Biomedical subjects

R F Hellon

Publications and source records attributed to R F Hellon.

At least 19 recordsLinked to original sources

PubMed1987

Hypothalamic control of nocireceptive and other neurons in the marginal layer of the dorsal horn of the medulla (trigeminal nucleus caudalis) in the rat.

The effect of electrical stimulation of the preoptic area of the hypothalamus on the discharge of neurones in the marginal layer (lamina I) of the trigeminal nucleus caudalis was studied in the anaesthetised rat. There was a powerful suppression of the discharge evoked by noxious thermal stimuli in 49/49 specific nociceptor driven (nocireceptive) neurones. The inhibitory effect increased with graded increases in the intensity of preoptic stimulation. Stimulation, however, produced only a small reduction in the discharge of 14/17 cold receptive neurones. Thresholds for producing suppression of cold receptive neurones were generally higher than those for nocireceptive neurones. There was no effect on the activity of 12/12 low threshold mechanoreceptive neurones. The inhibitory action generated on the activity of nocireceptive neurones was reduced by electrolytic lesions in the nucleus raphe magnus (NRM) or the nucleus paragigantocellularis lateralis (PGCL) or the dorsolateral and ventrolateral periaqueductal gray matter (PAG). Lesions made in the ventral or dorsal aspect of PAG were, however, ineffective in reducing the suppression. It is suggested that the powerful descending inhibitory control of nociceptive transmission in the trigeminal nucleus caudalis is one of the neuronal mechanisms mediating analgesia from the preoptic area of the hypothalamus.

Action Potentials↗

PubMed1986

Medial hypothalamic stimulation produces analgesia to facial heating in unrestrained rats.

Gradual heating of the face in unrestrained conscious rats produced a behavioural response at a mean threshold temperature of 41.9 degrees C (S.E.M. +/- 0.02, 174 tests). This temperature did not change with tests repeated at 5-min intervals over one hour. During stimulation of the preoptic area of the hypothalamus the response temperature was consistently raised by about 3 degrees C but returned to the control level within 5 min.

Analgesia↗

PubMed1985

Naloxone does not influence a pyrogen fever in rabbits.

Rabbits were made febrile by an intravenous injection of homologous endogenous pyrogen (Interleukin 1). When naloxone (0.1 mg/kg i.v.) followed by 0.06 mg (kg X hr)-1 infusion) was given at the same time as the pyrogen, the resulting fever was indistinguishable from that following pyrogen alone. It appears unlikely that opioid receptors which are blocked by naloxone play an important part in the fever process.

Animals↗

PubMed1985

Transmission of low temperature information in the rat trigeminal system.

Recordings have been made from cold-receptive neurons in trigeminal nucleus caudalis to define the lower receptive field temperatures at which the neurons become silent. Most cells were found to become silent at 0 degrees C, but a few were still active at skin temperatures of -5 degrees C.

Animals↗

PubMed1985

Sensory processing in a thermal afferent pathway.

Extracellular recordings were made from cold-receptive afferent fibers in the trigeminal ganglion of rats anesthetized with halothane. By applying a standardized series of steady or changing temperatures to the receptive fields, we recorded the static and dynamic responses of the afferents. Comparable recordings were made from neurons in the marginal layer of the caudal trigeminal nucleus onto which the cold fibers synapse. The static and dynamic responses of the afferent fibers were reproduced faithfully by the second-order neurons, but at a much higher level of activity. Ganglionectomy silenced the second-order cells. Their continuous high level of activity appears to depend on the tonic input from the afferent fibers and not on any intrinsic circuits in the medulla.

Afferent Pathways↗

PubMed1984

Inhibition of brain protein synthesis suppresses the release of prostaglandin E2 in febrile rabbits.

In rabbits the third cerebral ventricle was perfused using a push-pull cannula. Prostaglandin E2 concentration in the perfusate was measured by radioimmunoassay. Prostaglandin concentration rose during fever induced by an intraventricular injection of endogenous pyrogen. Both fever and the increased prostaglandin concentration were suppressed by the intraventricular injection of 100 micrograms of the protein synthesis inhibitor, anisomycin. A possible interpretation of the findings is that anisomycin inhibits the formation of phospholipase A2. If this is true, the implication is that phospholipase A2 has a rapid turnover in brain.

Animals↗

PubMed1983

Intraventricular injections of drugs which inhibit phospholipase A2 suppress fever in rabbits.

