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Query: UMLS:C0344307 (analgesia)
 28,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Clonidine, when administered for prolonged period showed no tolerance to its analgesic activity. Prior exposure to clonidine attenuated the tolerance development to morphine-induced analgesia and the supersensitivity to acetylcholine (ACh) in ileum during chronic morphine treatment. Further, acute administration of lower doses of clonidine (upto 1 mg) produced supersensitivity in ileum to Ach while the higher dose (10 mg) induced subsensitivity. In vas deferens, clonidine in all the concentrations tested induced dose and time dependent supersensitivity to norepinephrine (NE) similar to that produced by morphine. Chronic clonidine treatment failed to alter the ACh responses in ileum while it produced supersensitivity to NE in vas deferens. The results suggest that clonidine and morphine possess comparable properties and the antagonism of chronic morphine tolerance by clonidine may be the therapeutic basis for its clinical application in the treatment of opiate addicts.
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PMID:Effect of clonidine on the chronic morphine tolerance and on the sensitivity of the smooth muscles in mice. 688 70

In the rat the effects of clonidine and xylazine were compared on a measure of analgesia (tail-withdrawal from hot water) and on operant responding maintained by a fixed-ratio 20-response schedule of food presentation. Clonidine (2--8 mg/kg) produced dose-dependent increase in tail-withdrawal latency and was approximately twice as potent as xylazine (8--16 mg/kg) in this test. This analgesic effect of 8 mg/kg of clonidine was antagonized by phenoxybenzamine (10 mg/kg), and high doses of yohimbine (5--10 mg/kg), whereas the effect of 2 mg/kg of clonidine was potentiated by a nonanalgesic dose of nisoxetine (10 mg/kg). Clonidine (0.0063--0.2 mg/kg) and xylazine (0.25--8 mg/kg) produced a dose-dependent suppression of fixed-ratio responding. The potency of clonidine in this task was approximately 40 times greater than that of xylazine. The suppression of responding produced by both drugs was antagonized by low doses of yohimbine (0.5--2 kg/mg), which was maximally effective at a dose of 1 mg/kg. The data suggest that when using this type of assay for analgesia, the antinociceptive effects of clonidine which are measured are a result of stimulation of alpha-adrenergic receptors or noradrenergic neurons or by adrenergic receptors which inhibit noradrenergic neurons.
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PMID:Clonidine analgesia and suppression of operant responding: dissociation of mechanism. 697 Jun 65

Clonidine, 0.25 and 0.5 mg/kg, depressed significantly the running fit induced by 10 or 20 mg/kg of morphine in C57BL/6 mice, but did not affect morphine analgesia measured by the "hot plate" test. The results confirm the hypothesis that different mechanisms are involved in the two types of response to morphine, and the running fit response is mediated via a noradrenergic mechanism of action.
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PMID:Inhibition by clonidine of morphine-induced running fit but not analgesia in C57BL/6 mice. 719 61

Although the vast majority of patients with cancer pain receive effective analgesia from standard therapy, a few patients, particularly those with neuropathic pain, continue to experience severe pain despite large doses of systemic or intraspinal opioids. Animal studies suggest intraspinal alpha 2-adrenergic agonists may be effective in such cases. Eighty-five patients with severe cancer pain despite large doses of opioids or with therapy-limiting side effects from opioids were randomized to receive, in a double-blind manner, 30 micrograms/h epidural clonidine or placebo for 14 days, together with rescue epidural morphine. Pain was assessed by visual analog score (VAS), McGill Pain Questionnaire, and daily epidural morphine use. Success was defined as a decrease in either morphine use of VAS pain, with the alternative variable either decreasing or remaining constant. Blood pressure, heart rate, and degree of nausea and sedation were monitored. Successful analgesia was more common with epidural clonidine (45%) than with placebo (21%). This was particularly prominent in those with neuropathic pain (56% vs. 5%). Pain scores were lower at the end of the treatment period in patients with neuropathic pain treated with clonidine rather than placebo, whereas morphine use was unaffected. Clonidine, but not placebo, decreased blood pressure and heart rate. Hypotension was considered a serious complication in 2 patients receiving clonidine and in 1 patient receiving placebo. This study confirms the findings from previous animal studies which showed the effective, potent analgesic properties of intraspinal alpha 2-adrenergic agonists and suggests that epidural clonidine may provide effective relief for intractable cancer pain, particular of the neuropathic type.
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PMID:Epidural clonidine analgesia for intractable cancer pain. The Epidural Clonidine Study Group. 747 82

