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Query: UMLS:C0344307 (analgesia)
 28,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

After suffering some setbacks since its introduction in 1967, stimulation of the spinal and peripheral nervous systems has undergone rapid development in the last ten years. Based on principles enunciated in the Gate Control Hypothesis that was published in 1968, stimulation-produced analgesia [SPA] has been subjected to intensive laboratory and clinical investigation. Historically, most new clinical ideas in medicine have tended to follow a three-tiered course. Initial enthusiasm gives way to a reappraisal of the treatment or modality as side-effects or unanticipated problems arise. The last and third phase proceeds at a more measured pace as the treatment is refined by experience. This review is divided into three parts as it traces the progress of spinal cord stimulation [SCS] and peripheral nerve stimulation [PNS]. The review commences with a discussion of the theory of SCS and PNS, and is followed by early reports during which it became apparent that the modality is essentially only effective in the treatment of neuropathic pain. The last section describes the modern experience including efficacy in specific types of pain and concludes with recent accomplishments that dramatize the relief of pain which can be achieved in nonoperable peripheral vascular disease or myocardial ischemia. Over the years, a search for those transmitters that might be influenced by spinal cord stimulation focused on somatostatin, cholecystokinin (CCK), vasoactive intestinal polypeptide (VIP), neurotensin and other amines, although only substance "P" was implicated. More recently, in animal studies, evidence that GABA-ergic systems are affected may explain the frequent successful suppression of allodynia that follows spinal cord stimulation. During the past eight years, much attention has been directed to studies that use a chronic neuropathic pain model. While PNS held significant promise as a pain relieving modality, early electrode systems and their surgical implantation yielded variable results due to evolving technical and surgical skills. These results dramatically reduced the continued development of PNS, which then gave way to a preoccupation with SCS. Modern development of SCS with outcome studies, particularly in relation to failed back surgery syndrome [FBSS] and the outcome of peripheral nerve surgery for chronic regional pain syndromes, has earned both modalities a place in the ongoing management of patients with intractable neuropathic pain. The last section, dealing with pain of peripheral vascular and myocardial ischemia, is perhaps one of the more exciting developments in stimulation produced analgesia and as the papers discussed demonstrate, can provide a level of analgesia and efficacy that is unattainable by other treatment modalities. SCS and PNS has an important role to play in the management of conditions that are otherwise refractory to conservative or other conventional management.
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PMID:Stimulation of the central and peripheral nervous system for the control of pain. 901 59

Social conflict between mice produces analgesia in the attacked mouse. Both the magnitude and type (opioid or nonopioid) of this analgesia have been related to attack intensity and strain of mouse. In the present study low intensity social conflict (7 bites) did not produce analgesia, whereas high intensity - 30 and 60 bites - interactions produced, respectively, short-lasting (5 min) and very short-lasting (1 min) analgesia in Swiss albino mice, when compared with nonaggressive interaction (0 bite). The 30 bites aggressive interaction induced analgesia (AIIA) was not affected by IP injection of either naloxone (5.0 and 7.5 mg/kg) or diazepam (0.5, 1.0, 2.0 and 4.0 mg/kg). However, this attack-induced analgesia was reduced after IP administration of the 5-HT1A agonists, gepirone (0.3 and 3.0 mg/kg) and BAY R 1531 (0.01 mg/kg). These results indicate that the analgesia induced by 30 bites social conflict in Swiss albino mice does not involve opioid and GABA-benzodiazepine (GABA-BZD) mechanisms. In addition, they suggest that high-intensity social conflict activates serotonergic pain modulatory systems that act through 5-HT1A receptors.
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PMID:High intensity social conflict in the Swiss albino mouse induces analgesia modulated by 5-HT1A receptors. 907 86

