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

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

After the administration of 11 mg/kg of sodium nitrite (NO of the generating drug) the motor disinhibition and increase in the myogram amplitude were observed in reaction of rabbits to non-reinforced flashes at the background of continuous light which served as a conditioned inhibitory signal (CIS). The disinhibition appeared within 1-1.5 h from he moment of NO administration and continued during the whole recording period (4 h). Under the NO dose of 5.5 mg/kg only the tendency was observed to motor disinhibition after the CIS presentation. The results obtained can be possibly explained by the NO ability to inhibit the functions of the GABA-ergic receptors, since it is known that elaboration of the internal inhibition is accompanied by an enhancement of the inhibitory hyperpolarizing processes realized with participation of the GABA-ergic transmitter system. Under the action on NO both in the small and doubled doses the myogram amplitude did not increase in response to combined presentation of the light flashes with pain reinforcement, in contrast to the repeated presentations of these paired stimuli in the control experiments. This phenomenon is probably determined by the inhibitory influence of NO on the NMDA receptors.
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PMID:[The effect of sodium nitrite on the realization of defensive and inhibitory conditioned reflexes]. 918 27

1. The aim of this review is to consider the relative roles of inhibitory and excitatory amino acid receptor-mediated events in the processes leading to pain transmission in the spinal cord. 2. Emphasis will be on the roles of the inhibitory and excitatory amino acids, GABA and glutamate, and how the relative balance between activity in these systems appears to determine the level of pain transmission. 3. The N-methyl-D-aspartate (NMDA) receptor for glutamate has been implicated in the generation and maintenance of central (spinal) states of hypersensitivity. It has been shown that activation of this receptor underlies wind-up, whereby the level of transmission of noxious messages is potentiated. Antagonists at this receptor-channel complex prevent or block enhanced (hyperalgesic) pain states induced by tissue damage, inflammation, nerve damage and ischemia. 4. Information concerning amplification systems in the spinal cord, such as the NMDA receptor, is a step toward understanding why and how a painful response is not always matched to the stimulus. Such events have parallels with other plastic events such as long-term potentiation (LTP) in the hippocampus. 5. However, the roles of inhibitory transmitter systems can also change insofar as opioid, adenosine and GABA transmission in the spinal cord can vary in different pain states. 6. Changes in GABA systems have been well-documented and discussion will center on whether this has clinical implications. 7. In addition to behavioral and electrophysiological approaches to the pharmacology of pain the current status of the use of markers of early onset genes such as c-fos, as monitors of activity, will be discussed. 8. Hyperalgesia would appear to be balanced by inhibitions during inflammatory conditions but not in neuropathic states, pains due to nerve damage. In the latter case, events reminiscent of LTP may predominate, whereas they are held in check by inhibitions under conditions of inflammation.
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PMID:The pharmacology of excitatory and inhibitory amino acid-mediated events in the transmission and modulation of pain in the spinal cord. 918 94

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.
Pain 1997 May
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.
Pain 1997 Jul
PMID:Reversal of spinal cord non-opiate analgesia by conditioned anti-analgesia in the rat. 923 66

An important reaction in rodent models of persistent pain is for the animal to turn and bite/lick the source of discomfort (autotomy). Comparatively little is known about the supraspinal pathways which mediate this reaction. Since autotomy requires co-ordinated control of the head and mouth, it is possible that basal ganglia output via the superior colliculus may be involved; previously this projection has been implicated in the control of orienting and oral behaviour. The purpose of the present study was therefore, to test whether the striato-nigro-tectal projection plays a significant role in oral responses elicited by subcutaneous injections of formalin. Behavioural output from this system is normally associated with the release of collicular projection neurons from tonic inhibitory input from substantia nigra pars reticulata. Therefore, in the present study normal disinhibitory signals from the basal ganglia were blocked by injecting the GABA agonist muscimol into different regions of the rat superior colliculus. c-Fos immunohistochemistry was used routinely to provide regional estimates of the suppressive effects of muscimol on neuronal activity. Biting and licking directed to the site of a subcutaneous injection of formalin (50 microliters of 4%) into the hind-paw were suppressed in a dose-related manner by bilateral microinjections of muscimol into the lateral superior colliculus (10-50 ng; 0.5 microliter/side); injections into the medial superior colliculus had little effect. Bilateral injections of muscimol 20 ng into lateral colliculus caused formalin-treated animals to re-direct their attention and activity from lower to upper regions of space. Muscimol injected unilaterally into lateral superior colliculus elicited ipsilateral turning irrespective of which hind-paw was injected with formalin. Oral behaviour was blocked when the muscimol and formalin injections were contralaterally opposed; this was also true for formalin injections into the front foot. Interestingly, when formalin was injected into the perioral region, injections of muscimol into the lateral superior colliculus had no effect on the ability of animals to make appropriate contralaterally directed head and body movements to facilitate localization of the injected area with either front- or hind-paw. These findings suggest that basal ganglia output via the lateral superior colliculus is critical for responses to noxious stimuli which entail the mouth moving to and acting on the foot, but not when the foot is the active agent applied to the mouth. The data also suggest that pain produces a spatially non-specific facilitation of units throughout collicular maps, which can be converted into a spatially inappropriate signal by locally suppressing parts of the map with the muscimol.
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PMID:Microinjections of muscimol into lateral superior colliculus disrupt orienting and oral movements in the formalin model of pain. 933 Mar 60

