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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of electrical and chemical stimulation of the arcuate nucleus of the hypothalamus (ARH) on the tail flick latency (TFL) and paw pressure withdrawal threshold (PWT) were investigated in the lightly pentobarbital-anesthetized and acutely prepared rat. Electrical stimulation of the ARH for 20 sec at 8 Hz produced a more potent elevation of the TFL (98%) and PWT (68%) compared to when stimulation was applied to the same site at 2 Hz (41% and 25%, respectively), 32 Hz (64% and 42%) and 128 Hz (57% and 39%). An even more marked and longer attenuation of the nociceptive reflexes was observed when the ARH stimulation was extended to a period of 1 or 3 min. Microinjection of the excitant amino acid, L-glutamate (0.5 M, 0.1 mul), into the same areas of the ARH consistently elicited antinociception to an extent similar to that observed with electrical stimulation. The data indicate that 8 Hz seems to be an optimal frequency for stimulating ARH to produce an analgesic effect as tested by the two spinal nociceptive reflexes.
Pain 1990 Apr
PMID:Characterization of inhibition of spinal nociceptive reflex by stimulation of the arcuate nucleus of the hypothalamus in the pentobarbital-anesthetized rat. 197 70

Neuroendocrine and autonomic responses were assessed in chloralose-anesthetized cats after chemical stimulation of medial brain-stem regions, including those that influence nociceptive input to the medullary or spinal dorsal horn. Microinjections of L-glutamate (0.5 M, 160 nl) were directed at the following rostral and caudal raphe nuclei: the periaqueductal gray (PAG), the dorsal raphe nucleus (DR), the raphe magnus (RM), and the raphe obscurus/raphe pallidus (Ro/Rpa). Activation of DR neurons evoked a significant increase in the adrenal secretion of epinephrine (+2.6 +/- 1.1 ng/min, P less than 0.01) that returned towards prestimulus values by 6 min, whereas microinjections into other raphe nuclei had no consistent effect. Activation of Ro/Rpa neurons evoked an increase in the plasma concentration of adrenocorticotropin (ACTH, +47.9 +/- 12.3 pg/ml, P less than 0.01), whereas microinjections into other raphe nuclei did not affect ACTH. Arterial pressure increased significantly after activation of PAG (+7.5 +/- 2.1 mm Hg, P less than 0.01) or of DR (+4.8 +/- 2.0 mm Hg, P less than 0.05) neurons, whereas heart rate increased significantly (P less than 0.05) after stimulation of cells within the Ro/Rpa. Glutamate microinjections within the RM, a raphe nucleus that exerts a significant descending influence on nociceptive input to the medullary and to the spinal dorsal horns, had no consistent effect on any measured variable. No evidence was seen to suggest that chemical activation of neurons within raphe nuclei inhibited the adrenal secretion of catecholamines or inhibited the release of ACTH. The results indicated that glutamate activation of neurons within different raphe nuclei evoked non-uniform effects on neuroendocrine and autonomic function. Further, these data suggested that the neural substrate underlying the control of the adrenal secretion of catecholamines and of the release of ACTH in response to activation of raphe neurons is likely distinct from that which contributes to the descending influence on nociceptive input to the medullary and spinal dorsal horn.
Pain 1990 Jul
PMID:Comparison of the influence of rostral and caudal raphe neurons on the adrenal secretion of catecholamines and on the release of adrenocorticotropin in the cat. 197 77

Descending influences on the spinal nociceptive tail-flick (TF) reflex produced by focal electrical stimulation and glutamate microinjection in the nuclei reticularis gigantocellularis (NGC) and gigantocellularis pars alpha (NGC alpha) were examined and characterized in rats lightly anesthetized with pentobarbital. Both inhibition and facilitation of the TF reflex were produced by electrical stimulation at identical sites in the NGC/NGC alpha; glutamate microinjection only inhibited the TF reflex. The chronaxie of stimulation for inhibition of the TF reflex was 169 +/- 28 microseconds. Inhibition of the TF reflex by stimulation was produced throughout the NGC and NGC alpha; intensities of stimulation for inhibition were least in the ventral NGC and in the NGC alpha. At threshold intensities of stimulation, inhibition of the TF reflex did not outlast the period of stimulation. Facilitation of the TF reflex was produced at many of the same sites at which stimulation inhibited the TF reflex, but always at lesser intensities of stimulation (mean, 10 microA vs. 43 microA for inhibition, n = 25). Stimulation in the NGC/NGC alpha at threshold intensities for facilitation or inhibition of the TF reflex did not significantly affect blood pressure. Strength-duration characterization of electrical stimulation and microinjection of glutamate into identical sites in the NGC and NGC alpha suggest that descending inhibition of the TF reflex results from activation of cell bodies in the NGC and NGC alpha.
Pain 1990 Sep
PMID:Characterization of descending inhibition and facilitation from the nuclei reticularis gigantocellularis and gigantocellularis pars alpha in the rat. 197 61