The present review summarises the main actions of racemic ketamine and ketamine enantiomers on central nervous system receptors. The primary CNS action of ketamine appears to be a non-competitive block of N-methyl-D-aspartate receptors. Although numerous other receptors (e.g., GABA, nicotinic acetylcholine, opiate, voltage-operated channels) have been reported to interact with ketamine, their role in inducing dissociative anaesthesia is still under discussion. In humans, characteristic electroencephalographic (EEG) changes after administration of ketamine are dose-dependent increases in delta, theta, and beta power. In equipotent doses S-(+)-ketamine induces similar EEG changes. However, in comparison to racemic ketamine and S-(+)-ketamine, R-(-)-ketamine does not suppress the EEG to the same extent. Former studies suggested that ketamine is a proconvulsive agent; however, recent studies have demonstrated anticonvulsive and even neuroprotective properties. In humans, low-dose ketamine has no influence on early cortical peaks of somatosensory evoked potentials (SEP). Larger doses induce increases in SEP amplitude while latencies are unchanged. Recent data indicate that analgesia induced by low-dose ketamine may be quantitated by specific pain-related SEP. Significant reductions of pain-induced cortical potentials may be correlated with subjective pain ratings. Brain-stem auditory evoked potentials (AEP) are not influenced by ketamine. Interestingly, in contrast to many other anaesthetics, middle-latency AEP were not altered by racemic and S-(+)-ketamine. This observation may indicate insufficient suppression of auditory stimulus processing during ketamine anaesthesia. Motor evoked responses to transcranial electrical or magnetic stimulation in humans are not markedly suppressed by ketamine.
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PMID:[Effects of ketamine on CNS-function]. 916 74

Activation of supraspinal gamma-aminobutyric acid-A (GABAA) receptors is known to result in antagonism of opioid analgesia. Since benzodiazepines enhance the action of GABA at GABAA receptors, we hypothesized that administration of these agents for preoperative sedation might antagonize the analgesic effects of opioids administered postoperatively. If so, then administration of the benzodiazepine antagonist flumazenil should enhance postoperative morphine analgesia. In a double-blind, placebo-controlled study of patients who received a preoperatively administered benzodiazepine (diazepam) for sedation and a postoperatively administered opioid (morphine) for analgesia, we investigated opioid-benzodiazepine interactions affecting postoperative dental pain. We found that flumazenil significantly enhanced morphine analgesia consistent with the hypothesis that the preoperatively administered benzodiazepine exerts an ongoing antianalgesic effect. In addition, we followed these patients over the first and second postoperative days to determine if there were differences between the drug groups in post-discharge pain, analgesic consumption, or side-effects. Participants receiving flumazenil reported significantly less post-discharge nausea and used significantly less ibuprofen. Since post-discharge pain levels were not significantly different, these results suggest that the patients receiving flumazenil required less analgesic medication to achieve a comparable level of pain control. In summary, our results indicate that the benzodiazepine antagonist flumazenil enhances morphine analgesia and decreases post-discharge side-effects as well as post-discharge need for analgesic medication.
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PMID:Benzodiazepine mediated antagonism of opioid analgesia. 920 Jan 70

The spinal cord contains endogenous substances (such as cholecystokinin, FMRFamide, etc.) that can block the analgesic effects of opiates. Anti-opiate actions have been most commonly studied by exogenous administration of receptor agonists and receptor antagonists of these substances. However, we have recently demonstrated that anti-analgesia can be brought under environmental control through Pavlovian conditioning. Whereas analgesia can be conditioned to signals for danger, anti-analgesia can be conditioned to signals for safety. Using this paradigm, we have previously demonstrated that conditioned anti-analgesia can reverse a variety of opiate analgesic states, including those produced by conditioned danger signals, systemic morphine, and intrathecal mu- and delta-opiate receptor agonists. These data raise the question of the generality of anti-analgesia actions. The present series of experiments examined the ability of conditioned anti-analgesia to affect non-opiate analgesic states induced by spinal delivery of GABA(A), GABA(B), 5HT2 + 5HT1, and 5HT3 receptor agonists. While conditioned anti-analgesia had no effect on GABA(A) or 5HT2 + 5HT1 non-opiate analgesias, conditioned anti-analgesia completely blocked GABA(B) and 5HT3 non-opiate analgesias. These findings clearly demonstrate that conditioned anti-analgesia can powerfully modulate non-opiate as well as opiate analgesias and bring into question whether putative anti-opiate neuroactive substances may have broader actions than previously suggested.
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PMID:Reversal of spinal cord non-opiate analgesia by conditioned anti-analgesia in the rat. 923 66

