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)

Experiments were performed on awake rats. The pain threshold (tail flick latency, TFL) was measured with radiant heat tail-flick method. Microinjection of thyrotropin releasing hormone (TRH 2.5 micrograms/1 microliter) into septal area can increase remarkably and last 40 min, but the analgesic effect can not be reversed by the opioid receptor blocker naloxone (NAL) into the septal area; injection 10 micrograms of morphine into unilateral septal nucleus, the pain threshold had no obvious change; the after-effect of electroacupuncture (EA) was remarkably prolonged injecting TRH (1.5 micrograms) into unilateral septal nucleus. The after-effect of EA caused by TRH could abolish by NAL. The results imply that (1) microinjection of TRH into the unilateral septal nucleus could raise TFL, intraseptal opiate receptors may not be involved in analgesic effect elicited by TRH. (2) morphine was injection into unilateral septal nucleus having no effect on TFL, suggesting that endogenous opioid peptides in the septal nuclei might not be the major role in anti-nociceptive reaction in rats. (3) Microinjection TRH into the intraseptal can obviously prolong the after-effect of EA, NAL could abolish it, indicating that endogenous opiate peptides in the septal nuclei may play a role partially in mediating EA analgesia.
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PMID:[The effects of microinjection of TRH or morphine into unilateral nucleus septum on pain threshold and electroacupuncture analgesia in rats]. 211 8

The GABAA agonist, muscimol, administered intrathecally (IT) to the spinal cord at a dose (1 microgram) that was subthreshold for affecting pain thresholds (vocalization-threshold-to-tail-shock: VTTS, and tail-flick latency: TFL) in ovariectomized, hormonally untreated rats, showed a significant increase in VTTS up to 30 min postinjection in intact females only in proestrus or estrus. This treatment produced no significant effect on TFL at any stage of the estrous cycle. IT muscimol produced a significant increase in VTTS (but not TFL) in ovariectomized rats primed with estradiol benzoate (EB) for 2 days and tested 40 hr after the second injection but had no effect in females primed with a single EB injection and tested 15 min later. By contrast, ovariectomized females primed with progesterone (P) for 15 min exhibited a significant increase in pain thresholds after IT muscimol in both the VTTS and TFL tests. When EB-primed females (2 days) received P 4 hr prior to muscimol there was no analgesia produced by IT muscimol, in contrast to EB-primed females receiving P 15 min prior to IT muscimol in which there was significant analgesia. These results suggest a mechanism for antagonistic effects of estrogen and progesterone.
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PMID:Modulation by estrogen and progesterone of the effect of muscimol on nociception in the spinal cord. 226 54

The intrathecal (IT) injection of progesterone (PROG) or three of its ring A-reduced metabolites (5 beta,3 alpha-pregnanolone, 5 alpha,3 alpha-pregnanolone, or 5 beta,3 beta-pregnanolone) did not significantly alter any of two pain thresholds (vocalization threshold to tail shock, VTTS, or tail flick latency, TFL) in ovariectomized rats when tested in a wide range of doses (2.5-250 micrograms). When combined with a subanalgesic dose of muscimol (MUSC; 1 microgram IT), PROG and its two 3 alpha-hydroxy derivatives, but not the 3 beta, caused significant analgesia in the VTTS but not in the TFL test. No clear dose-response relationships were noted in the analgesic response to the combination of the progestins and MUSC. The present results indicate that PROG, either directly or through its ring A-reduction, can modulate nociceptive information by enhancing the action of GABA agonists on GABAA receptors.
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PMID:Perispinal progestins enhance the antinociceptive effects of muscimol in the rat. 811 19

