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

Abstract

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 (greater than or equal to 47 degrees 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 suppression 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 suppression. 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.

Descending control of nociception: Specificity, recruitment and plasticity

“…Thus, for example, it has long been recognized that the pain threshold is elevated when hungry animals are given access to food 14, 15. Moreover, there appears to be an equilibrium between responding to noxious inputs and the need to maintain energy balance.…”

Shifting the Balance: How Top-Down and Bottom-Up Input Modulate Pain via the Rostral Ventromedial Medulla

“…Under basal conditions (i.e., in the absence of persistent injury or inflammation), the nociceptive threshold is measurably lower if a noxious stimulus is delivered during a period when the ON-cell population is active compared to when the OFF-cells are active ( 16 ), and inactivation of RVM can produce hyperalgesia due to loss of OFF-cell output ( 48 ). Subtle shifts in nociceptive sensitivity mediated by these normal fluctuations in ON- and OFF-cell firing likely contribute to the prioritization of pain behaviors relative to other behavioral priorities, such as feeding ( 49 , 50 ). However, factors that eliminate the OFF-cell pause, such as mu-opioid agonist administration, can entirely suppress nociceptive behavior ( 51 ).…”

“…The effect of behavioral state on pain is not limited to contexts with negative emotional valence. Feeding has been shown in several species to be accompanied by measurably reduced responses to noxious stimuli ( 49 , 50 , 75 ). This hypoalgesia is associated with reduced ON-cell activity and increased OFF-cell activity, and is eliminated by blockade of the RVM ( 75 ).…”