1. The involvement of GABA(B) receptors and opioid mechanisms in homotaurine-induced analgesia has been investigated in current models of nociception by using a GABA(B) receptor antagonist, morphine, and naloxone. CGP 35348 (50-200 mg/kg IP), a highly selective GABA(B) antagonist, was administered prior to carrying out a dose-response curve of homotaurine (22.6-445 mg/kg IP) antinociceptive effect in the abdominal constriction (mice) and tail flick (rats) tests. 2. The tail flick test was performed in animals pretreated with morphine (0.5 mg/kg SC) and naloxone (1 mg/kg), 15 min before amino acid. Animals treated with saline 10 ml/kg (mice) or 1.25 ml/kg (rats) were included as control for the vehicle used. 3. CGP 35348 antagonized the antinociceptive effect of homotaurine in both tests. The range of doses affected by the interaction depended on the test assayed, but it was coincident for the main part of the dose-response curve. 4. A subanalgesic dose of morphine potentiated the antinociceptive effect of lower doses of homotaurine in the tail flick test. Naloxone pretreatment inhibited the antinociceptive effect of homotaurine. 5. These data imply that GABA(B) receptor subpopulations and opiate mechanisms are involved in the antinociceptive effect of homotaurine. Because functional relationships have been found between GABAergic and opiate systems in analgesic effects, an interaction of the two mechanisms may be operating in the effects described for homotaurine.
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PMID:GABA(B) receptors and opioid mechanisms involved in homotaurine-induced analgesia. 951 95

Activation of GABA(B) receptors produces analgesia in acute and chronic pain models. Data indicate that a possible mechanism for this effect is a GABA(B) receptor-induced blockade of neurokinin-1 (NK-1) receptor gene expression in the spinal cord. While much more potent GABA(B) receptor agonists (CGP 44532) have been developed, there is no information on their antinociceptive properties or their ability to influence NK-1 receptors. To address these issues, rats were treated with baclofen or CGP 44532 and tested for sedation, ataxia, and pain-related behaviors in a chronic pain model (formalin hindpaw injection). In a separate group of experiments the analgesic response to a single dose of CGP 44532 was tested prior, and subsequent to, its chronic administration. The results indicate that CGP 44532 is a substantially more potent analgesic than baclofen. In addition, after chronic administration baclofen was no longer capable of inducing analgesia or of inhibiting the increased expression of NK-1R mRNA and CGP 44532 was still fully effective in both regards. The results suggest that GABA(B) agonists could be clinically useful analgesics.
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PMID:Regulation of neurokinin-1 receptor expression by GABA(B) receptor agonists. 958 30

The fact that centrally acting analgesics have abuse potential commensurate with their analgesic activity raises the question of whether these effects are related. The abuse potential of drugs depends on their ability to produce reinforcing effects, which are mediated by a neural system that includes the ventral tegmental dopamine cells and their connections with the ventral striatum. Morphine and amphetamine are both powerful analgesics and have high abuse potential. Their analgesic and reinforcing effects are mediated by similar receptors, similar sites of action, and overlapping neural substrates. These coincidences suggest that reinforcers may produce analgesia by transforming the aversive affective state evoked by pain into a more positive affective state. The implications of this hypothesis and its relation to other known mechanisms of analgesia are discussed. The hypothesis predicts that drugs with reinforcing effects should produce analgesia. A survey of drugs acting through 21 classes of receptors reveals that in 13 classes there is evidence for both analgesic and reinforcing effects that are approximately equipotent. The GABA(A) agonists were found to be the only drugs with confirmed abuse potential that lack analgesic activity. The interpretation of this and several other anomalous cases is discussed.
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PMID:Analgesia and abuse potential: an accidental association or a common substrate? 958 60