Neuropathic pain may be effectively relieved by electric stimulation of the spinal cord (SCS). However, the underlying mechanisms for the ensuing pain relief are poorly understood. In a rat model of neuropathy displaying hypersensitivity to innocuous tactile stimuli, (allodynia), we have earlier demonstrated that SCS may normalise withdrawal response thresholds. In the present study, using microdialysis, it is shown that SCS induces a decreased release of the dorsal horn excitatory amino acids (EAA), glutamate and aspartate, concomitant with an increase of the GABA release. Local perfusion with a GABA(B)-receptor antagonist in the dorsal horn transiently abolishes the SCS-induced suppression of the EAA release. Thus, the effect of SCS on neuropathic pain and allodynia may be due to an activation of local GABAergic mechanisms inhibiting the EAA release which is chronically elevated in such conditions.
Pain 1997 Oct
PMID:Spinal cord stimulation attenuates augmented dorsal horn release of excitatory amino acids in mononeuropathy via a GABAergic mechanism. 941 60

In this study, we examined the modulation by acetylcholine of electrocorticographical (ECoG) ictal events and spontaneous pain-like behaviors following cortical application of the GABA(A) antagonist picrotoxin in the awake rat. Distilled water as vehicle, the cholinomimetic substance eserine, and the general muscarinic antagonist atropine were microinjected 10 min before the second microinjection of 2 microg picrotoxin into the hind paw region of the somatomotor cortex (SmI). Under these conditions, we observed that eserine (physostigmine, 1 microg, 10 microg, and 20 microg) did not consistently modify the number of the picrotoxin-induced ECoG spikes and bursts, but instead produced a massive enhancement of the number of hind paw licks compared with vehicle at 10 microg and, to a lesser extent, the number of the stereotyped "turn-in" and "neglected" paws following picrotoxin. In contrast, atropine (1 microg, 10 microg, and 20 microg) increased the number of the picrotoxin-induced spikes and bursts at 10 microg and, at all doses, decreased the number of the picrotoxin-induced pain-like symptoms. Statistically significant changes for the number of paw lifts, licks, and "turn-in" paws were observed only with 10 microg. These results tend to show that epilepsy and pain are not strictly related to each other and also emphasize the cortex as a target for interactions between GABA and acetylcholine relative to "central" pain.
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PMID:Cholinergic modulation of the picrotoxin-induced electrocorticographical events and behavioral "pain-like" symptoms at somatomotor cortical level in the rat. 943 3

To understand the biological basis of anxiety, the following psychological aspects are discussed: The difference between "trait" and "state" anxiety, types of anxiety as related to knowledge about causes and consequences, anxiety as a chronological process involving coping strategies and different levels of responses. The lack of specificity is physiological indicators of anxiety is demonstrated by experiments based on electrodermal and cardiovascular responses. Among hormones, special emphasis is placed on the constellation between catecholamines and cortisol as being relevant for anxiety research. It is emphasized that configurations of hormone parameters may be more relevant predictors for anxiety than single response values, and the study of postoperative catecholamine and cortisol responses is used for demonstrating differences between patients in a high and low preoperative state of anxiety. Differences are observed only on the emotional and pain response levels, but not in physiological parameters. The neurophysiological model representing central nervous system substrates for anxiety is the behavioural inhibitory system described in the theory by Gray [17], and the most relevant transmitters noradrenaline, serotonin, and the GABA-system are discussed with regard to their relevance for anxiety in animal studies, in studies using provocation tests with pharmacological substances, and in clinical studies with anti-anxiety drugs. Experimental anxiety research in psychology is frequently characterised by significant interactions between many mediators of responses, in particular the type of stressor, the level of trait anxiety and other personality variables, and the type of substances used. It is concluded that stressors as well as drugs frequently do not specifically induce anxiety but may nonspecifically affect general arousal and may only be operating in certain groups and certain levels of stress intensity.
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PMID:[Explanatory models of anxiety from the viewpoint of biopsychology and pharmacopsychology]. 944 74

Microinjection of baclofen, a gamma-aminobutyric acidB (GABA[B]) receptor agonist, in the nucleus raphe magnus (NRM) or nucleus reticularis gigantocellularis pars alpha (NGCpalpha) of the rat produces antinociception at doses of 0.1-1.0 ng and hyperalgesia at doses of 30-150 ng in the tail-flick test. The antinociception is proposed to result from disinhibition of spinally-projecting neurons in this region that contain serotonin. The hyperalgesia is proposed to result either from inhibition of these neurons or from disinhibition of a serotonergic pain facilitatory pathway that also originates in this area of the ventromedial medulla. To determine the involvement of bulbospinal serotonergic pathways in the biphasic effects of baclofen, rats were pretreated intrathecally with either 30 microg of methysergide or saline. Ten minutes later, either saline, 0.5 ng or 150 ng of baclofen was microinjected in the NRM and NGCpalpha, and alterations in nociceptive threshold were assessed by the tail-flick and hot-plate tests. Intrathecal pretreatment with methysergide prevented the increase in tail-flick latency produced by 0.5 ng of baclofen, but did not prevent the decrease in tail-flick latency produced by 150 ng of baclofen. Neither dose of baclofen altered hot-plate latency and this lack of effect was unchanged by methysergide. These data support the idea that the antinociceptive effect of low doses of baclofen in the tail-flick test is mediated by disinhibition of a bulbospinal serotonergic projection and release of serotonin in the spinal cord. These data also suggest that the hyperalgesia produced by high doses of baclofen does not result from disinhibition of a serotonergic pain facilitatory pathway, but rather from direct inhibition of tonically-active pain inhibitory neurons in the NRM and NGCpalpha.
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PMID:Intrathecal methysergide antagonizes the antinociception, but not the hyperalgesia produced by microinjection of baclofen in the ventromedial medulla of the rat. 957 93


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