Injection of two chemically dissimilar inhibitors of phospholipase A2 (mepacrine and parabromophenacylbromide) into the cerebral ventricles of rabbits inhibited the febrile response to endogenous pyrogen given by the same route. 2. The same doses of the inhibitors given intravenously did not affect the febrile response to endogenous pyrogen given into the ventricles, indicating that their action was central. 3. When given intraventricularly the inhibitors did not affect the maintenance of core temperature in a cold environment, indicating that they did not impair thermoregulatory ability. 4. The inhibitors had no effect on the temperature rise following intraventricular injection of arachidonic acid. 5. These observations are compatible with the proposition that one or more metabolic products of arachidonic acid other than prostaglandin are involved in pyrogenesis.

Acetophenones↗

PubMed1983

Facial sensitivity to rates of temperature change: neurophysiological and psychophysical evidence from cats and humans.

The dynamic responses in a thermal afferent pathway to rates of temperature change have been studied in anaesthetized cats. Recordings were made in the caudal trigeminal nucleus from neurones with a synaptic input from facial cold receptors. Five rates of cooling and warming ranging from 0.05 degrees C/sec to 1 degree C/sec were applied to the receptive fields of the neurones. Several measures of the dynamic response were computed but the most representative was the maximum rate during cooling or the minimum rate during warming. During cooling the maximum rate increased with increasing cooling rates between 0.05 degrees C/sec and 0.25 degrees C/sec, but did not increase at faster rates. Minimum activity during warming reached near zero at rates of 0.25 degrees C/sec and faster. The total number of impulses generated during cooling or absent during warming was unrelated to rate of temperature change. The same thermal stimuli were applied to the cheeks of human subjects. They were able to sense cooling or warming changes at 0.05 degrees C/sec. They could also distinguish the faster of two cooling changes when these were slow, but not when they were fast. Warming rates could not be distinguished, except from an adapting temperature of 35 degrees C, when warm receptors would have been activated. There was good agreement between the responses of the cat neurones and the human sensations. Slow rates of cooling could be detected or distinguished. Fast rates appeared to saturate the neuronal and sensory mechanisms.

Adult↗

PubMed1982

Further observations on the suppression of fever in rabbits by intracerebral action of anisomycin.

1. Anisomycin has been given into the cerebral ventricles of rabbits. The inhibitory action of a range of doses on fever and on [14C]leucine incorporation into hypothalamic protein has been studied. 2. Fever was far less sensitive to inhibition by anisomycin than was incorporation of [14C]leucine. The dose--response curves showed a general similarity in shape, which would be compatible with the hypothesis that protein synthesis may be necessary for the production of fever. 3. A comparison was made of the effects of giving anisomycin into the cerebral ventricles 0, 30 or 60 min after the intraventricular injection of leucocyte pyrogen. Anisomycin inhibited fever to some extent even when given 60 min after leucocyte pyrogen. This suggests that if protein synthesis is involved in fever, it may continue at least into the early phase of rising temperature, but probably not to any significant extent after the plateau has been reached.

Animals↗

PubMed1982

Inhibition, by trichothecene antibiotics, of brain protein synthesis and fever in rabbits.

1. To test further the hypothesis that brain protein synthesis is necessary for fever, three structurally similar trichothecene antibiotics were injected into the cerebral ventricles of rabbits. They were 3,15-diacetoxy-12-hydroxytrichothec-9-ene (DAHT), 3,15-didesacetyl-calonectrin (DDAC) and T-2 toxin. Their actions on hypothalamic incorporation of [14C]leucine and fever were compared. 2. DDAC (60 micrograms) and T-2 toxin (10 micrograms) strongly inhibited leucine incorporation and fever. DAHT (60 micrograms) did not diminish fever and had a smaller effect upon leucine incorporation. 3. The findings strengthen considerably earlier suggestions that brain protein synthesis is an essential step in pyrogenesis.

Animals↗

PubMed1982

An analysis of a thermal afferent pathway in the rat.

