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 layer 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 a 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.     

Response of raphe magnus neurons after acupuncture stimulation in rat

Extracellular recording was made from single cells in the nucleus raphe magnus (NRM) of Wistar albino rats. The spontaneous firing rate of these cells increased, decreased or was not altered after acupuncture stimulation. Excitatory response of the cells was obtained more often than the other ones. There were no significant differences between the effects induced by stimulation of meridian and nonmeridian points. It is suggested that only the excited neuron may participate directly in the descending analgesic system through NRM cells activated by acupuncture stimulation. Presumably, meridian point is not a specific one for activation of NRM cells in rat.     

Electrophysiological studies of a rostral projection from the nucleus raphe magnus to the hypothalamus in the rat and cat

Neurones in nucleus raphe magnus (NRM) and the adjacent reticular formation with rostral projections were identified by their antidromic responses to stimulation at periventricular forebrain sites in rats and cats. In subsequent experiments, the effects of stimulation in the midline of the ventral medulla were tested on the activities of periventricular forebrain neurones. Taken together, the results of these experiments suggest that a direct inhibitory projection may exist from NRM to ventromedial forebrain structures including the anterior hypothalamus/preoptic region in rats in addition to polysynaptic pathways which mediate both excitations and inhibitions in rats and cats.     

A pharmacological study of the modulation of neuronal and behavioural nociceptive responses in the rat trigeminal region

Electrical stimulation of the brain, particularly in the periventricular grey areas, caused long-lasting increases in behavioural escape thresholds to heating and mechanical stimuli applied to the facial region of the rat. The brain stimulation selectively suppressed responses to noxious stimuli. Responses to non-noxious stimuli, evoked by low threshold brush, were unaffected. The same animals that were studied in the behavioural tests were then anaesthetized with urethane and the inhibitory effect of the same brain stimulation was studied in single neurones recorded in the caudal trigeminal nucleus. A clear correlation (r_s = 0.63) emerged between degree of behavioural antinociception and the amount of inhibition seen in nociceptive neurones. In addition the mean duration of the inhibition (6 min) was similar to the mean duration of the antinociceptive effect (7.3 min). Other classes of non-nociceptive neurones were unaffected by the stimulation. The neurones were also studied using iontophoretically applied monoamine candidates for the inhibitory neurotransmitter, noradrenaline (NA) and 5-hydroxytryptamine (5-HT). The profile of the effects of NA most closely fitted that of the inhibitory neurotransmitter. This profile was expressed in terms of depression and excitation of different classes of neurones, and by the duration of effects. The depressant effects could be antagonized by iontophoretic idazoxan. In addition clonidine induced long-lasting depression of firing. 5-HT was more likely than NA to excite nociceptive neurones and to depress non-nociceptive neurones. Only NA consistently elevated thermal response thresholds in a similar manner to that produced by brain stimulation. These results provide some support for the hypothesis that selective descending inhibition of nociceptive responses in neurones of the rat caudal trigeminal nucleus is mediated by NA, possibly by an action at α₂-adrenoceptors.     

Evidence for peripheral, but not central modulation of trigeminal cold receptive cells in the rat

The effects of locus coeruleus (LC), periaqueductal grey (PAG) and segmental stimulation (all of which are known to inhibit convergent nociceptive cells), were tested on the activity of cold receptive cells in the trigeminal system of the rat. LC and PAG stimulation from sites which inhibited convergent nociceptive cells had no effect on cells with cold receptive input in the trigeminal nucleus caudalis. Electrical or mechanical segmental stimulation caused suppression of activity in cold receptive trigeminal nucleus neurons. Recording from the trigeminal ganglion showed this suppression to be a property of the primary afferent cold receptors themselves and therefore it is not analogous to the proposed mechanism for the segmental inhibition of convergent nociceptive neurons.     

The GABAB antagonist phaclofen inhibits the late K-dependent IPSP in cat and rat thalamic and hippocampal neurones

Phaclofen (0.5–1 mM) reversibly inhibited the late, bicuculline resistant, K⁺ dependent IPSP recorded in projection cells of the cat and rat dorsal lateral geniculate nucleus and in rat hippocampal CA1 pyramidal neurones. At the same concentrations, phaclofen reversibly blocked the K⁺ dependent, bicuculline insensitive hyperpolarization evoked by GABA and baclofen but had no effect on the GABA_A IPSP. These results represent conclusive evidence that GABA_B receptors mediate the late K⁺ dependent IPSP in cortical and subcortical neurones.     