Both epidural and intravenous clonidine are used to provide postoperative analgesia, but in predetermined doses. This double-blind randomized study was designed to 1) determine the clonidine dose inducing pain relief after major orthopedic surgery, when controlled by patient, either intravenously or epidurally; and 2) assess whether these two administration routes are clinically equivalent. At the first complaint of pain after scoliosis correction, patients received an initial dose of 8 micrograms/kg clonidine during 30 min either intravenously (n = 12) or epidurally (n = 12). Then, clonidine was given using a patient-controlled analgesia pump via the corresponding administration route. In both cases, the bolus dose was set at 30 micrograms and the lockout interval at 15 min. Pain (0-100 scale), clonidine requirements, sedation (0-4 scale), and hemodynamics (by fiberoptic pulmonary artery catheter) were measured before and 15, 30, 120, 240, 360, 480, and 600 min after the loading dose was started. Plasma clonidine concentrations and arterial blood gases were determined at the 15th, 30th, 240th, and 480th min. Self-administered and total clonidine doses were larger in the intravenous group than in the epidural group (at 600 min: 372 +/- 110 vs 235 +/- 144 micrograms, and including the initial dose, 814 +/- 114 vs 652 +/- 187 micrograms; mean +/- SD). Clonidine administration resulted in pain relief and sedation in both groups but, for comparable pain relief, sedation scores were lower in the epidural group. No intergroup differences in hemodynamic data were observed, although the decrease in blood pressure occurred earlier in the intravenous group. Plasma clonidine concentrations were higher in the intravenous group than in the epidural group (2.5 +/- 0.6 vs 1.5 +/- 0.5 ng/mL after the initial dose and 2.1 +/- 0.5 vs 1.5 +/- 0.4 ng/mL during self-administration; mean +/- SD). We conclude that analgesia can be achieved postoperatively by both epidural and intravenous clonidine administration. The epidural route is associated with significant reductions in self-administered clonidine dose, and thus in the plasma clonidine concentration, and the level of sedation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparison of intravenous and epidural clonidine for postoperative patient-controlled analgesia. 757 98

Although the epidural administration of clonidine and fentanyl provides pain relief after surgery, the interaction between the two drugs has not been examined formally. This study used an isobolographic method to determine whether epidurally administered fentanyl and clonidine interact in an additive or synergistic manner. Ninety women with moderate to severe pain after elective cesarean section under epidural anesthesia were studied. Using a randomized, double-blind protocol, we assigned each patient to receive a single epidural injection of one of three doses of fentanyl, clonidine, or a fixed ratio combination. Pain relief, blood pressure (BP), heart rate (HR), and sedation were measured 15 min after injection. Each drug alone and in combination produced analgesia, as measured by pain relief scores, and reduced need for intravenous morphine. Although the effective dose producing analgesia in 50% of patients (ED50) for the mixture was only 52% of that predicted by an additive interaction, this did not differ significantly from additivity, likely due to large variability. Clonidine, alone or in combination with fentanyl, produced a minor reduction in BP, but did not affect HR or cause more sedation than fentanyl. Unlike studies in rodents, this clinical study did not demonstrate synergy between fentanyl and clonidine. This could reflect a true species difference or differences in methodologies used. Nonetheless, a reduced dose of fentanyl and clonidine can be combined for excellent analgesia.
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PMID:An isobolographic study of epidural clonidine and fentanyl after cesarean section. 763 65

Clonidine in spinal and epidural blocks prolongs anesthesia, but can cause hypotension and bradycardia. The aim of our study was to compare hemodynamic and analgesic effects of spinal versus epidural clonidine alone and after repetitive dosing. In a prospective, randomized, double-blind study, we evaluated 40 patients scheduled for lower extremity orthopedic surgery under continuous spinal or epidural anesthesia with bupivacaine 0.5% (initial dose 5 mg and 50 mg, respectively). In either spinal or epidural technique one-half of patients received clonidine (150 micrograms) in addition to bupivacaine. Repeat doses of the same anesthetic mixture were allowed in cases of subsequent pain. Mean arterial pressure (MAP) and heart rate were recorded for 6 h after each injection. Duration of clinically useful anesthesia was defined as the time from drug administration to first sensation of pain. Intrathecal, but not epidural, clonidine decreased MAP significantly compared with bupivacaine alone. MAP after intrathecal clonidine with bupivacaine was lower than epidural clonidine with bupivacaine 5 and 6 h after injection. Repetitive administration caused no further decrease in MAP. Onset time required to surgical anesthesia (sensory block of T11) did not differ among the four groups. Duration of spinal and epidural anesthesia was increased more than two fold by clonidine. In summary, the addition of clonidine prolongs analgesia by either route. These results may be explained by clonidine's sites of action in hemodynamic control and the density of bupivacaine-induced block.
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PMID:Hemodynamic and analgesic effects of clonidine added repetitively to continuous epidural and spinal blocks. 781 20

