Brainstem influences on transmission of somatosensory information in the spinocervicothalamic pathway

The inhibition of somatosensory responses of lateral cervical nucleus neurons resulting from stimulation of the brainstem has been investigated. Single unit extracellular recordings were obtained from neurons in the lateral cervical nucleus of chloralose-anesthetized cats. Electrical stimulation of the periaqueductal gray, nucleus raphe magnus, nucleus cuneiformis, and nuclei reticularis gigantocellularis and magnocellularis was found to be very effective in inhibiting the responses of lateral cervical nucleus neurons evoked by electrical or tactile stimulation of the skin. Additional experiments were performed to determine whether the inhibitory effects were mediated in the spinal cord dorsal horn or in the lateral cervical nucleus. These experiments which examined the effect of brainstem stimulation on the responses induced by stimulation of the dorsolateral funiculus or on the antidromic latency of activation of lateral cervical nucleus neurons from thalamus, revealed that most and possibly all the inhibition could be accounted for by an action on the spinal cord. These results are consistent with other studies showing that spinocervical tract cells in the spinal cord can be inhibited by stimulation of the same brainstem regions.     

Tail-flick related activity in medullospinal neurons

The effects of midbrain electrical stimulation on the activity of tail-flick (TF) related neurons in the rostral ventromedial medulla (RVM) were studied. Neurons whose activity either decreased (off-cells) or increased (on-cells) immediately prior to TF were examined. Of 31 off- and on-cells, 26 (84%) showed increased activity during midbrain stimulation sufficient to suppress the TF. Furthermore, in 21 of these cells, the threshold for activation was identical to the threshold for TF suppression, and in the other 5 cells the threshold difference was 5 μA. This study provides evidence that off- and on-cells in the RVM mediate the antinociceptive actions of midbrain stimulation.     

Postsynaptic inhibition of cat medullary dorsal horn neurons by stimulation of nucleus raphe magnus and other brain stem sites

Sensory responses of neurons in the medullary and spinal cord dorsal horn can be inhibited by stimulation of a number of brain stem regions. These regions include the nucleus raphe magnus (NRM), the nucleus reticularis gigantocellularis (NGC), the nucleus reticularis magnocellularis (NMC), the periaqueductal gray (PAG), and the nucleus cuneiformis (CU). The purpose of this study was to determine whether or not this inhibition is mediated by postsynaptic processes. Experiments were carried out on chloralose-anesthetized cats. The responses of 29 medullary dorsal horn (trigeminal subnucleus caudalis) cells were recorded with carbon-fiber microelectrodes. Included were cells which responded to noxious stimulation (nine cells) as well as cells which responded only to nonnoxious input. The presence of postsynaptic inhibition was tested by two indirect techniques. We studied the effects of conditioning stimulation of the five regions on the latency of antidromically activated cells and also on the firing rate of neurons excited by iontophoretically applied glutamate. Conditioning stimulation was associated with a block or increased latency of antidromic activation in 15 of 18 nociceptive and nonnociceptive neurons. These effects reflect membrane hyperpolarization, presumably resulting from postsynaptic inhibition. Furthermore, conditioning stimulation of these regions inhibited the glutamate-evoked firing of all 11 cells tested, also indicating a postsynaptic type of inhibition of medullary dorsal horn cells. Thus these results indicate that at least part of the inhibition induced by stimulation of the NRM, NGC, NMC, PAG, and the CU probably results from postsynaptic inhibitory mechanisms.     

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.     

Raphe and periaqueductal gray induced suppression of non-nociceptive neuronal responses in the dorsal column nuclei and trigeminal sub-nucleus caudalis

Electrical stimulation of the feline periaqueductal gray matter and nucleus raphe magnus was found to inhibit the firing of trigeminal sub-nucleus caualis nocipeptive neurons, as has been previously reported. However, stimulation at these same sites using similar current intensities was also found to be equally effective in inhibiting the responses of non-nociceptive neurons in both nucleus caudalis and in the dorsal column nuclei.     

8-OH-DPAT-sensitive neurons in the nucleus raphe magnus modulate thermoregulatory output in rats

The nucleus raphe magnus (NRM) is purported to be a relay through which peripheral thermoafferent information is transmitted to thermointegrative centers located in the preoptic/anterior hypothalamus (POAH). Therefore, suppression of neural activity in the NRM should reduce thermoregulatory responses to peripheral thermal challenges, but not affect responses elicited by manipulation of POAH temperature. At low ambient temperatures lidocaine injections into the NRM of nonanesthetized rats resulted in decreases in POAH temperature, oxygen consumption, and electromyographic activity. At a warm ambient temperature, lidocaine injections into the NRM decreased the elevations in oxygen consumption and electromyographic activity elicited by cooling the POAH. The effects of lidocaine injections were duplicated by injection of a 5-HT(1A) agonist 8-hydroxy-dipropylaminotetralin (8-OH-DPAT) into the NRM. The effect of 8-OH-DPAT was eliminated by pre-treatment with a selective autoreceptor antagonist. These results suggest that NRM 5-HT neurons are modulating the relationship between output of thermointegrative centers and thermoregulatory effector responses rather than processing thermoafferent information.     