Microinjection into the midbrain periaqueductal gray (PAG) or lateral reticular formation (LRF) of the neuronal excitant glutamate produces analgesia, and suppresses the responses of a fraction of spinal dorsal horn neurons to noxious heat applied to ventral hind paw skin. Microinjection of morphine into the PAG also produces analgesia, but has been reported to frequently facilitate, as well as to suppress or have no effect, on nociceptive spinal neurons. In anesthetized rats, we tested whether (a) glutamate microinjections into PAG or LRF, and (b) morphine microinjections into PAG, affected the isometric force of hind limb withdrawal elicited by the same noxious heat stimuli on the hind paw as used in single-unit studies of dorsal horn neurons. Glutamate (0.5 M; 0.1-0.5 microliter) microinjected at 9/12 PAG and 8/10 LRF sites suppressed the reflex, and had no effect or facilitated the reflex from the remaining sites. Morphine (5 micrograms in 0.5 microliter) microinjected at each of 10 PAG sites suppressed the reflex in a naloxone-reversible manner. Suppression usually began shortly after morphine, peaked at 20-40 min, and lasted greater than 60 min. The integrated flexion reflex thus appears to be more susceptible to chemical midbrain stimulation under these experimental conditions, compared to previous studies of single dorsal horn neurons.
Pain 1990 Oct
PMID:Suppression of a hind limb flexion withdrawal reflex by microinjection of glutamate or morphine into the periaqueductal gray in the rat. 198 May 35

In cats anesthetized with Nembutal and immobilized with Flaxedil, extracellular recordings were made from dorsal horn neurons and lamina X neurons in the lumbar spinal cord. The nociceptive responses of these neurons elicited by peripheral nerve stimulation were significantly inhibited by stimulation of the nucleus tractus solitarius (NTS) at low intensity without any noticeable cardiovascular reaction. As usual, the late response or C-response was found to be preferentially inhibited by NTS stimulation as compared with the early response or A-response. The effective current intensity for NTS stimulation-produced inhibition ranged from 80 microA to 200 microA. Stronger inhibition was induced when the stimulating site was within or in the immediate vicinity of the NTS. There was no significant difference in the efficacy of the NTS stimulation-produced inhibition of nociceptive response between dorsal horn neurons and lamina X neurons. A similar inhibitory effect was elicited by microinjection of monosodium glutamate into the NTS area. The results demonstrate that the NTS may be involved in the control of nociceptive transmission at the spinal cord level.
Pain 1990 Mar
PMID:Involvement of solitary tract nucleus in control of nociceptive transmission in cat spinal cord neurons. 215 41

The processing at the spinal cord levels of sensory information is subject to modulation by a number of local receptor systems, including opioids: alpha 2 adrenergic; and to a lesser extent serotonin, GABAB, neuropeptide Y, cholinergic, adenosine, and the NMDA-glutamate site. The functional utility of these multiple systems are only partially understood, but it appears that (a) they may act individually to alter different aspects of the nociceptive sensory message (b) they could be used synergistically to reduce the incidence of side effects by reducing the dose of agents required to yield analgesic effects, and (c) they may function variably in animals made tolerant to classes of receptor agonists.
J Pain Symptom Manage 1990 Jun
PMID:Spinal administration of receptor-selective drugs as analgesics: new horizons. 216 72

During anesthesia in mice, both common carotid arteries were tied loosely with an overhand knot suture (an occluder), while two snares (releasers) were placed in the knot so that it could be repeatedly tightened to occlude the arteries and loosened again to allow for reperfusion while the mice were conscious and unrestrained. The incidence of mortality as well as impairment of brain metabolism depended upon the length of cerebral ischemia. Cortical electroencephalogram (EEG) clearly reflected the regional ischemia as evidenced by electrical quiescence. Less mortality was observed with ischemic mice treated with dextrorphan (30 mg/kg p.o.). On day 1 (24 hr after ischemia), there were impairments in complex motor coordination, multichoice swim performance, and step-through or thermal pain-motivated avoidance responses. Thereafter, the battery of tests progressively improved. This improvement depended on the period of resumption of cerebral blood flow; the 7-day, postischemic lapse significantly reduced the deficit observed. Reduction in the degree of habituation of exploratory activity was also clearly observed following ischemic insult. Dextrorphan (1-30 mg/kg i.p.) given to ischemic mice was effective in the habituation and step-through-type passive avoidance test paradigms. In conclusion, 1) the decline in cognition as observed with ischemic mice is due to the temporal and reversible derangement of their neuronal networks; 2) excessively released glutamate is probably of major pathogenic importance in the consequences of cerebral ischemia based on the positive results of the N-methyl-D-aspartate receptor antagonist, dextrorphan; 3) the simple technique could be useful in elucidating the pathophysiologic mechanisms of ischemically elicited derangement of the cerebral organization; and 4) the model could be used to assess the efficiency of drugs with high clinical predictivity.
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PMID:Cerebral ischemia model with conscious mice. Involvement of NMDA receptor activation and derangement of learning and memory ability. 216 22