Clonidine, an alpha-2-adrenergic agonist, may have a clinically relevant analgesic action but also a hypotensive action, when administered spinally. In this study, therefore, the analgesic and circulatory effects of intrathecal clonidine were studied in patients undergoing knee arthroscopy under spinal anaesthesia. Forty ASA I-II patients were randomly divided to two groups. One group received clonidine 3 micrograms.kg-1 mixed with 15 mg 0.5% bupivacaine and the other group an identical saline volume mixed with bupivacaine as above, in a double-blind fashion. Sensory analgesia, blood pressure, heart rate and sedation were followed during and after the operation. Oxycodone 0.14 mg.kg-1 i.m. or ketoprofen 100 mg p.o. was administered when needed. The duration of sensory analgesia (until regression of the block to L2) was longer in the clonidine group (mean 217 min) than in the control group (mean 160 min) (P < 0.05). Duration of motor blockade was also longer in the clonidine group (mean 215 min) compared to the control group (161 min) (P < 0.05). Mean arterial pressure and heart rate were significantly lower in the clonidine group compared to the control group. The clonidine patients needed fewer supplemental doses of oxycodone (8 doses) than those in the control group (16 doses) (P < 0.05). More patients in the clonidine group were sedated 3-6 h after the injection (P < 0.05). Addition of clonidine prolonged the bupivacaine spinal block. However, marked haemodynamic changes and sedation may limit the usefulness of intrathecal clonidine.
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PMID:Effects of intrathecal clonidine on duration of bupivacaine spinal anaesthesia, haemodynamics, and postoperative analgesia in patients undergoing knee arthroscopy. 783 85

Epidural opioids provide a potent analgesia not devoided of side effects. In addition, epidural administration of lipid soluble opioids has no clear advantage over the IV route. Combination of epidural opioids with other analgesics may strengthen analgesia and may decrease the incidence of side effects because of a reduction in the amount of opioid administered. Improvement in analgesia quality is documented when local anaesthetics are associated to opioids. Low concentrations of local anaesthetics may potentiate the effect of opioids on ions membrane channels at the level of the dorsal horn of the spinal cord. Alpha adrenergic agonists provide an alternative to local anaesthetics, allowing to improve pain control achieved with opioids. Epinephrine decreases plasma absorption of opioids and is especially useful to prolong the effect of short acting lipid soluble opioids. Alpha adrenergic agonists atc on alpha-2-adrenergic receptors of the spinal cord dorsal horn to depress pain nociceptive transmission. This effect potentiates the one of opioids at this level. Clonidine, which is a selective alpha-2-adrenergic agonist has been demonstrated to improve and to prolong analgesia produced by opioids in postoperative patients. Clonidine administration induces side effects, like sedation, bradycardia and hypotension, but allows to highly reduce the opioid dose. None of the combined techniques of analgesia implies that monitoring of the side effects of opioids has to be reduced.
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PMID:[Is there an advantage to using opioid combinations by the peridural route?]. 790 34

Mechanisms of the analgesic actions of alpha 2-adrenergic agonists are likely related to various modulating systems of nociceptive neurotransmission, especially those dependent on opiate receptors. Analgesic action of alpha 2-adrenergic agonists implies alpha 2-adrenergic receptors, strategically located on the dorsal horn neurones of the spinal cord to inhibit the release of substance P in response to peripheral stimuli. However, these receptors are included in the control that supraspinal sites exert via the descending medullospinal noradrenergic pathway. Because of its high lipophilic structure, alpha 2-adrenergic agonist can easily penetrate into the central nervous system, reproducing the effects of activation of medullospinal noradrenergic pathway. Alpha 2-adrenergic agonists have been found to be efficient in human pain treatment after systemic, spinal or troncular administration, but there were few randomized clinical studies comparing analgesia potency and adverse effects of either systemic or regional administrations. Clonidine added to local anaesthetic agents increases the analgesic effects in a greater extent than systemic administration of similar dose, probably because this effect depends on the local clonidine concentration. Extradural administration of clonidine is also more efficient than systemic administration, at least when high doses are injected. This superiority is questionable when low-dose clonidine is used. Adverse effects are quite similar in both systemic and spinal routes. Invasiveness of extradural route may be considered in regard to the gain which may be expected in analgesia efficiency.
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PMID:[Which way for the administration of alpha 2-adrenergic agents to obtain the best analgesia?]. 791 62


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