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)

1. Male Sprague-Dawley rats were fitted with intrathecal (i.t.) and intracerebroventricular (i.c.v.) catheters. Fentanyl was injected either i.t. or i.c.v., and the antinociceptive efficacy of fentanyl was evaluated using the tail-flick analgesiometric assay. 2. Fentanyl dose-dependently elevated tail-flick latency (TFL) following i.c.v. or i.t. administration. The antinociceptive effects of fentanyl were reversed by naltrexone. 3. Experiments were also designed to evaluate the effects of serotonin and alpha-adrenoceptor antagonists on i.t. or i.c.v. fentanyl-induced elevations in TFL. 4. Phentolamine administered i.t. reversed both the spinal and supraspinal antinociceptive effects of fentanyl, whereas i.t. methysergide did not significantly alter the i.t. or i.c.v. effects of the mu agonist. 5. These data suggest that fentanyl-induced antinociception does not rely on local serotonergic neuronal activation. Due to the highly lipophilic nature of fentanyl, it is possible that the noradrenergic component contributing to spinal fentanyl-induced analgesia is supraspinally-mediated.
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PMID:The noradrenergic component contributing to spinal fentanyl-induced antinociception is supraspinally mediated. 133 47

Participation of opiate, serotonergic and noradrenergic components in the antinociceptive action of intrathecally administered morphine was evaluated by measuring the ability of subcutaneously administered doses of naloxone, methysergide and phentolamine to alter analgesia. Morphine produced a dose-dependent elevation of the tail-flick latency, due exclusively to local spinal actions. For example, 10 nmol of the drug, when administered intrathecally in rats with bilateral lesions of the dorsolateral funiculus, produced an increase in the tail-flick latency, that was similar to that observed in intact animals. Furthermore, morphine was ineffective when administered intracerebroventricularly into the fourth ventricle of intact rats. The spinal antinociceptive action of the opiate was antagonized by naloxone (ID50 = 0.035 mg/kg, s.c.) but was also significantly attenuated by methysergide (ID50 = 4.28 mg/kg, s.c.). Phentolamine was ineffective. Doses of methysergide that were most effective in reversing the spinal action of morphine also produced hyperalgesia when administered alone. On the other hand, when the dorsolateral funiculus was lesioned, the hyperalgesia was no longer observed, yet the antagonist remained effective against morphine. These data suggested that the doses of methysergide needed to antagonize the action of morphine were in the same range as those needed to block the synaptic actions of serotonin (5-HT) released from the tonically-acting, descending pain inhibitory nerves. The results demonstrate that local opiate, as well as serotonergic, mechanisms mediate the antinociceptive action of morphine in the spinal cord. The recruitment of a serotonergic component may be related to an action of opiates within the spinal cord, to cause the release of serotonin from the terminal fields of the spinipetal serotonergic nerves.
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PMID:A local serotonergic component involved in the spinal antinociceptive action of morphine. 255 80

With electric stimulation of the splanchnic nerve or the skin of the tip of rabbit's ear to measure visceral or somatic pain threshold, we studied the effects of noradrenaline microinjection into the septal nucleus on visceral pain and somatic pain and the relationship between the intraseptal noradrenaline and the intra-PAG opiate peptidergic system. There was no effect on visceral pain threshold after injections of alpha-agonist clonidine (10 micrograms/2 microliters) or alpha-antagonist phentolamine (10 micrograms/2 microliters). In a group injected with beta-agonist isoprenaline (1 micrograms/2 microliters), visceral pain threshold was raised remarkably, while beta-antagonist propranolol (10 micrograms/2 microliters) injected into bilateral septal nuclei decreased visceral pain threshold. Phentolamine (10 micrograms/2 microliters) or propranolol (10 micrograms/2 microliters) injected into septal nucleus induced an elevation of somatic pain threshold. The results indicate that the beta-receptor in spetal nucleus plays an important role in the modulation of visceral pain. Both alpha-and beta- adrenergic receptors have effects on the modulation of somatic pain. Intra-PAG microinjection of naloxone (1 micrograms/1 microliters) attenuated visceral analgesia produced by injection of isoprenaline (1 micrograms/2 microliters) into septal nucleus. Microinjection of anti-leu-enkephalin antiserum (1:20,000) into PAG also attenuated the analgesia. When microinjection of isoprenaline into septal nucleus produced analgesia, the release of leu-enkephalin immunoreactive-like-substance in PAG was significantly increased. The results suggest that the analgesic effect of intra-septal noradrenaline on visceral pain is somehow related with the endogenous opiate peptidergic system in PAG, and the leu-enkephalin in PAG plays an important role in this process.
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PMID:[Effect of intraseptal noradrenaline on somatic and visceral pain threshold of rabbits]. 276 39