1. Single unit activity has been recorded in the thalamic, hypothalamic and raphe magnus nuclei of rats anaesthetized with Urethane.2. Neurones were sought which responded to changes in scrotal skin temperature applied with a water-perfused brass thermode. All sixty-nine neurones in the thalamus and hypothalamus responded with abrupt changes in activity as the scrotum was warmed (;switching response'). The majority responded with an increase in activity from minimal to maximal firing rate as the scrotum was warmed over a range of less than 0.5 degrees C; in about 20% of the neurones the converse was observed.3. To determine whether the switching response of the thalamic and hypothalamic neurones depended upon a cortico-thalamic feed-back loop, the cortical surface was cooled to 18-20 degrees C to reversibly abolish cortical post-synaptic activity.4. Cortical cooling abolished the positive switching response of nearly all (15/19) ventrobasal thalamic neurones to scrotal warming. All eight ventrobasal thalamic neurones with negative switching responses, and all twenty-two scrotal temperature-responsive neurones in other thalamic and hypothalamic nuclei were unaffected.5. Twenty recordings were also made from scrotal temperature-responsive neurones in the nucleus raphe magnus. All possessed switching responses similar to those observed in the thalamus and hypothalamus.6. None of the scrotal temperature-responsive neurones in the nucleus raphe magnus was affected by cortical cooling. Six neurones were observed in decerebrate rats with properties apparently identical to those in intact rats.7. We conclude that the switching response of thalamic and hypothalamic scrotal temperature-responsive neurones is probably generated in the nucleus raphe magnus and passed in parallel to the thalamus and hypothalamus. In addition, thalamic neurones depend on an intact link with the cerebral cortex for the generation of their switching responses.

Afferent Pathways↗

PubMed1982

Facial thermal input in the caudal trigeminal nucleus of rats reared at 30 degrees C.

1. Rats reared from birth in air at 30 degrees C showed a decreased ability to maintain colonic temperature when exposed to 10 degrees C as compared with rats reared at 20 degrees C. This difference was not due to physical factors affecting heat loss, such as surface area or fur thickness. 2. In anaesthetized rats extracellular recordings were made in trigeminal nucleus caudalis from higher order neurones with input from facial cold and warm receptors. A systematic search on a grid pattern showed there was no difference between heat-reared and control rats in facial receptive fields or in the abundance, extent and somatotopic distribution of thermal neurones in the nucleus. In both groups almost all the neurones were excited only by facial cooling. 3. When single cold neurones were tested quantitatively by the application of controlled temperature changes to their receptive fields on the face there was no difference in the static temperature/discharge rate relationship between the two groups of rats. 4. The results suggest that the observed difference in ability to regulate body temperature is not attributable to differences in skin-temperature reception at the level of the trigeminal nucleus.

Animals↗

PubMed1981

Tooth pulp input to the spinal trigeminal nucleus: a comparison of inhibitions following segmental and raphe magnus stimulation.

In rats and cats anaesthetized with urethane a comparison was made of the inhibitory effects of raphe magnus (NRM) and segmental (facial skin) stimulation on neurones in nucleus caudalis excited by tooth pulp stimulation. The upper and lower ipsilateral incisor teeth were used in rats (176 neurones) and the corresponding canine teeth in cats (34 neurones). The recording sites were located in all layers of nucleus caudalis and in the underlying reticular formation. Both the evoked responses and the conditioning effects were similar in the two species. Both forms of conditioning inhibited about half the neurones tested but only as small proportion was influenced from both sources. NRM stimulation had almost identical effects on neurones driven from upper teeth or from lower teeth and tended to act on those cells with longer latencies. Segmental stimulation influenced the majority of shorter latency cells and produced greater inhibitions of upper tooth pulp neurones. Diffuse noxious inhibitory controls were also observed for certain neurones.

Animals↗

PubMed1981

Inhibitory controls on thermal neurones in the spinal trigeminal nucleus of cats and rats.

Although electrical stimulation of supraspinal structures and local large fibres is known to inhibit the responses of nociceptive neurones, comparable studies on thermoreceptive cells have not been made. We have studied the effects of nucleus raphe magnus (NRM) and segmental stimulation on cold and warm responsive neurones in trigeminal nucleus caudalis of both the rat and cat. All 48 neurones (46 cold and 2 warm) tested in the cat and 24 cold neurones in the rat were unaffected by the NRM at a variety of stimulation parameters. However, segmental stimulation inhibited 4/20 neurones in the cat and 11/26 cells in the rat. The results show the selectivity of the inhibition following NRM stimulation.

Animals↗

PubMed1981

Neurophysiology of temperature regulation: problems and perspectives.

The neuronal basis of thermal regulation has been intensively studied. Certain neurons in the hypothalamus and elsewhere are extremely sensitive to changes in local and/or external temperature. Recent in vitro work indicates that membrane potentials rather than synaptic events may be the basis of the local sensitivity. Other central sites outside the central nervous system are also now being recognized as sources of thermal information to the thermoregulatory system. The skin thermal input relays to the nucleus raphe magnus and probably passes from there to the hypothalamus. There is still much uncertainty about how and when the skin and deep thermal receptors provide input to the temperature controller.

