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

Swimming-induced analgesia was studied in 4 strains of mice differing in central opiate receptor density: C57BL/6By (C57), BALB/cBy (BALB/c), CXBK and CXBH. The degree of 'swim analgesia' significantly differed among strains in the order CXBH greater than BALB/c = C57 greater than CXBK. This order positively correlates with known differences in opiate receptor density in these strains. Naloxone reversed the analgesic effect of swimming in CXBH, C57 and BALB/c, but was ineffective in opiate receptor-deficient CXBK mice. These results suggest that genetic differences in central opiate receptor density influence the analgesic response to stressful stimuli.
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PMID:Strain differences in the magnitude of swimming-induced analgesia in mice correlate with brain opiate receptor concentration. 283 28

Anatomical and electrophysiological studies have demonstrated that enkephalinergic, noradrenergic, and serotonergic pathways projecting from the brain-stem to the dorsal horn inhibit nociceptive transmission at the spinal level. Previous attempts to delineate interactions between opioids, norepinephrine (NE), and serotonin (5-HT) in the production of spinal analgesia have produced conflicting results. The present study determined the effect of intrathecal (i.t.) pretreatment with opioid, NE, and 5-HT antagonists upon i.t. monoamine- and morphine-induced antinociception as assessed with the rat tail-flick model. Naloxone, at a dose which antagonized i.t. morphine analgesia, had no effect upon i.t. NE but inhibited i.t. 5-HT antinociception. Corynanthine or yohimbine (NE antagonists) reduced analgesia elicited by i.t. NE but not morphine, while pretreatment with methysergide or ketanserin (5-HT antagonists) attenuated both i.t. 5-HT- and morphine-induced antinociception. These results suggest that (1) an opioid link mediates spinal 5-HT but not NE antinociception, and (2) 5-HT but not NE participates in spinal morphine analgesia.
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PMID:Opioid-monoamine interactions in spinal antinociception: evidence for serotonin but not norepinephrine reciprocity. 284 36

Flupirtine, a novel analgesic agent, was tested on nociceptive activity in neurones of the dorsomedial part of the ventral nucleus of the thalamus (VDM) and ascending axons of the spinal cord of rats under urethane anaesthesia. Activity was elicited by supramaximal stimulation of the sural nerve. Flupirtine injected i.v. dose dependently reduced nociceptive activity in the thalamus and ascending axons. The ED50 of flupirtine in depressing the thalamic response was 1.9 mg/kg, and the ED50 in depressing the C fibre-evoked response in ascending axons was 18 mg/kg. Naloxone reduced the depression of the nociceptive response evoked in the thalamus when applied before but not when applied after flupirtine. The results indicate that flupirtine produces analgesia by spinal inhibition of nociceptive impulse transmission from afferent nerve fibres to neurones sending their axons to the brain and, in addition, by supraspinal inhibition of nociceptive impulse transmission to the thalamus. Opioid mechanisms could be involved in these effects.
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PMID:Flupirtine depresses nociceptive activity evoked in rat thalamus. 284 54

The antinociceptive effects of morphine-6-glucuronide (M6G) were examined in two animal models of pain, the tail immersion test (reflex withdrawal to noxious heat) and the formalin test (behavioral response to minor tissue injury). In the tail immersion test, M6G produced an increase in withdrawal latency that rose rapidly between 0.01 and 0.025 ug ICV or 1 and 2 mg/kg SC. A further increase occurred at doses greater than 0.2 ug ICV or 4 mg/kg SC and was associated with marked catalepsy and cyanosis. Naloxone, 0.1 mg/kg SC, shifted the lower component of the dose-effect relation by a factor of 24. In the formalin test, 0.01 ug M6G ICV produced hyperalgesia, while between 0.05 and 0.2 ug ICV, antinociception increased rapidly without toxicity. The dose effect relations for hyperalgesia and antinociception were shifted to the right by factors of 20- and 3-fold, respectively. By comparison, ICV morphine was 60 (formalin test) to 145-200 (tail immersion test) times less potent than M6G. At sub-nanomolar concentrations, M6G enhanced the binding of [3H]-etorphine, [3H]-dihydromorphine and [3H]-naloxone to rat brain membrane receptors by 20-40%. At higher concentrations, M6G displaced each ligand from binding sites, with Ki values of about 30 nM, as compared to morphine Ki values of about 3 nM. The data indicate that the in vivo and in vitro effects of M6G are complex and that M6G may play an important role in analgesia in experimental animals, and by implication, in man.
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PMID:Morphine-6-glucuronide: analgesic effects and receptor binding profile in rats. 284 67