Neurones in the medullary raphe nuclei attenuate the cardiovascular responses evoked from the dorsolateral periaqueductal grey matter

In rats anaesthetised with alphaxalone/alphadolone, electrical stimulation in the dorsolateral part of the periaqueductal grey matter (PAG; 10 s trains of 1 ms pulses at 80 Hz, 40–80 μA) evoked a pressor response accompanied by tachycardia. Both components of the response were attenuated following microinjection of 200 nl 0.1 M , -homocysteic acid into the caudal pole of the nucleus raphe magnus (NRM; n = 12) and into the nucleus raphe obscurus (NRO; n = 22) to selectively activate neuronal perikarya. Microinjection of 200 nl 165 mM NaCl into the same region (n = 15) had no effect. The attenuation of the midbrain-evoked cardiovascular responses lasted for 10–20 min and was independent of changes in resting blood pressure and heart rate. The maximum reduction in the pressor component of the midbrain-evoked responses was similar following stimulation in NRM (−35.4%) and NRO (−36.7%). However, the reduction in the midbrain-evoked tachycardia was greater following stimulation in NRM (−62.8%) compared to NRO (−27.2%). These results indicate that neurones in NRM and NRO may be involved in modulating the level of excitability of the midbrain defence area in the PAG and/or its efferent pathway.     

Preprodynorphin mRNA‐expressing neurones in the rat parabrachial nucleus: subnuclear localization, hypothalamic projections and colocalization with noxious‐evoked fos‐like immunoreactivity

The dorsal lateral subnucleus of the rat pontine parabrachial nucleus is a major target for ascending nociceptive information from the spinal cord. With in situ hybridization histochemistry, using a radiolabelled cRNA probe, we demonstrate that neurones in and near the dorsal lateral subnucleus express preprodynorphin mRNA. The cRNA probe was constructed from a PCR product amplified from rat genomic DNA. Sequencing of the PCR product revealed that it corresponded to the sequence 466–1101 of the rat preprodynorphin gene exon 4. Tract tracing experiments, using injection of cholera toxin subunit B into the hypothalamic median preoptic nucleus, showed a retrograde labelling pattern of neurones in the parabrachial nucleus that was almost identical to that of the preprodynorphin mRNA expressing neurones. Double-labelling, combining immunohistochemical detection of tracer and in situ hybridization, revealed that the retrogradely labelled neurones expressed preprodynorphin mRNA. A similar double-labelling, combining in situ hybridization with immunohistochemical detection of noxious-evoked fos following formalin injection into one hindpaw of awake animals, showed that almost all fos-immunoreactive neurones in the dorsal lateral parabrachial subnucleus also expressed preprodynorphin mRNA. Quantitative analysis suggested that the evoked fos immunoreactivity was accompanied by an increased preprodynorphin mRNA expression. The findings provide evidence that neurones in the dorsal lateral subnucleus produce dynorphin and project to the median preoptic nucleus, and that noxious stimulation in awake animals synaptically activates the dynorphinergic neurones in this subnucleus. These observations are consistent with the idea of a functional and chemical heterogeneity among different parabrachial subnuclei that serves to produce specific homeostatic responses to stimuli that changes the physiological status of the organism, including tissue damage.     

Response of nucleus raphe magnus neurons to electrical stimulation of nucleus cuneiformis: Role of acetylcholine

There is considerable evidence that cells in the ventral medulla which includes nucleus raphe magnus (NRM) and nucleus magnocellularis are involved in a descending pain inhibitory system. Anatomical studies indicate a strong projection from nucleus cuneiformis (NCF) to the ventral medulla and histochemical studies suggest that many NCF neurons are cholinergic. Therefore, we investigated the effect of NCF stimulation on NRM unit activity and explored the possible role of acetylcholine (ACh) in this interaction. Of 180 NRM neurons examined, 43% were excited and 14% were inhibited by NCF stimulation. The average latency to the peak excitatory response was about 14 ms with a range of 5-32 ms. There was a tendency for the response latencies to cluster around 5 and 14 ms. Inhibitory responses were between 10 and 65 ms in duration. The anatomical specificity of the effective stimulation site was assessed by determining the response of a given NRM neuron to stimulation of areas dorsal and ventral as well as within NCF. The most reliable and intense responses of NRM neurons was observed with electrode placements within NCF. The most effective NCF region for activating NRM neurons corresponded to that region of NCF that contains a large population of neurons that project directly to NRM as seen in the present histochemical studies. The involvement of ACh in the interaction between NCF and NRM was examined with iontophoretic application of ACh and its antagonists. Of NRM neurons that responded to ACh, 79% were excited, an effect which was blocked by scopolamine.(ABSTRACT TRUNCATED AT 250 WORDS)     

Stimulation of the subcallosal fornix excites neurones in the cat preoptic region which project to the medial basal hypothalamus and in the medial forebrain bundle

The projection of neurones in the cat preoptic region driven by stimulation of the subcallosal fornix was systematically explored. We found 19% projected to the medial basal hypothalamus (MBH) and 10% projected in the medial forebrain bundle (MFB). Neurones projecting to 3he MBH were driven more often by stimulation of the lateral aspect of the fornix than the medial aspect (P = 0.006) and these neurones were thought to lie in the medial division of the preoptic nucleus (MPNm) since they were found significantly more often in the medial 0.6 mm of the preoptic region than more laterally (P = 0.028). A reverse projection from the preoptic region in the fornix is also suggested based on the finding of 24 antidromically activated neurones inthe preoptic region following stimulation of the fornix.