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

Improved technique for recording single unit activity in awake animals

An improved system for recording the electrical activity of single neurons in the brain of awake, unanesthetized and unrestrained animals is described, including complete details of construction and use. The advantages of this new technique over earlier methods are discussed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/23365/1/0000309.pd

Effect of medial bulboreticular and raphe nuclear lesions on the excitation and modulation of supraspinal nocifensive behaviors in the cat

Six cats were trained to eat while partially restrained and while thermal pulse stimuli (43-60 [deg]C, 5 s duration) were delivered to the upper hindlimbs. Food and stimulus delivery were under programmed electronic control. The probability and latency of 3 natural, unlearned nocifensive behaviors were electronically registered: interruption of eating of of exploring for food, hindlimb movement and vocalization. Preoperatively, all cats showed significant increases in the probability of two or more behaviors as stimulus temperature increased. Each cat also showed a significant food-induced suppression of one or more of these behaviors. Thermocoagulation lesions limited to the giganto- and magnocellular fields of the medial medullary reticular formation (4 cats) produced a decrease in nocifensive responsiveness. Larger lesions within the same area but with extension into the postpyramidal raphe nuclei, resulted in increased nocifensive responsiveness (2 cats). No lesion affected response latency or the food-induced modulation of nocifensive behavior. The results support the hypothesis that supraspinally organized nocifensive responses are: (1) tonically facilitated by neural activity originating in or passing through the medial bulboreticular formation; (2) tonically suppressed by midline raphe spinal neurons; and (3) phasically modulated by suprabulbar neural mechanisms that are related to changes in behavioral state.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27712/1/0000100.pd

A contact thermal stimulator for neurobehavioral research on temperature sensation

A thermal stimulation system is described which is suitable for use in psychophysical, behavioral and neurophysiological studies of temperature sensation. Skin temperature over a restricted area can be maintained at temperatures of 30 to 60[deg]C. Heating from this initial temperature can be achieved at rates from 1.0[deg]C to 30[deg]C/second, up to a maximum temperature of 70[deg]C. Stimulus duration can be varied from 1-15 sec. Safety features are employed to avoid accidental burning of subjects. The system can be used during electrophysiological recording with no electronic interference.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/24444/1/0000718.pd

Modulation of the spontaneous and evoked discharges of ventral posterior thalamic neurons during shifts in arousal

The responses of 154 ventral posterior thalamic neurons to a variety of somatic stimuli and to electrical stimulation of the midbrain spinal lemniscus were recorded in the awake squirrel monkey during varying states of arousal. Many VP () neurons showed changes in somatosensory responsiveness which correlated with shifts in arousal. Arousal related modulation (ARM) of somatic responses were not selective for any specific stimulus modality. Most cells (N = 36) responded maximally during quiet waking with responses significantly reduced during drowsiness or periods of waking movement. Other neurons (N = 5) responded maximally during drowsiness, and gave decreased responses as the level of arousal increased. Similar changes were seen for neurons driven by spinal lemniscal (SL) stimulation. All changes in evoked responses were independent of prestimulus background discharge frequency. At least one site of ARM takes place at the level of the VP thalamus.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27164/1/0000159.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

Clonidine effects on pain evoked SII activity in humans

We investigated pain evoked activity in the human secondary sensory cortex (SII) following clonidine administration in six healthy volunteers using multi‐channel magnetoencephalography (MEG). Pain was elicited by electrical shocks applied intracutaneously to the fingertip. Subjects rated pain intensity and perceptions of tiredness and passiveness by numerical ranking scales. Each subject underwent two investigations, one week apart from each other, with clonidine doses of 1.5 or 3.0 μg/kg, administered intravenously in a random order and double‐blinded. We applied a total number of seven blocks, each consisting of 60 painful stimuli, with one adaptation block, one pre‐medication block, four post‐medication blocks and one recovery block at the end of the session. MEG data were analysed by dipole reconstruction using CURRY R (Neuroscan, Hamburg) software package. Cortical activity in the contralateral SII cortex appeared with peak latencies of 118.5 ± 10 ms. This activity was significantly reduced by clonidine, in parallel with a reduction of pain intensity and enhancement of subjective tiredness and passiveness. There was, however, no significant correlation between MEG and subjective effects. Although both clonidine doses had similar effects, the higher dose induced longer changes. Results indicate that intravenous clonidine is able to relieve pain, but the exact mechanism of clonidine at the level of the SII cortex remains unclear. It is possible that clonidine interacts with the brainstem ascending system regulating vigilance and arousal which would explain the observed decrement of pain induced activity in SII. An additional more specific analgesic action at spinal level cannot be excluded.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90357/1/j.ejpain.2005.12.003.pd

Responses of single cutaneous fibers to noxious thermal pulse stimulation of cat upper hind limb

Previous experiments have shown that cats respond to noxious thermal pulse stimulation of the upper hind limb at an average latency of 2.3 sec. To determine if C fiber afferents could mediate this response, we recorded the response latency and threshold of single fibers of cat femoral cutaneous nerve to the same stimuli used in the behavioral experiments. Of 28 C fibers tested, 10 (36%) responded to heating; 4 (17%) of 24 fibers with conduction velocities of 2.5-30 m/sec responded to heat. All fibers but one discharged within 1.0 sec of thermal pulse onset (median: 800 msec) at an average and median threshold of 46[deg]C. Thermal nociceptors with C fiber afferents could mediate the initiation of behavioral nocifensive responses to heat in the cat.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/25795/1/0000357.pd

Physiological identification of afferent fibers and postsynaptic sensory neurons in the spinal cord of the intact, awake cat

A method was developed to record from spinal cord cells in the awake, intact, partially restrained cat. Units were classified as afferent fibers or postsynaptic cells based on their ability to follow 100-Hz peripheral stimulation, the duration and configuration of the action potential waveform, and the number of spikes evoked by a single electrical pulse. These criteria are supported by independent observations of the location of the recording site, size of the receptive field, and adequate stimulus. Of 84 cutaneously activated units, 29 were classified as afferent fibers, 28 as postsynaptic cells, and 27 were not classified. No cutaneously activated unit was spontaneously active. In contract, all 28 units (7 postsynaptic and 21 not classified) responding to joint position or movement were spontaneously active (5 to 40 Hz). No unit responded to both cutaneous and proprioceptive inputs. Evidence for convergence of cutaneous input from different types of receptors was limited to five postsynaptic neurons that responded to hair movement and to stimuli applied to the skin; two of these cells responded differentially to noxious pinch. Two of 24 postsynaptic cutaneous units ceased responding to electrical cutaneous stimuli when the cat was eating. The responses of 29 primary afferent fibers were not altered by the behavior of the cat. These results suggest that, in the awake cat (i) criteria based on neuronal responsiveness and action potential waveform can be used to distinguish adequately between afferent fibers and postsynaptic cells; and (ii) there is a tonic inhibitory control, greater than in the anesthetized or spinally transected cat, that varies with behavioral state and is directed primarily at spinal neurons receiving cutaneous input.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27419/1/0000457.pd