Spinal intrathecal injections of the nonsteroidal antiinflammatory analgesics (NSAIAs) indomethacin and acetylsalicylic acid, which inhibit prostaglandin synthesis, cause dose-dependent hypoalgesia in the rat. Intrathecal injections of prostaglandin-E2 (PGE2) produce dose-dependent hyperalgesia. To determine whether this action of prostaglandins on the central nervous system is mediated through pain-generating or analgesia pathways, we studied the effect of intrathecal PGE2 on endogenous opioid-induced analgesia. Intrathecal PGE2 antagonized the analgesia produced by both brain stimulation and intracerebroventricular morphine. In contrast, the NSAIAs synergized with brain stimulation and morphine-induced analgesia. The alpha-adrenergic antagonist phentolamine and the catecholaminergic selective neurotoxin 6-hydroxydopamine, used to block tonic catecholamine activity in endogenous opioid-mediated analgesia systems, prevented the hyperalgesia induced by intrathecal PGE2. Phentolamine did not, however, block the hyperalgesia caused by intradermal PGE2. These findings suggest that prostaglandins can block endogenous opioid-mediated analgesia systems by inhibiting the bulbospinal noradrenergic component of this analgesia pathway.
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PMID:Prostaglandins inhibit endogenous pain control mechanisms by blocking transmission at spinal noradrenergic synapses. 283 84

The effects of the alpha-adrenoceptor antagonists prazosin, phentolamine and yohimbine upon 5-methoxy-N,N-dimethyltryptamine (5-MeODMT)-induced analgesia were tested in the hot-plate, tail-flick and shock-titration tests of nociception with rats. Intrathecally injected yohimbine and phentolamine blocked or attenuated the analgesia produced by systemic administration of 5-MeODMT in all three nociceptive tests. Intrathecally administered prazosin attenuated the analgesic effects of 5-MeODMT in the hot-plate and tail-flick tests, but not in the shock titration test. Intrathecal yohimbine showed a dose-related lowering of pain thresholds in saline and 5-MeODMT-treated animals. Phentolamine and prazosin produced normal dose-related curves in the hot-plate test and biphasic effects in the shock titration and tail-flick tests. These results demonstrate a functional interaction between alpha 2-adrenoceptors and 5-HT agonist-induced analgesia at a spinal level in rats.
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PMID:5-Methoxy-N,N-dimethyltryptamine-induced analgesia is blocked by alpha-adrenoceptor antagonists in rats. 287 97

The involvement of a catecholaminergic mechanism in the production of morphine analgesia and the development of tolerance to the effect has been suggested. Here, using various adrenergic blockers, the role of adrenergic function in the mechanism was examined. Phentolamine (alpha 1 + alpha 2-blocker, 10, 1 and 0.5 mg/kg), prazosin (alpha 1-blocker, 0.1 and 0.02 mg/kg), propranolol (beta 1 + beta 2-blocker, 10, 1 and 0.5 mg/kg), metoprolol (beta 1-blocker, 10 and 1 mg/kg) did not affect morphine analgesia, but dose-dependently suppressed the development of tolerance to morphine. Yohimbine (alpha 2-blocker, 5 and 1 mg/kg) dose-dependently antagonized morphine analgesia in naive animals and delayed the development of tolerance to morphine. Pindolol (beta 1 + beta 2-blocker but is devoid of membrane stabilizing activity) suppressed the development of tolerance to morphine analgesia; however, d-propranolol, which possesses membrane stabilizing activity but lacks beta-blocking activity, could not prevent the development of tolerance. Thus, the suppressive effect of propranolol on the development of tolerance is not due to membrane stabilizing properties. Not only the non-selective adrenergic blockers, phentolamine and propranolol, but also the selective blockers of each receptor subtype, prazosin and metoprolol, suppressed the development of tolerance. This fact may suggest the importance of the equilibrated state of adrenergic functions in the mechanism for the development of tolerance to morphine.
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PMID:Important role of adrenergic function in the development of analgesic tolerance to morphine in mice. 288 Oct 17