In partially restrained alert rats and mice, the opioid mechanism of the transcranial electroanalgesia was investigated. Naloxone (0.5-2.0 mg/kg) reversibly suppressed the electroanalgesia in rats. The electroanalgesic effect in rats tolerant to morphine in doses 5-10 mg/kg, was absent. The involvement of endogenous opioid mechanisms in electroanalgesia was confirmed by enhancing of the analgesia with D-phenylalanine (350 mg/kg). The findings suggest that analgesic effect is based on transcranial electrical stimulation of opioid mechanisms. Investigation of endogenous opioid mechanisms in different antinociceptive brain structures in experimental models of transcranial electroanalgesia, is discussed.
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PMID:[The opiate mechanism of transcranial electroanalgesia in rats and mice]. 285 Sep 43

We evaluated the development of naloxone-reversible and naloxone-non-reversible analgesia induced by footshock in rats of different ages and correlated it with the concentrations of beta-endorphin and dynorphin in brain areas and the spinal cord. We observed that naloxone-non-reversible shock-induced analgesia appeared first and its appearance might be related to the early presence of high dynorphin concentrations in the spinal cord. Naloxone-reversible analgesia appeared later together with the reaching of adult concentrations of cerebral beta-endorphin.
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PMID:Naloxone-reversible and non-reversible shock-induced analgesia during development. 286 71

Opiates and opioid peptides were administered in the order of 10(-9)-10(-6) mol peripherally, and their action on pain sensitivity was investigated by the modified formalin test which has two characteristic pain responses (the first and the second phase) in the mouse hindpaw. Opioid peptides (20-500 pmol) had dose-dependent analgesia against both first and second phases, and their action ranked dynorphin greater than [D-Ala2, Met5]-enkephalinamide greater than [Met5]-enkephalin. EKC and morphine (0.4-2.5 nmol) inhibited pain response of the first phase, but produced hyperalgesia in the second phase dose-dependently. Lidocaine hydrochloride had peripheral analgesic action, but was about 500-10000 times weaker than these substances. So, these peripheral analgesic actions have a different mechanism from that of local anesthetic action. N-methyl levallorphan which is thought to be a peripherally selective narcotic antagonist reversed these peripheral analgesic actions at the first and second phases and also prevented the hyperalgesic effects of EKC and morphine at the second phase. Naloxone reversed analgesia at only the first phase. These results suggest that an analgesic mechanism by opioids may exist at the peripheral site as well. Furthermore, it is estimated that a receptor exists which is antagonized by N-methyl levallorphan but not by naloxone and that there is a system of hyperalgesia by EKC and morphine in pain modulation.
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PMID:[Peripheral analgesic actions of opioid peptides and morphine analogues]. 287 30

