Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0344307 (analgesia)
 28,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neuropharmacological studies have been conducted on the venom of V. russelli on experimental animals. The venom was found to produce alteration in general behaviour pattern, reduction in spontaneous motility, hypothermia, potentiation of pentobarbitone hypnosis, analgesia, reduction in exploratory behaviour pattern, muscle relaxant action, and suppression of aggressive behaviour. The venom caused a significant increase in brain GABA content in mice. The observations are suggestive of a potent CNS-depressant action of V. russelli venom.
 ...
PMID:Neuropharmacological studies on the venom of Vipera russelli. 181 34

The present study examined patterns of analgesia by intracerebroventricular (i.c.v.) or intrathecal (i.t.) administration of the serotonin 5-HT3 receptor agonist, 2-methylserotonin (1-100 micrograms) against acute thermal, mechanical or formalin-induced chemo-inflammatory pain in male rats. Neither i.c.v. or i.t. 2-methylserotonin produced motoric, sedative or respiratory effects. I.c.v. 2-methylserotonin was not analgesic at any dose in the pain assays employed. I.t. 2-methylserotonin produced dose-related analgesia in the formalin test with significant effects at 20-100 micrograms doses. In contrast, only the 100 micrograms dose of 2-methylserotonin produced analgesia against thermal pain, and analgesia was not observed at any dose in the mechanical pain test. The effects of 2-methylserotonin (100 micrograms) in the formalin test were attenuated by pretreatment (10 micrograms i.t.) with the 5-HT3 receptor antagonist MDL-72222, opioid antagonist naloxone or GABA antagonist bicuculline; the 5-HT2-receptor antagonist ketanserin or 5-HT1 receptor antagonist mianserin did not affect 2-methylserotonin-induced analgesia. In the thermal test, i.t. pretreatment with MDL-72222, ketanserin, naloxone or bicuculline, but not mianserin, reduced analgesic effects of 2-methylserotonin (100 micrograms i.t.). These findings suggest that spinal 5-HT3, opioid and GABA receptor systems interact to mediate acute chemo-inflammatory pain, and implicate the interaction of these systems with 5-HT2 receptor substrates in analgesia against acute thermal nociception.
 ...
PMID:Analgesic profile of centrally administered 2-methylserotonin against acute pain in rats. 195 80

Although 5-HT is clearly involved in spinal analgesia, its mode of action remains obscure, perhaps because it has multiple and often opposing effects mediated by its multiple receptor subtypes. This investigation uses selective agonists and antagonists directed at the most recently defined class of 5-HT receptors (5-HT3 receptors) in behavioral and electrophysiological studies of nociception in the spinal cord of rodents. The results demonstrate uniformly inhibitory effects of a selective 5-HT3 agonist on responses to noxious stimuli. Intrathecally administered 2-methyl 5-HT produced dose-dependent antinociception in the tail-flick test and inhibited behaviors elicited by intrathecally administered agonists for excitatory amino acid and neurokinin receptors, namely NMDA and substance P (SP). All 20 dorsal horn neurons we examined, which projected to the brain and responded to both noxious stimuli and NMDA, were inhibited in a current-related manner by this 5-HT3 agonist applied iontophoretically. Both the behavioral and electrophysiological effects were blocked not only by the 5-HT3 antagonists zacopride and ICS 205-930, but also by antagonists to the inhibitory amino acid GABA. Therefore, 5-HT via an action at 5-HT3 receptors may evoked release of GABA, which may in turn inhibit nociceptive transmission at a site postsynaptic to terminals of primary afferent fibers. If the descending serotonergic analgesic system in humans operates similarly, understanding it may enable the development of new nonopioid, nonaddictive analgesics.
 ...
PMID:Spinal 5-HT3 receptor-mediated antinociception: possible release of GABA. 206 67

The purpose of this study was to explore possible neural connections between the nucleus accumbens and amygdala involved in analgesia. The latency of the escape response elicited by radiant heat applied on snout of the rabbit was taken as an index for nociception. It was found that: (1) the analgesic effect elicited by intra-accumbens injection of morphine was attenuated dose-dependently by intra-amygdala administration of opioid antagonist naloxone, or antisera against met-enkephalin (ME) or beta-endorphin (beta-EP), suggesting the involvement of ME and beta-EP in the accumbens-amygdala connection; (2) the analgesia produced by intra-amygdaloid injection of morphine was not affected by naloxone administered to nucleus accumbens, suggesting a one-way connection between the two nuclei; (3) the analgesia of intra-accumbens injection of morphine was significantly attenuated by muscimol, the GABA receptor agonist, and enhanced by bicuculline methochloride, the GABA receptor antagonist injected into the same site where morphine was administered. The results suggest that the analgesic effect of morphine administered to the nucleus accumbens is mediated by the suppression of the GABAergic inhibitory neurons located within the nucleus.
 ...
PMID:[The neural pathway from nucleus accumbens to amygdala in morphine analgesia of the rabbit]. 208 73

The aim of this paper is to investigate the corticofugal modulation of nucleus periaqueductal gray (PAG) after electroacupuncture by topical administration of GABA on frontal cortex. Experiments were carried out on restrained rabbits immobilized with gallamine. Electrical stimulation of the n. suralis was used as the noxious stimulation. Single unit activities of PAG neurons were record with glass microelectrodes extracellularly. "Zusanli" and "Huantiao" points were stimulated by the electroacupuncture bilaterally. GABA was applied topically by means of 3 x 3 mm2 filter paper and placed on the frontal cortex. It was shown that the responses of most PAG neurons evoked by noxious stimulation were inhibited after simple electroacupuncture. On the contrary, the acupuncture effect on PAG neurons was abolished when GABA was administered on frontal cortex. However, the effect of saline control resembled that of simple acupuncture. This result suggested that the corticofugal modulation from frontal cortex may play a role in acupuncture analgesia.
 ...
PMID:[Effect of changing the functional state of frontal cortex by GABA on the acupuncture effect of PAG neurons]. 212 90