Animals↗

PubMed1980

Cell responses evoked by tooth pulp stimulation above the marginal layer of the cat's trigeminal nucleus caudalis.

In cats anesthetized with urethane, all-or-nothing, synaptically evoked recordings were made from 80 separate units in the descending spinal tract of the trigeminal nerve above the left trigeminal nucleus caudalis, at depths not exceeding 50 micrometer from the surface of the medulla. The units were excited by the left upper (21), left lower (25), either (28), or only on simultaneous stimulation of both (six) canine tooth pulps. There was no somototopic distribution. The latency of responses ranged from 4 to 82 msec. For the group of 28 units excited by upper and lower tooth pulps, there was close matching of response latencies from the two teeth. An abrupt decrease in latency upon increasing stimulation strength ("jumping"), and a gradual increase in latency during repetitive stimulation at a frequency between 1 and 20 Hz ("drifting") was characteristic of most, but not all, responses. Units evoked by stimulation of the inferior dental or infraorbital nerves had similar characteristics. Stimulation of a tooth pulp at threshold for a particular unit was used to test the excitability of that unit after suprathreshold stimulation of the same or a different canine tooth pulp. Stimulation of the upper left canine tooth pulp was generally only facilitatory, while stimulation of the lower left canine tooth pulp was initially facilitatory and later inhibitory. Stimulation of the upper or lower right canine tooth pulps did not excite but could inhibit units excited by the left canine tooth pulps. There was a significant correlation between the frequency at which a unit would follow repetitive stimulation and the duration of the inhibition generated by the first of a pair of stimuli. Long inhibition was associated with poor frequency following.

Animals↗

PubMed1980

Excitation and inhibition of marginal layer and interstitial interneurons in cat nucleus caudalis by mechanical stimuli.

In cats anesthetized with urethane, the caudal medulla was stabilized in preparation for intracellular recording from interstitial neurons in the descending tract of the trigeminal nerve and from neurons in lamina I of nucleus caudalis. Glass micropipets (10-50 M ohms) were advanced from the surface to a maximum depth of 350 micrometer. When DC potential shifts occurred, it was found that mechanical stimuli to the face generated bursts of positive-going spikes, followed in some cases by inhibitory postsynaptic potentials (IPSPs). Subdermal electrical stimulation of the face in each receptive field almost always enabled the same neuron to be driven electrically. Recordings were classified as from primary afferent fibers or from interneurons. Primary fibers had a purely positive spike, with a latency varying by no more than 0.05 msec, and could follow stimulation at 500 Hz. The mean latency for the fibers was 1.87 +/- 0.06 msec (n=75), and their absolute refractory period was 0.42 +/- 0.02 msec (n=36). Recordings were classed as from interneurons if there was an IPSP or the latency was at least 4 msec, with a variation of latency of at lest 0.5 msec. Responses thought to be monosynaptically driven had a mean latency of 2.09 +/0 0.07 msec (n=32) and could follow pairs of stimuli at a mean minimum interval of 0.70 +/- 0.06 msec (n=20). Responses thought to be polysynaptically driven had a mean latency of 7.9 +/- 1.08 msec (n=49) and a mean interstimulus interval of 2.96 +/- 0.84 (n=20). Most responses were generated by brushing the face (n=87), some by pressure on the face (n=25), and a few by pinching the skin of the face (n=6). Interneuron responses were most commonly recorded in the first 200 micrometer of the descending tract, and this position was confirmed by the injection of pontamine sky blue and the examination of frozen sections. The recordings were thought to be from dendrites of marginal and interstitial cells or the somas of interstitial cells. The IPSPs which followed spike potentials could only follow stimuli at 10 Hz or less. The failure appeared to be at a primary afferent synapse upon an inhibitory interneuron. Collision tests between mechanically evoked and electrically evoked responses showed long-lasting inhibition of the response to electrical stimulation after collision. Presynaptic inhibition exerted on the primary afferent excitation was suggested as the explanation.

Animals↗

PubMed1980

The chill sensation in fever.

Seven men were almost totally immersed in water at a neutral temperature (34.5 degrees) and given an intravenous injection of exogenous pyrogen. Five subjects who exhibited fever and visible shivering all reported sensations of chill at the time of shivering. Two subjects who did not shiver reported neutral sensation throughout. The results indicate that reduction of skin temperature is not necessary for the chill sensation in fever. The chill must arise from some central action of pyrogen.

Adult↗