An acute form of "stress-analgesia" is evoked by allowing the smoke of a cigarette to envelope the nostrils of unanaesthetized rabbits. The response consists of an immediate and generalized arrest of spontaneous movements, including respiration and expiration, reduced muscular tone, and unresponsiveness to pinching. This motor "paralysis" is accompanied by a profound bradycardia. Attempts have been made to identify the neurotransmitters involved in "the smoke reflex" by the intervention of antagonists and psychopharmaca. The bradycardia was selectively blocked by atropine, leaving the somatomotor inhibition unaltered. All components of the response were abolished by approximately 60% by clonidine and by 40% by the tricyclic antidepressant amitriptyline, both of which are known to attenuate the release of noradrenaline as agonsits of alpha 2-adrenoceptors. Yohimbine blocked the clonidine effect. Naloxone (1-2 mg/kg), p-chlorphenylalanine and dexamethasone failed to influence the reflex response, suggesting that opiate, serotonergic and ACTH-systems do not play a critical role. The same applied to the benzodiazepine chlordiapoxide. The results suggest that this acute stress-induced analgesia is mediated via a noradrenergic system. The relationship of the smoke reflex to "the fear paralysis reflex", a possible trigger mechanism for the sudden infant death syndrome, is discussed.
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PMID:Neurotransmitters in "the smoke reflex" in rabbits. 288 36

The blood-brain barrier is capable of transporting peptides with anti-opiate (Tyr-MIF-1) and opiate (enkephalins) activity out of the central nervous system. The relationship of this transport system to the various actions of opiates remains unexplored. This study examined the relationship between the rate of transport and opiate-induced analgesia. Both restraint, a stress that provokes an opiate-mediated analgesia, and the administration of morphine (12 mg/kg, i.p.) each induced an inhibition in the rate of transport. Such inhibition exhibited specificity, since the saturable, brain to blood transport of iodide remained unaltered. However, it was possible to dissociate analgesia and inhibition of transport. The onset and peak of analgesia, as measured by tail-flick latency induced by morphine, preceded the onset and peak of the inhibition of transport. Naltrexone, which blocks opiate-mediated analgesia, also induced inhibition of transport without any significant effect on tail-flick latency. (-) Naloxone but not (+) naloxone also weakly inhibited transport. Deprivation of food and water, associated with analgesia possibly mediated by the opiate, beta-endorphin, which is not transported out of the brain by this system, did not alter transport. These results suggest that while inhibition of transport and analgesia may occur together, these events probably represent two separate aspects of the action of opiates, that may even be mediated by separate receptor sites or peptides in the opiate family.
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PMID:Analgesia and the blood-brain barrier transport system for Tyr-MIF-1/enkephalins: evidence for a dissociation. 289 31

The high-affinity mu-1 opioid binding site has been implicated in some opioid responses (e.g., supraspinal analgesia) but not others (e.g., respiratory depression) by comparing the actions of naloxone, a short-acting, non-selective antagonist, and naloxonazine, an irreversible and selective mu-1 antagonist. The mu-1 site has been implicated in the opioid component modulating free feeding and deprivation-induced feeding, but not glucoprivic feeding. The present study compared naloxone and naloxonazine antagonism of hyperphagia induced by morphine, ethylketocyclazocine (EKC), dynorphin and d-ala2,d-leu5-enkephalin (DADL) in rats. Morphine produced a dose-dependent (0.01-5 mg/kg) hyperphagia in mildly food-deprived rats that was blocked by naloxone (0.01-10 mg/kg). Naloxonazine (10 mg/kg) shifted the morphine hyperphagia dose-response curve to the right. These effects could not be fully accounted for by the intrinsic hypophagic properties of these antagonists. EKC produced a dose-dependent (0.5-5 mg/kg) hyperphagia which was blocked by naloxone (10 mg/kg) only at low effective EKC doses. Naloxonazine (10 mg/kg) failed to affect EKC hyperphagia. Naloxone, but not naloxonazine also blocked dynorphin and DADL hyperphagia. These results indicate that feeding induced by opiate and opioid agonists are differentially mediated by the mu-1 and other opioid binding sites; these data contrast with the modulation by the mu-1 site of the supraspinal analgesia induced by each of these agonists.
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PMID:Differential sensitivity of opioid-induced feeding to naloxone and naloxonazine. 289 39


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