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

The influence on pain processing caused by destruction or stimulation of the dorsal reticular nucleus (DRt) was studied using the tail-flick and the increasing temperature hot-plate tests. Lesions of the DRt were obtained by injecting quinolinic acid (180 nmol/microliters) unilaterally or bilaterally, and nociceptive responses were evaluated by both tests. Following unilateral lesions, the tail-flick latencies and the hot-plate response temperatures were increased, values differing statistically from controls in the latter test. Bilateral lesions resulted in statistically significant increases of both tail-flick latency and hot-plate response temperature. Stimulation of the DRt was performed by injecting glutamate (100 nmol/microliters) unilaterally, which was followed 1 min later by a significant decrease in the tail-flick latency compared to saline injected controls. These results suggest that the DRt is involved in the facilitation of nociception after acute thermal noxious stimulation. This effect may be mediated through a spino-DRt-spinal loop causing a rebound of excitation in lamina I cells receiving noxious input from their own receptive field.
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PMID:The medullary dorsal reticular nucleus facilitates acute nociception in the rat. 884 10

Nociceptors belong to A delta and C afferents that are equipped in the periphery with receptors for detecting potentially damaging physical and chemical stimuli. This review summarizes experimental evidence that these receptors represented by ionic channels are also functionally expressed on the cell bodies of sensory neurones in short-term cultures. The nociceptors belong predominantly to the small and medium size DRG neurones in which algogens such as weak acids, capsaicin, bradykinin and scrotonin produce inward currents that can generate impulse activity. It seems likely that the neurones which are not sensitive to algogens but to GABA, ATP or glutamate, agents not producing pain in humans, belong to other categories of DRG neurones equipped for detecting other modalities of sensation. new techniques for physical stimulation of DRG neurones in culture may be of great help in the search for complementing the criteria for distinguishing nociceptors among other neurones in culture. It is suggested that such an in vitro model will be useful for studying cellular mechanisms of nociception.
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PMID:Can sensory neurones in culture serve as a model of nociception? 888 18

The rostral ventrolateral medulla (RVLM) is part of the vasomotor centre which controls the cardiovascular system and may therefore be critical to the genesis of postoperative hypertension. This area is probably a common site of termination of different inputs involved in the baroreflex. It contains at least two classes of neurons exhibiting spontaneous activities and projecting to sympathetic preganglionic neurons located in the intermediolateral cell-column (IML) of the spinal cord. The first class of neurons corresponds to cells with slow axonal conduction velocities (< 0.8 m s-1) and which contain immunoreactive phenylethanolamine-N-methyltransferase (CI cells); the second class, characterized by faster conduction velocities (2.5-8 m s-1), is considered as glutamatergic, although the C1 cells may also release glutamate alongside catecholamine. The purpose of the present study was to investigate the involvement of the "fast-conducting' RVLM barosensitive bulbospinal (RVLM-BB) neurons in the hypertension occurring upon emergence from halothane anaesthesia. Rats were anaesthetized with halothane, paralysed, and their lungs mechanically ventilated. Avoidable pain, distress or discomfort was consistently avoided as required by the fundamental principles of ethical animal research. Hence, all pressure points and surgical wounds, as well as tracheal tube were carefully covered or infiltrated with adequate local anaesthetic. Control experiments have been performed, allowing us to assert that hypertension accompanying halothane withdrawal was not due to suffering (see Discussion). Under halothane anaethesia, fast conducting (2.7 +/- 1.0 m s-1) RVLM-BB neurons (n = 10) exhibited a continuous discharge (8.4 +/- 7.5 Hz). Five minutes after discontinuing halothane, in increase in arterial blood pressure was recorded (AP 19 +/- 6 mmHg), which was accompanied by an increase in the unitary activities (n = 8.43 +/- 23%). Afterwards, both AP and unitary activity frequencies further increased to reach a maximum value at the end of the sequence (34 +/- 9 mmHg and 161 +/- 120% respectively, n = 10). After resumption of halothane administration, both AP and unitary activities fall down to the baseline level within 5 min (n = 10). This study shows that emergence from halothane anaesthesia reversibly induces RVLM-BB units activation, suggesting that a putative glutamatergic bulbospinal pathway may be involved in the genesis of hypertension occurring upon emergence from anaesthesia. These data may therefore contribute to better understanding of postoperative hypertension and to improve its pharmacological treatment in man.
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PMID:Increased activity of bulbospinal cardiovascular neurons in the rat rostral ventrolateral medulla upon emergence from anaesthesia. 891 58