The aim of the original study [S.B. Bausch, C. Chavkin, Vicia villosa agglutinin labels a subset of neurons coexpressing both the mu opioid receptor and parvalbumin in the developing rat subiculum, Dev. Brain Res., 97, 1996, 169-177] [3] was to develop a method for identifying a subset of mu opioid receptor-expressing interneurons in the rat subiculum for electrophysiological studies. Previous studies had shown that a subset of parvalbumin-positive neurons in the rat subiculum could be labeled with the lectin, Vicia villosa agglutinin (VVA) [C.T. Drake, K.A. Mulligan, T.L. Wimpey, A. Hendrickson, C. Chavkin, Characterization of Vicia villosa agglutinin-labeled GABAergic neurons in the hippocampal formation and in acutely dissociated hippocampus, Brain Res., 554, 1991, 176-185] [11], and that mu opioid receptor immunoreactivity (-IR) and parvalbumin-IR were colocalized in a subset of neurons in the hippocampus and dentate gyrus [S.B. Bausch, C. Chavkin, Colocalization of mu and delta opioid receptors with GABA, parvalbumin and a G-protein-coupled inwardly rectifying potassium channel in the rodent brain, Analgesia, 1, 1995, 282-285] [2]. We hypothesized that a subset of mu opioid receptor-expressing neurons in the subiculum also would express the calcium binding protein, parvalbumin, and could be labeled with VVA. Labeling of live neurons with VVA [11] then could be used to identify these neurons. This protocol was designed to triple-label neurons expressing the mu opioid receptor, parvalbumin and the carbohydrate group, N-acetylgalactosamine (which binds VVA [S.E. Tollefsen, R. Kornfeld, The B4 lectin from Vicia villosa seeds interacts with N-acetylgalactosamine residues alpha-linked to serine or threonine residues in cell surface glycoproteins, J. Biol. Chem., 258, 1983, 5172-5176][M.P. Woodward, W.W. Young, R.A. Bloodgood, Detection of monoclonal antibodies specific for carbohydrate epitopes using periodate oxidation, J. Immunol. Methods, 78, 1985, 143-153] [25, 29]). VVA labeling and immunocytochemistry with an affinity-purified anti-mu opioid receptor antibody [S.B. Bausch, T.A. Patterson, M.U. Ehrengruber, H.A. Lester, N. Davidson, C. Chavkin, Colocalization of mu opioid receptors with GIRK1 potassium channels in rat brain: an immunocytochemical study, Recept. Channels, 3, 1995, 221-241] [4] and an anti-parvalbumin antibody [M.R. Celio, W. Baier, L. Scharer, P.A. de Viragh, C. Gerday, Monoclonal antibodies directed against the calcium binding protein parvalbumin, Cell Calcium, 9, 1988, 81-86] [8] were used to accomplish this goal. Immunofluorescence was used as the detection method; visualization was accomplished with three fluorophores with different excitation/emission spectra and a one laser confocal microscope. This protocol can be modified easily to triple-label neurons for other carbohydrate groups and proteins.
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PMID:A method for triple fluorescence labeling with Vicia villosa agglutinin, an anti-parvalbumin antibody and an anti-G-protein-coupled receptor antibody. 963 Jun 78

Vaginocervical stimulation (VS) releases multiple neurotransmitters into superfusates of the spinal cord; these can stimulate both nociceptive (e.g., glutamate, and glycine acting at the NMDA site), and antinociceptive (e.g., GABA, norepinephrine, 5-HT, and glycine acting at the strychnine-sensitive receptor) systems. Although the balance between these two opposing systems can determine the nature, magnitude, and duration of the response to VS, the characteristic prevailing response to VS is analgesia. We hypothesized that by counteracting the nociceptive component of this system, the magnitude and duration of the response to VS would be augmented. In the present study, the NMDA receptor antagonist AP5 [10 microg injected intrathecally (i.t.)] significantly increased the magnitude and duration of the analgesia (measured as tail flick latency to radiant heat) produced by VS (200 g force). At several time points the analgesic effect of AP5 combined with VS was greater than the sum of the effects of AP5 and VS separately, suggesting that they act synergistically. We propose that AP5 potentiates the analgesic effect of VS by two mechanisms: (a) antagonizing the putative pain-producing action of glutamate and glycine acting jointly at the NMDA receptor, and consequently, (b) permitting the unimpeded expression of the analgesic action of inhibitory neurotransmitters released by VS (e.g., glycine at the strychnine-sensitive receptor, and GABA).
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PMID:Analgesic synergism between AP5 (an NMDA receptor antagonist) and vaginocervical stimulation in the rat. 971 6


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