TOWARD A NEUROPHYSIOLOGY OF PAIN

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75094/1/j.1526-4610.1969.hed0804141.x.pd

Neural Mechanisms of Pain: an Overview

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65716/1/j.1399-6576.1982.tb01838.x.pd

Supraspinal nocifensive responses of cats: Spinal cord pathways, monoamines, and modulation

These experiments were conducted to determine (1) whether dorsal and ventral ascending spinal pathways can each mediate unlearned supraspinal nocifensive responses of cats to noxious thermal stimuli and (2) whether interrupting the spinal projection of supraspinal monoaminergic neurons alters the excitability and natural modulation of these responses. In partially restrained cats, thermal pulses (≥ 47°C) delivered to the hindlimbs of intact cats or rostral to lesions of the thoracic spinal cord elicited abrupt body movements and interruption of eating (or of exploring for) liquified food. These electronically monitored responses automatically terminated the stimulus. Natural modulation of responsiveness was produced by delivering food and thermal stimuli simultaneously; this reduced response probability by an average of 41%. Complete transection of the thoracic spinal cord eliminated both thermally elicited responses, and orienting responses to noxious and tactile mechanical stimulation of the hindlimbs. Ventral bilateral thoracic spinal cord lesions that spared only the dorsal funiculus and portions of the dorsolateral funiculus (three cats) significantly reduced orienting responses to all mechanical hindlimb stimuli and reduced, but did not eliminate, movement and interrupt responses to noxious thermal hindlimb stimuli. Response latency was unaffected. Food-induced response supression persisted although lumbar spinal cord concentrations of serotonin (5HT) and norepinephrine (NE) were markedly reduced. A bilateral lesion of the dorsal funiculi and dorsal portions of the dorsolateral funiculi (one cat) also reduced nocifensive responsiveness, but only the NE concentration in lumbar spinal cord was reduced significantly relative to a matched cervical sample. In contrast, deep bilateral lesions of the dorsolateral funiculi (two cats) produced an increase in the probability of movement and interrupt responses without affecting either response latency or food-induced response supression. Lumbar spinal cord concentrations of NE and, in one cat, 5HT were reduced. We conclude that (1) the dorsal and ventral spinal funiculi are each sufficient to initiate and necessary to maintain normal supraspinally organized nocifensive behavior in the cat; (2) descending monoaminergic pathways are not necessary for the phasic modulation of these responses; and (3) the tonic excitability, but not the phasic modulation, of these responses is determined in part by fibers in the dorsolateral funiculus.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/50039/1/902700412_ftp.pd

Somatic stimuli, spinal pathways, and size of cutaneous fibers influencing unit activity in the medial medulary reticular formation

Analysis of unit activity in the medial medullary reticular formation of unanesthetized, decerebrate and decereballate cats showed that: (i) 66% of the units responding to natural somatic stimuli were influenced only by firm pinching of skin folds or by heavy pressure over some part of their receptive fields; (ii) 86% of the units responding to electrical stimulation of cutaneous nerves required volleys containing both A and A-delta fibers for maximum response; (iii) unit responses to nerve volleys including A-delta fibers could be maintained above 70% of maximum levels even though anodal polarization of the nerve had produced differential block of the larger A fibers; (iv) somatically evoked potentials and unit discharge could be markedly reduced or eliminated by section of the ventolateral spinal cord quadrants, but high cervical section of dorsal and dorsolateral fascicles had no effect; and (v) evoked potentials and unit discharge could be elicited by stimulation in the dorsomedial mid-brain tegmentum and by stimulation of the caudal, but not rostral, cut end of the dorsal columns sectioned between C1 and C2. These findings suggest that a neural population in the medial medullary reticular formation is part of a system subserving responses to noxious stimuli.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/32901/1/0000281.pd

The introduction and current status of the multidimensional model of pain neurobiology