Pain is normally evoked only by stimuli that are sufficiently intense to activate high-threshold A(delta) and C sensory fibres, which relay the signal to the spinal cord. Peripheral inflammation leads to profoundly increased pain sensitivity: noxious stimuli generate a greater response and stimuli that are normally innocuous elicit pain. Inflammation increases the sensitivity of the peripheral terminals of A(delta) and C fibres at the site of inflammation. It also increases the excitability of spinal cord neurons, which now amplify all sensory inputs including the normally innocuous tactile stimuli that are conveyed by low-threshold A(beta) fibres. This central sensitization has been attributed to the enhanced activity of C fibres, which increase the excitability of their postsynaptic targets by releasing glutamate and the neuropeptide substance P. Here we show that inflammation results in A(beta) fibres also acquiring the capacity to increase the excitability of spinal cord neurons. This is due to a phenotypic switch in a subpopulation of these fibres so that they, like C-fibres, now express substance P. A(beta) fibres thus appear to contribute to inflammatory hypersensitivity by switching their phenotype to one resembling pain fibres, thereby enhancing synaptic transmission in the spinal cord and exaggerating the central response to innocuous stimuli.
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PMID:Inflammatory pain hypersensitivity mediated by phenotypic switch in myelinated primary sensory neurons. 893 22

Pharmacological studies have implicated the spinal activation of excitatory amino acids, nitric oxide, and prostaglandins systems in the development of tactile and thermal hypersensitivity and central sensitization after peripheral inflammation. In the present study, using a chronically placed loop dialysis catheter, we examined in the unanesthetized rat the effect of carrageenan/kaolin (C/K)-induced knee joint inflammation on the time course of spinal release of several active factors including excitatory amino acids (glutamate, aspartate), citrulline (a marker of nitric oxide formation), and prostaglandin E2 (PGE2) as well as the concomitant development of tactile and thermal hypersensitivity. Infection of C/K in the knee evoked a significant release of glutamate, with an initial peak seen immediately after knee C/K injection (179 +/- 22%) and with a progressive and consistent increase over a period of 24 h (153-186%). Comparable changes in the concentration of aspartate (123-179%) were observed. Citrulline was constantly above baseline for the 24-h period (121-158%). PGE2 was significantly increased at 10 min (146 +/- 11%) with no change observed between 3-5 h. At 24 h, PGE2 was again significantly (143 +/- 18%) increased. Behaviorally, a prominent thermal and tactile allodynia developed after injection with the peak seen by 1-3 h after induction of the inflammation. This hypersensitivity state, while diminished in its intensity, persisted for the entire observation period. These data suggest that increased spinal release of excitatory amino acids (EAA), nitric oxide and/or PGE2 is involved in the maintenance of the pain state initiated by acute peripheral inflammation.
Pain 1996 Oct
PMID:Characterization of time course of spinal amino acids, citrulline and PGE2 release after carrageenan/kaolin-induced knee joint inflammation: a chronic microdialysis study. 895 28

Inflammation of the temporomandibular joint (TMJ) region evokes pain and hyperalgesia as well as causing persistent changes in the response properties of central trigeminal neurons. To determine if excitatory amino acids have a role in TMJ-induced responses, extracellular concentrations were measured in microdialysate samples from probes positioned in the spinal trigeminal nucleus (Vsp) near the transition region between subnucleus interpolaris and subnucleus caudalis (Vi/Vc) in chloralose-anesthetized rats. Injection of the selective small fiber excitant, mustard oil (20 microliters, 20% solution), into the ipsilateral TMJ region caused a transient (by 10 min) increase in glutamate (from 0.48 +/- 0.16 to 1.94 +/- 0.78 microM, P < 0.005) and aspartate (from 0.29 +/- 0.11 to 1.78 +/- 0.82 microM, P < 0.025) among sites located at the ventrolateral pole of the Vi/Vc transition region (n = 6). Samples from probes located within the ventral Vsp, but outside this Vi/Vc transition region (n = 9), did not show significant changes in amino acid concentrations. Glutamate and aspartate also increased after mustard oil injections into the contralateral TMJ region. Dialysate concentrations of serine and taurine did not change significantly after mustard oil injections. Addition of high potassium (150 mM) to the perfusate solution caused increases in glutamate and aspartate regardless of probe location. The transient and selective release of glutamate and aspartate within the Vi/Vc transition after acute irritation of the TMJ region is consistent with a proposed role for excitatory amino acids in mediating noxious sensory input from deep orofacial structures. Together with previous reports of c-fos expression, these results suggest that neurons within the ventrolateral portion of the Vi/Vc transition may serve as a relay site for the integration of sensory or reflex responses to acute inflammation of the TMJ region.
Pain 1996 Oct
PMID:Excitatory amino release within spinal trigeminal nucleus after mustard oil injection into the temporomandibular joint region of the rat. 895 41