Clinical observations have suggested that cholestasis is associated with increased neurotransmission mediated by the opioid system in the central nervous system. As opiate agonists (e.g. morphine) mediate analgesia, increased opioidergic tone in cholestasis should be associated with a decreased response to pain. To test this hypothesis, the response of rats with acute cholestasis to a nociceptive stimulus was measured by the use of the tail-flick test, an extensively validated assay for measuring opiate-induced antinociception. Five and 7 days after bile-duct resection, the mean tail-flick latency was longer than before surgery (p < 0.05), whereas the corresponding means for unoperated and sham-resected controls were not significantly different from their respective baseline values. The increase in the mean tail-flick latency in the bile-duct resection group was reversed by (-)-naloxone (1 mg/kg subcutaneously), but not by its enantiomer (+)-naloxone (10 mg/kg subcutaneously) (p < 0.001). The stereoselective reversal of antinociception in cholestasis by naloxone indicates that this phenomenon is opioid-receptor mediated. In contrast, prolongation of the mean TFL found in the rat model of thioacetamide-induced acute hepatocellular necrosis was not reversed by (-)-naloxone, indicating that antinociception in this model is not opioid mediated. These findings provide support for the hypothesis that cholestasis is associated with increased opioidergic tone.
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PMID:Cholestasis in the male rat is associated with naloxone-reversible antinociception. 820 Dec 27

Cholestasis is associated with increased activity of the endogenous opioid system that results in analgesia. Endocannabinoid system can reduce pain sensitivity. Considering the interaction that has been shown between the endogenous opioid and endocannabinoid systems in nociception processing, we studied the effect of AM404, an endocannabinoid transport inhibitor, on modulation of nociception in cholestasis, a model of elevated endogenous opioid tone. Cholestasis was induced by ligation of the main bile duct using two ligatures and transection of the duct at the midpoint between them. A significant increase (P<0.01) in TF was observed in cholestatic rats compared to unoperated and sham rats. AM404 (10 mg/kg, i.p.) significantly increased TFL at 5, 30 min but not 60 min after injection in cholestatic animals compared to the vehicle treated cholestatic group (P<0.05, P<0.001, respectively). AM404 injection to unoperated and sham rats did not alter baseline TFL. The effect of AM404 in cholestatic rats was blocked by co-administration of a CB(1) receptor antagonist, AM251 (1 mg/kg, i.p.) but not by the CB2 receptor antagonist, SR144528 (1 mg/kg, i.p.). Naloxone injection blocked the antinociception induced by cholestasis in bile duct ligated group. Antinociception produced by injection of AM404 in cholestatics was also attenuated by co-administration of naloxone. These data show that AM404 potentiates antinociception induced by cholestasis and indicate that there are possible interactions between opioid and cannabinoid systems in this experimental model of elevated endogenous opioid tone. The inhibitory effects of AM404 in this model are mediated by cannabinoid CB(1) and not CB(2) receptors.
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PMID:The endocannabinoid transport inhibitor AM404 modulates nociception in cholestasis. 1961 63

Sucrose ingestion is reported to produce an initial (20-30min) analgesia and late (<5h) hyperalgesia. However, the influence of the characteristics of noxious stimuli and sweet substances on the pattern of transition from analgesia to hyperalgesia is not known. Therefore, we investigated the effect of sucrose (20%, sucrose fed group), saccharin (0.1%, saccharin fed group) and water ingestion (control group) on pain responses to various noxious stimuli for 5h. Latency of motor response of tail (TFL), paws to noxious thermal stimuli, threshold for elicitation of motor responses to electrical stimulation of tail nociceptive afferents in 5 sessions (0, 0.25, 1, 3 and 5h) and pain-related behavior to tonic noxious stimulus in 3 sessions at 1, 3 and 5h were recorded. In sucrose fed rats as compared to controls, the TFL sequentially increased (9.29+/-0.47s from 8.41+/-0.25; p<0.01), recovered to base-line and decreased (6.61+/-0.61sec; p<0.0001) in sessions II, III and V indicating analgesia, eualgesia and hyperalgesia, respectively. In saccharin fed rats the initial analgesia extended until session III followed by eualgesia and hyperalgesia in sessions IV and V. Pain related behaviour to tonic noxious stimulus also indicated an initial analgesia (0-5min), intermediate eualgesia and late hyperalgesia (3-5h) in sucrose fed rats, whereas only analgesia in saccharin fed rats. The results of our study suggest that sucrose ingestion for 5h leads to a bi-phasic response to both phasic and tonic noxious stimuli, albeit there are variations in their durations. Therefore, the temporal relationship of the nociceptive responses to palatable food is a function of the stimulus quality of both.
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PMID:Pattern of biphasic response to various noxious stimuli in rats ingesting sucrose ad libitum. 2058 Jun 42