Conceptual models are useful because they guide our practical actions related to whatever is represented by the model; this includes research that reveals the limitations of these actions and the potential for their improvement. These statements apply to many aspects of daily life and especially to pain as a challenge for both clinical practice specifically and neurobiology generally. In the first half of the 20th century, our conceptual model of pain, to the extent that it existed at all, was based on evidence supporting the proposition that pain emerged from activity within a very spatially limited set of central nervous system (CNS) structures located within the cerebral cortex and it's oligosynaptic connections with the thalamus. This CNS activity was strongly associated with the activation of physiologically distinct and specialized somatovisceral afferent fibers. All, or nearly all, aspects of the pain experience were thought to arise from, and be modified by, changes in that localized CNS activity. There was no compelling and widely accepted reason to consider an alternative model. However, neurophysiological, neuroanatomical, behavioral, and clinical evidence emerging in the late mid-20th century prompted a reconsideration of the prevailing model of pain neurobiology. Based on this new evidence and the perceived limitations of the prevailing model, pain could then be reasonably conceived as a multidimensional experience arising from the conjoint activation of physiologically and anatomically distinct but interacting CNS structures each separately mediating sensory discriminative, affective, and cognitive aspects of pain. This brief historical review describes the intellectual climate at the time this multidimensional model was proposed, the dispositions for resisting or accepting it, and concludes with a comment on the current status of the model as a fusion of distributed activations that create a unified perception of pain

Observations on anodal polarization of cutaneous nerve

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Intraspinal latency, cutaneous fiber composition, and afferent control of the dorsal root reflex in cat

The intraspinal delay, fiber composition, and excitability of the cutaneous dorsal root reflex (DRR) was studied in pentobarbital-anesthetized cats.A maximal cutaneous DRR is elicited by a volley of cutaneous fibers with conduction velocities above the A-delta range. The addition of A-delta and C fibers does not increase DRR amplitude or duration; nor does an isolated A-delta or C fiber volley, delivered during anodal polarization block of the larger fibers, elicit a DRR. Collision experiments reveal that the initial phase of the cutaneous DRR recorded from nerves is composed of activity in large myelinated fibers; the later phase is due to active A-delta fibers. Thus, the observations reveal that A-delta fibers carry, but do not elicit, the DRR.A collision technique shows that the minimum delay for the inter-fiber interaction producing the DRR may be as short as 1.5 msec, a value compatible with DRR mediation by one interneuron.Prolonged DRR depression follows mechanical stimulation of the skin and single shock or repetitive electrical stimulation of the A-alpha cutaneous afferents capable of DRR excitation; neither large (A-alpha) fiber volleys below DRR thresh-old nor isolated A-delta volleys depress the DRR. In the case of cutaneous nerves, this depression affects unconditioned nerves, but the effects of dorsal rootlet tetany are restricted to DRRs elicited by or recorded from the conditioned rootlet.The results are summarized in a model in which A-alpha cutaneous afferent fibers activate interneuronal systems mediating DRR excitation and depression.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/33990/1/0000262.pd

Rewarding and aversive brain stimulation opposite effects on medial thalamic units

Most of the neurons recorded from rat medial thalamus are inhibited by medial forebrain bundle and excited by reticular stimuli delivered at frequencies of 20-60 Hz. These opposite neural responses in single units parallel the opposite behavioral and motivational properties of the brain stimuli and may play a role in integrating reward and pain mechanisms.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/33959/1/0000229.pd

Excitatory connection from lateral hypothalamic self-stimulation sites to escape sites in medullary reticular formation

Behavioral tests show that noncontingent stimulation of self-stimulation sites in the lateral hypothalamus increases escape and avoidance from central or peripheral stimuli. The present study investigated the possibility that this phenomenon was mediated by an excitatory connection from the lateral hypothalamus to neurons in aversive regions of the brainstem. Most of the 24 rats participated in two phases of the experiment: unit recording under anesthesia; and behavioral tests with intracranial stimulation in the waking state. Recordings of 120 units were obtained from the n. gigantocellularis reticularis (NGC) since stimulation of this region in the awake rat consistently elicited escape behavior. Unit responses could be divided into two catagories: 61% responded to deep pinch or foot shock (or both) but not to light brushing of the hair; and 39% responded to light brushing of the hair or were not responsive. Stimulation of behaviorally confirmed self-stimulation sites in lateral hypothalamus evoked short-latency (2 and 4 msec) excitation of 88% of the NGC units in the first category and only 15% in the second. Nearly all hypothalamic sites not eliciting self-stimulation also failed to excite NGC units. The excitatory hypothalamic-bulboreticular connection may serve to increase the excitability of a nociceptive system during self-stimulation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/32736/1/0000105.pd

A microprocessor device for the real-time detection of synchronized alpha and spindle activity in the EEG

A microprocessor based device is described which permits the real-time detection of synchronized EEG activity within the frequency range of the alpha rhythm or sleep spindles. This device offers a reliable, inexpensive method for EEG analysis according to flexible, user selectable parameters. It can be used either on-line or off-line and provides information as to the occurrence and duration of alpha-spindle EEG activity.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/26254/1/0000335.pd