It has been shown that an excitatory amino acid, such as glutamate and aspartate, plays an important role in the spinal nociceptive transmission. NMDA receptor is one of the receptors of excitatory amino acids. Glutamate is present in the terminals of small diameter primary afferent fibers, as well as in dorsal horn interneurons. It has been reported that NMDA receptor is not located postsynaptic to primary afferent input; rather it mediates excitation evoked by glutamate-releasing interneurons. Activation of chemosensitive afferents with chemical irritants generates a state of central sensitization in the spinal cord, and this hyperexcitability is blocked by NMDA antagonist. These data suggested that activation of chemosensitive afferents induces release of glutamate which activates NMDA receptor in dorsal horn interneurons, and that this NMDA receptor activation induces spinal sensitization. It has been suggested that this spinal sensitization plays an important role in the maintenance of neuropathic pain and hyperalgesia during inflammation. In the clinical trial, epidural administration of NMDA antagonist attenuated the level of allodynia in patients with postherpetic neuralgia. I think that spinal sensitization induced by NMDA receptor activation is the key mechanism to maintain neuropathic pain and hyperalgesia during inflammation.
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PMID:[N-methyl-D-aspartate (NMDA) receptor and pain]. 895 62

The effect of the inositol trisphosphate analog alpha-trinositol on noxious-evoked behavior, amino acid and prostaglandin E2 (PGE2) release was examined in unanesthetized rats using intrathecal microdialysis probes. Subcutaneous injection of 50 microliters 5% formalin solution produced two phases of pain-like behavior and significant elevation of glutamate, aspartate, glycine, taurine and serine during phase 1. PGE2 concentrations were increased during both phases 1 and 2. Intraperitoneal delivery of 300 mg/kg alpha-trinositol significantly suppressed both phases 1 and 2 of formalin-induced behavior and the associated elevation of amino acids and PGE2. These data demonstrate that the antinociceptive effect of alpha-trinositol corresponds to suppression of noxious-evoked release of amino acids and PGE2 from the spinal cord.
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PMID:The effect of alpha-trinositol (D-myo-inositol 1,2,6-trisphosphate) on formalin-evoked spinal amino acid and prostaglandin E2 levels. 904 42

The N-methyl-D-aspartate (NMDA) receptor for glutamate has been implicated in the generation and maintenance of central (spinal) states of hypersensitivity. Thus antagonists at this receptor-channel complex have the potential not to totally abolish pain, but to prevent or block hyperalgesic states induced by tissue damage, inflammation, nerve damage and ischaemia. Information on amplification systems in the spinal cord such as the NMDA receptor is a step towards understanding why and how a painful stimulus is not always related to the response. There are now sufficient controlled clinical studies with agents such as ketamine to believe that, in humans, NMDA mediated events are critical in pathological and/or prolonged pain states. Consequently, use of antagonists may aid the treatment of difficult clinical pains when given alone or in combination with opioids. The combinations of opioids and NMDA antagonists may be especially helpful since some NMDA mediated events can be difficult to control with opioids alone (eg. neuropathic pain states). In addition, the ability of opioids to act presynaptically on C-fibre terminals to reduce transmitter release produces synergistic inhibitions with postsynaptically acting NMDA receptor antagonists. Consequently, low dose combinations may be possible with low side-effect liability. Finally, NMDA receptor activation would appear to be responsible for the generation of nitric oxide and prostanoids which further enhance pain transmission whereas adenosine release acts to control these NMDA mediated events. Thus, further targets for the indirect control of NMDA induced activity are possible.
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PMID:NMDA receptor antagonists: interactions with opioids. 906 Oct 93

Inhibition of spinal glutamate receptors induces antinociceptive effects in numerous animal models of pain. The present study compares the effects of intrathecally administered N-methyl-D-aspartate (NMDA) and non-NMDA glutamate receptor antagonists on nociceptive responses in the tail flick test. Potency of antagonists at NMDA and alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptors was first measured by electrical assays in Xenopus oocytes expressing rat cerebral cortex poly(A)+ RNA. Subsequently, Swiss Webster mice were injected intrathecally with the antagonists and tested for antinociception. The drugs tested were: NBQX and GYKI-52466, selective AMPA receptor antagonists, ketamine, MK-801, R(+) HA-966 and ACEA-0762, selective NMDA receptor antagonists, and ACEA-1031, ACEA-1328 and ACEA-0593, NMDA receptor antagonists that also show inhibition of non-NMDA receptors. Selective NMDA receptor antagonists induced essentially no antinociceptive effects in the tail flick test. Antinociceptive activity generally correlated with inhibition of AMPA receptors. The exception was the non-competitive AMPA receptor antagonist GYKI-52466, which was unexpectedly weak. This may be due to inadequate dosing, because the compound has limited solubility, or may be due to differences in the non-NMDA receptor subtype-selectivity profile of GYKI-52466 as compared to competitive antagonists such as NBQX. Overall, our results suggest that inhibition of spinal non-NMDA receptors is the primary, and necessary, mechanism of antinociception by these drugs in the tail flick test in mice.
Pain 1997 Mar
PMID:Antinociceptive effects of NMDA and non-NMDA receptor antagonists in the tail flick test in mice. 910 7


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