Continuous cold water swim produces analgesia that is partially mediated by a noradrenergic mechanism, but is independent of both serotonergic and opioid systems. On the other hand, intermittent cold water swim elicits analgesia which is partly mediated by an opioid mechanism; the contribution of the monoamines to the production of this analgesia is not known. Therefore, the present study was done to determine whether intermittent cold water swim is also mediated by noradrenergic and/or serotonergic substrates. Prior to either continuous (3.5 min) or intermittent (10 sec in, 10 sec out for 6 min) cold water (4 degrees C) swim, male Sprague-Dawley rats (225-250 g) were administered either the noradrenergic receptor blocker phentolamine (30 micrograms), the serotonergic blocker methysergide (30 micrograms) or artificial cerebrospinal fluid to the fifth lumbar vertebral spinal level via chronic intrathecal catheters. Phentolamine significantly attenuated the analgesia resulting from both continuous and intermittent cold water swim. Methysergide attenuated intermittent cold water swim analgesia, but was without effect on continuous cold water swim analgesia. Phentolamine, but not methysergide, also attenuated continuous footshock- (2.5 mA for 3 min) induced analgesia. The similarity between the effects of phentolamine and methysergide on continuous footshock and continuous cold water swim analgesia suggests that the effects of these drugs on cold water swim analgesia are not attributable to changes in thermoregulation. These results suggest that a spinal noradrenergic mechanism is involved in the mediation of both forms of cold water swim analgesia, whereas a spinal serotonergic mechanism is involved in only intermittent cold water swim analgesia.
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PMID:Analgesia induced by continuous versus intermittent cold water swim in the rat: differential effects of intrathecal administration of phentolamine and methysergide. 325 57

The analgesic effect of protopine (Pro), an alkaloid isolated from Papaveraceae, was confirmed by tail-pinch and hot-plate tests when given sc 10-40 mg.kg-1, and 20-40 mg.kg-1 inhibited the spontaneous movements of mice. Pro 40 mg.kg-1 increased the sleeping rate, prolonged the sleeping duration, and shortened the sleeping latency in mice hypnotized by ip pentobarbital sodium 30 mg.kg-1. Pro 10-40 mg.kg-1 did not affect the inflammatory reaction induced by xylene and egg white. An icv injection of Pro 20-200 micrograms/mouse showed a remarkable analgesic effect in mice. The icv pretreatment of naloxone 2 micrograms blocked the analgesic effect completely. CaCl2 40 micrograms/mouse (ICV) or methotrexate 10 mg.kg-1 (ip), an agonist of Ca2+ channel, showed a complete blockade of the analgesia, while nifedipine 100 mg.kg-1(po), a blocker of Ca2+ channel, enhanced the analgesic effect. The ip pretreatment of reserpine 4 mg.kg-1 reduced the Pro analgesia. Phentolamine 10 mg.kg-1(ip), an alpha-adrenergic blocker, tended to weaken the analgesia, but propranolol 10 mg.kg-1(ip), a beta-blocker, did not affect it. These results suggest that Pro displays its analgesic effect mainly through the opioid and calcium systems and partly through the adrenergic mechanism.
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PMID:Opioid, calcium, and adrenergic receptor involvement in protopine analgesia. 801 45

Phentolamine, a nonspecific alpha 1- and alpha 2-adrenergic antagonist, relieves pain in patients with reflex sympathetic dystrophy. We sought to determine whether phentolamine, prazosin (alpha 1 antagonist), or SKF86466 (alpha 2 antagonist) relieve thermal hyperalgesia in rats with neuropathic pain. Four days after producing a chronic constriction injury (CCI), thermal hyperalgesia was tested by measuring paw withdrawal latency (PWL). After injection of phentolamine, prazosin, or SKF86466 each at doses of 1, 2, or 5 mg/kg, PWL tests were measured at 5 min and repeated at 15-min intervals for 1 h. Phentolamine, prazosin, and SKF86466 1, 2, and 5 mg/kg provided statistically significant analgesia in rats with CCI for at least 65 min. PWL did not return to baseline levels after 1 or 2 mg/kg of prazosin or SKF86466 but did so after 35 min after phentolamine 2 mg/kg. After 5 mg/kg, PWL returned to preoperative values between 5 and 50 min for phentolamine, at 35 and 65 min for prazosin, and at 50 min for SKF86466. We conclude that both alpha1 and alpha2 peripheral receptors of the sympathetic nervous system are involved in the thermal hyperalgesia caused by CCI and that thermal hyperalgesia can be reversed by both alpha1 and alpha2 antagonists in a dose-dependent manner.
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PMID:alpha-1 and alpha-2 Adrenergic antagonists relieve thermal hyperalgesia in experimental mononeuropathy from chronic constriction injury. 1137 46