Injection of GABA into the midbrain periaqueductal gray (PAG) activates medullary neurons that are involved in pain inhibition and potentiates morphine-induced analgesia. These observations suggest that GABAergic mechanisms in the PAG may modulate the descending pain inhibitory system that arises from this structure. In the present study, the effects of GABA and GABA antagonists on membrane properties and baseline activity of PAG neurons were examined using both in vitro and in vivo preparations. Application of bicuculline methiodide (BICM), at a dose that blocked the response to GABA, potently increased the baseline firing rate in 53% of cells recorded in vitro and 74% of cells recorded in the intact preparation. Application of BICM often yielded multiple or burst spiking episodes in both preparations. In 69% of cells the effect of BICM was diminished or totally abolished when the slice was perfused with high-magnesium, calcium-free, physiological saline solution. Intracellular recordings revealed that bicuculline caused depolarization of the membrane (70% of cells), increased the firing frequency (94% of cells) and increased the frequency of excitatory postsynaptic potentials (18% of cells). The effect of bicuculline on membrane resistance was not pronounced and in 64% of neurons it did not cause any measurable change in the resting membrane resistance. PAG neurons responsive to GABA and its antagonists were observed in all regions of the PAG. However, the highest number of neurons that responded to GABA and its antgonists was found in the medial and medioventral parts of the PAG. These results indicate that PAG may contain a tonically active GABAergic network that operates, at least in part, through GABAA receptors. This GABAergic system may modulate activity in descending pain inhibitory pathways emanating from PAG.
 ...
PMID:The effect of GABA and its antagonists on midbrain periaqueductal gray neurons in the rat. 230 65

It appears that complete analgesia for labor using epidural and subarachnoid opiates alone, with a minimum of side effects, remains an unfulfilled goal. However, the combination of extremely small doses of local anesthetics and opiate drugs seems to provide excellent analgesia with a minimum of side effects. This concept of combined opiates and local anesthetics corresponds to that of modern "balanced" general anesthesia, in which small amounts of several drugs are used to provide excellent anesthesia with a minimum of the side effects seen with large doses of any single drug. In my opinion, this "balanced" regional anesthesia holds great promise for the future, especially with the discovery of new drugs that produce spinal analgesia through a variety of mechanisms. These drugs include catecholamines, clonidine, GABA agonists, substance P antagonists, prostaglandin synthetase inhibitors, and many other drugs capable of altering neural transmission in such a way that analgesia results. Obviously, labor analgesia is one area in which these combinations will be explored extensively, and the next few years should be very exciting ones.
 ...
PMID:Continuous infusions of local anesthetics and narcotics for epidural analgesia in the management of labor. 240 85

The effect of GABA agonists, namely gamma aminobutyric acid, muscimol, sodium valproate and baclofen was studied on radiant heat-induced nociception in mice. All of the drugs, with the exception of sodium valproate, enhanced the reaction time to radiant heat as effect per se. Concomitant administration of any of these agents with morphine showed a potentiation of morphine-induced analgesia. The GABA antagonists bicuculline and picrotoxin failed to reverse the antinociceptive effect; paradoxically both these agents showed antinociceptive effect per se and also enhanced the response due to morphine.
 ...
PMID:GABAergic agents-induced antinociceptive effect in mice. 251 84

The influence of intraventricular injection of GABA on electrical activities of PEN and PIN in nucleus parafascicularis of the thalamus of rats was studied. The results showed that GABA could significantly inhibit the electrical discharges of PEN and increase the electrical discharges of PIN. So it was believed that intraventricularly injected GABA could antagonize or partly antagonize the excitatory action of noxious stimuli and might thus produce analgesia.
 ...
PMID:[The influence of GABA injected into cerebral ventricle on electrical activities of pain-excitation neurons and pain-inhibition neurons in nucleus parafascicularis of the thalamus of rats]. 251 22

The putative involvement of GABAA and GABAB receptors in various behavioral and physiological effects is summarized in Table III. A division of function among the two types of GABA receptors appears to exist. GABAA receptors mediate feeding, cardiovascular regulation, anxiolytic effects, and anticonvulsive activity. GABAB receptors, on the other hand, are involved in analgesia, cardiovascular regulation, and depression. Although there is some overlap and shared functions among the receptor types, it is evident that GABAA and GABAB receptors have different behavioral and physiological profiles. Feeding, anticonvulsive activity and anxiety, for example, primarily involve GABAA receptors. Analgesia and depression, on the other hand, are GABAB effects. In those cases where GABAA and GABAB receptors mediate similar functions (e.g. cardiovascular regulation), they do so by affecting different transmitter systems and cellular mechanisms. It is proposed, therefore, that GABAA and GABAB receptors differ not only at the cellular level, but that they also have different functions in the mammalian central nervous system. The association of different subtypes of a receptor with different functions and mechanisms of action is not unique to the GABA system. D1 and D2 receptors in the dopamine system, for example, also exhibit some separation of function as do the mu, delta and kappa types of opiate receptors. Different subtypes of neurotransmitter receptors, therefore, appear to be a general organizing principle used by the brain to transduce chemical signals into different functional responses. A better understanding of the exact processes through which cellular signals are transformed into functional responses is a goal of future research.
 ...
PMID:GABA receptors: are cellular differences reflected in function? 255 81


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>