have responses to controlled natural stimuli that parallel and thus could account for the above phenomenons. One class, termed wide-dynamic-range, receives excitatory effects from sensitive mechanoreceptive afferents and from various nociceptive afferents including Adelta and C mechanothermal nociceptive afferents. Another class, termed nociceptive-specific, receives excitatory effects exclusively from primary nociceptive afferents. Both classes respond with an early and late response to a single noxious heat pulse (peak temperature = 51 C). The late response, unlike C nociceptive afferents but like second pain, summates in magnitude with each successive heat pulse. Gentle moving tactile stimuli evoke long-lasting (20-56 sec) after-discharges only in wide dynamic range neurons, and are similar in duration to the tactile after-sensation evoked by similar stimuli. Both the after-discharges and after-sensations can be abruptly terminated by rubbing the affected region. Temporal summation of second pain and cutaneous after-sensations are at least partly subserved by spinal cord mechanisms within the dorsal horn and are manifested in the output of spinothalamic tract neurons.
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1. A total of 113 trigeminothalamic neurons and over 200 presumed interneurons of nucleus caudalis (0-5 mm below the obex) and subjacent reticular formation were studied in rhesus monkeys anesthetized with chloralose or nitrous oxide. Each cell was characterized in terms of its antidromic responses to stimulation of ventral posterior medial and/or posterior thalamic nuclei and to three types of stimuli applied to its receptive field: a) graded 5-s temperature shifts at a rate of 9 degrees C/s from 35 degrees C to final temperatures of 20-52 degrees C, generated by a contact thermode; b) graded intensities of electrical stimulation to determine the conduction velocities of converging primary afferent fiber populations; and c) mechanical stimulation ranging from light touch to pinch with serrated forceps. 2. This analysis yielded five classes of units distinguished by the range of responses to mechanical stimuli and by the convergence of different primary afferent fiber populations. These five classes were found among both trigeminothalamic neurons and neurons which could not be antidromically activated. Class 1 units exhibited rapidly adapting responses to hair movement or light touch and received only A-beta primary afferent input. Class 2 units responded to light touch and pressure with maintained discharges and received A-beta primary afferent input. Class 3 units responded maximally to pinch with serrated forceps but also were activated by light touch and pressure. They received A-beta, A-delta, and C fiber input. Class 4 units responded to firm pressure and maximally to pinch with serrated forceps. These units had A-delta and sometimes C fiber input. Class 5 units responded only to pinch with serrated forceps and had exclusive A-delta fiber input. Some cells in all five classes responded antidromically to stimulation of the thalamus. Antidromic action-potential latencies of classes 1,2, and 3 units were shorter than those of classes 4 and 5 units (P less than 0.001). Receptive-field sizes were usually small (1-2 cm2) for classes 1, 2, 4, and 5 units, and larger for class 3 units (one to three trigeminal divisions). The marginal layer of nucleus caudalis contained mostly classes 4 and 5 units, some class 3 units, but no classes 1 or 2 units. The superficial portion of the magnocellular layer contained mostly classes 1 and 2 units, while neurons at the base of this layer contained class 3 units and some classes 4 and 5 units. Cells in the sujacent reticular formation included all 5 classes but showed a tendency to have large receptive fields (greater than 1 trigeminal division). 3. Neurons responding to noxious thermal stimuli (44-52 degrees C) were classes 3 or 4 units. The response patterns of classes 3 and 4 units to noxious thermal stimuli were similar. No classes 1 or 2 units and only one class 5 unit responded to increases in skin temperature. Thermal thresholds ranged from 38 to 50 degrees C and most heat-responsive units responded monotonically to temperatures between 45 and 52 degrees C...
Two general mechanisms based on anatomical studies are possible for modulation of motor activity by the caudate nucleus and globus pallidus. These mechanisms are: (1) modulation of the output of cortical neurons that exert motor influences; and (2) modulation of subcortical neurons that exert motor influences. Differentiation between these two mechanisms was accomplished in the present study by two experimental approaches, both of which employed the conditioning-test paradigm. The first approach was an investigation of caudate nucleus or globus pallidus modulation (conditioning stimulus) of flexor responses of the anterior tibialis muscle elicited by electrical stimulation of the sensorimotor cortex (test stimulus) or pyramidal tract (test stimulus). These investigations were carried out in the intact and in decorticate cats. The second approach was an analysis of modulation or cortically induced pyramidal tract responses (direct and indirect, D-I potentials) by conditioning shock trains delivered to various loci within the caudate nucleus or globus pallidus. Both approaches were designed to determine whixh inhibitory and facilitatory motor influences of the basal ganglia occurred at a cortical or subcortical level. Simultaneous stimulation of a locus within the caudate nucleus and the sensorimotor cortex evoked either an enhancement, reduction or no alteration of the cortically induced increase in flexor responses (measured by Ia afferent activity, EMG, myogram). In contrast, no inhibitory influences occurred from caudate nucleus stimulation upon pyramidal tract induced flexor responses in either the intact or decorticate preparation. Inhibitory loci were distributed toward the rostral portion of the caudate nucleus, whereas facilitatory loci were distributed throughout; this distribution was statistically significant (chi2; P less than 0.01). Only enhancement or no influence upon cortical induced or pyramidal tract induced responses were obtained by conditioning stimuli to the globus pallidus. In the unanesthetized but immobilized cat, trains of shocks delivered to the caudate nucleus enhanced, reduced or had no influence upon the cortically evoked direct (D) and indirect (I) potentials recorded in the bulbar pyramidal tract. The distribution of facilitatory and inhibitory loci was organized in a similar fashion as in theanesthetized preparation. From these observations, a model was proposed in which the output of the caudate nucleus exerts both facilitatory or inhibitory modulation of the tonically active globus pallidus cells. The latter in turn predominantly or exclusively facilitate output of pyramidal tract neurons as well as the output of subcortical structures; both effects facilitate motor responses at the spinal level.
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A sensitive quantitative index for predicting optimal electrode position in percutaneous anterolateral cordotomy was determined by electrical stimulation through the lesioning electrode. If the threshold for pain elicited by the stimulation electrode was less than 300 muA, a 5-sec radiofrequency lesion of 50 mA would produce complete contralateral analgesia with no weakness. When the pain threshold exceeded 300 muA, incomplete or no analgesia would result with the standard single lesion. The results further suggested that the fibers in the anterolateral quadrant that transmit pain are discretely rather than diffusely localized.
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