The rostroventromedial medulla is not involved in α2-adrenoceptor-mediated antinociception in the rat

The aim of the current study was to investigate the role of the rostroventromedial medulla (RVM) in α₂-adrenoceptor-mediated antinociception. Medetomidine or clonidine, selective α₂-adrenoceptor agonists were microinjected into the RVM in unanesthetized rats with a chronic guide cannula. The antinociceptive effects were evaluated using the tail-flick and hot-plate tests. For comparison, medetomidine was microinjected into the cerebellum or the periaqueductal gray (PAG). To study the role of medullospinal pathways, the tail-flick latencies were also measured in spinalized rats. The reversal of the antinociception induced by intracerebral microinjections of medetomidine was attempted by s.c. atipamezole, a selective α₂-adrenoceptor antagonist. The reversal of the antinociception induced by systemic administration of medetomidine was attempted by microinjections of 5% lidocaine or atipamezole into the RVM. When administered into the RVM, medetomidine produced a dose-dependent (1–30 μg) antinociception in the tail-flick and hot-plate tests, which antinociceptive effect was completely reversed by atipamezole (1 mg/kg, s.c.). Also clonidine produced a dose-dependent (3–30 μg) antinociception following microinjection into the RVM. Microinjections of medetomidine into the cerebellum or the PAG produced an identical dose-response curve in the tail-flick test as that obtained following microinjection into the RVM. In spinalized rats the antinociceptive effect (tail-flick test) induced by medetomidine microinjected into the RVM was not less effective than in intact rats. Lidocaine (5%) or atipamezole (5 μg) microinjected into the RVM did not attenuate the antinociception induced by systemically administered medetomidine (100 μg/kg, s.c.). The adapting skin temperature of the tail was increased in a nonmonotonic fashion following medetomidine. The results indicate that the RVM is not a site which is critical for the α₂-adrenergic antinociception. The antinociception following intracerebral microinjections of medetomidine into the RVM, PAG or the cerebellum in the current study can be explained by a spread of the α₂-adrenoceptor agonist into the spinal level to activate directly spinal α₂-adrenoceptors. Also, the antinociception following systemic administration of medetomidine can be explained by spinal α₂-adrenergic mechanisms. The medetomidine-induced increase of the adapting skin temperature may have attenuated the medetomidine-induced increases in the response latencies to noxious heat.     

The rostral ventromedial medulla mediates the facilitatory effect of microinjected orphanin FQ in the periaqueductal gray on spinal nociceptive transmission in rats

Single unit extracellular recordings from spinal dorsal horn neurons were obtained with glass micropipettes in pentobarbital-anesthetized rats. A total of 50 wide dynamic range (WDR) neurons were studied in 25 rats. Microinjection of orphanin FQ (OFQ, 0.1 microg/0.1 microl) (a potent endogenous ligand of the opioid receptor-like receptor (ORL-1)) into the ipsilateral ventrolateral parts of periaqueductal gray (vlPAG) significantly increased C-response and post-discharge activity in most of the WDR neurons. Pre-microinjection of lidocaine (4%) into the nucleus raphe magnus (NRM) (0.5 microl), ipsilateral nucleus reticularis gigantocellularis (NGC) (0.6 microl), or nucleus gigantocellularis pars alpha (NGCalpha) and nucleus reticularis paragigantocellularis lateralis (NPGL) (0.5 microl) markedly reduced intra-vlPAG microinjection of OFQ-induced facilitatory effects on nociceptive responses of WDR neurons. Furthermore, if the NRM and ipsilateral NGC were simultaneously pre-microinjected with lidocaine, the intra-vlPAG microinjection of OFQ-induced facilitation on nociceptive responses of WDR neurons was eliminated. Also, a similar effect was observed when all the NRM, ipsilateral NGC, NGCalpha and NPGL were blocked with lidocaine. No significant effect on nociceptive responses of WDR neurons per se was found after blocking the NRM, ipsilateral NGC, NGCalpha/NPGL, or all the NRM, ipsilateral NGC, and NGCalpha/NPGL with lidocaine. These results indicate that (1) the facilitatory effect evoked by microinjection of OFQ into the vlPAG on nociceptive responses of WDR neurons in the spinal dorsal horn is primarily mediated by the NRM and ipsilateral NGC; (2) the NRM, ipsilateral NGC, and NGCalpha/NPGL do not mediate tonic descending inhibition of the spinal dorsal horn neurons.