Glycine is an important inhibitory transmitter in the brainstem and spinal cord. In the trigeminal subnucleus caudalis (medullary dorsal horn) and in the spinal dorsal horn (the relaying centres for processing pain and sensory information), glycine inhibits the glutamate-evoked depolarization and depresses firing of neurons. The binding of glycine to its receptor produces a large increase in Cl- conductance, which causes membrane hyperpolarization. The selectivity and gating properties of glycine receptor channels have been well characterized; the glycine receptor molecules have also been purified. The amino-acid sequence, deduced from complementary DNA clones encoding one of the peptides (the 48K subunit), shows significant homology with gamma-aminobutyric acid A (GABAA) and nicotinic acetylcholine receptor subunits, suggesting that glycine receptors may belong to a superfamily of chemically gated channel proteins. However, very little is known about the modulation of glycine receptor channels. We have investigated the regulation of strychnine-sensitive glycine receptor channels by cyclic AMP-dependent protein kinase in neurons isolated from spinal trigeminal nucleus of rat and report here that the protein kinase A dramatically increased the glycine-induced Cl- currents by increasing the probability of the channel openings. GS protein, which is sensitive to cholera toxin, was involved in the modulation.
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PMID:Modulation of glycine receptor chloride channels by cAMP-dependent protein kinase in spinal trigeminal neurons. 217 40

To better understand and treat painful conditions, one needs to identify the cause, discover the source, and develop knowledge of peripheral and central pain transmission; headaches are no exception. The development of appropriate animal models is important. Accordingly, we have reviewed the anatomy, neurochemistry, electrophysiology, and pharmacology of the trigeminovascular system in experimental animals and emphasized whenever possible the relevance of this final common pathway to migraine, cluster, and other headache syndromes in humans. For example, based on recent anatomic dissections, the pericarotid cavernous sinus plexus was suggested as an important focus to investigate cluster headache pathophysiology. This plexus is an anatomic point of convergence for the nerves giving rise to the signs of sympathetic and parasympathetic activity and sensory symptoms that develop in cluster patients. As in other nociceptive systems, trigeminovascular axons assume at least two important roles. One concerns the transmission of nociceptive information. Electrophysiologic evidence supports the trigeminal nucleus caudalis as an important site for the convergence of visceral (vessel) and somatic (forehead) inputs to mediate the referral of vascular pain to superficial tissues. A second important role concerns the initiation of local increases in blood flow and enhanced protein permeability (sterile inflammation) via the axonal release of vasoactive neuropeptides. Plasma extravasation develops within the dura mater following trigeminal stimulation. Extravasation can be blocked by the administration of ergot alkaloids or sumatriptan, a new serotonin-like agonist, and a prejunctional (neuronal) mechanism of action for these drugs (such as blockade of release) was suggested based on experimental evidence. Whether vasoconstriction also relates to the therapeutic efficacy remains to be determined. As in other organ systems, real or threatened tissue injury provides an important stimulus for depolarizing sensory fibers. The stimulus may come from external conditions such as reduced blood flow or hypoglycemia. The brain may also possess intrinsic neuronal mechanisms by which nociceptors may be synthesized (e.g., glutamate-induced neurotoxicity, seizures). Molecules of relevance include bradykinin, prostaglandins, leukotrienes, and potassium. Experimental evidence was presented demonstrating that the trigeminal nerve mediates hyperemia within cortical gray matter by axon-reflex like mechanisms. An important role for this nerve was established during the hyperemic period of recirculation after ischemia or during severe hypertension above the limits of autoregulation.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Basic mechanisms in vascular headache. 217 82

The present work reviews neurochemical, physiological and behavioral data recorded from the attacked mouse and integrates them into a model of coping mechanisms during social conflict. More specifically, the possible relationships between systems of pain, memory and defense are presented, with special emphasis on the role of endogenous opioid peptides (EOPs). In recipients of attack, decreased beta-endorphin-like immunoreactivity and changes in opiate and benzodiazepine binding characteristics are found in structures of the brain defensive system. EOPs mediate the social conflict-induced increase of dopamine synthesis in the periaqueductal grey and frontal cortex. Social conflict analgesia in attacked mice is under the control of central opioid and nonopioid (e.g., benzodiazepine, glutamate) mechanisms, and is modified by experience (e.g., long-term analgesic reaction; tolerance). EOPs and pain-inhibitory mechanisms participate in the organization of behavioral defense, recuperative behavior and the memory of attack experience. The data are considered in relation to the perceptual-defensive-recuperative model of fear and pain, forwarded by Bolles and Fanselow.
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PMID:An ethological model for the study of activation and interaction of pain, memory and defensive systems in the attacked mouse. Role of endogenous opioids. 228 85


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