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

We have examined the effects of extradural clonidine 150 micrograms or morphine 4 mg on postoperative pain, stress responses, cardiopulmonary function and motor and sensory block in a double-blind, randomized study in 20 patients undergoing hysterectomy with general anaesthesia. Observations were made for 6 h after each patient's first request for analgesia. Clonidine provided greater pain relief than morphine only for the first 2 h of observation (P less than 0.001). Plasma cortisol concentrations decreased to a greater extent (P less than 0.05) with morphine, while plasma glucose concentration increased by a similar extent in both groups. After clonidine, mean arterial pressure decreased from 100 (SEM 3) mm Hg to 70 (3) mm Hg (P less than 0.05), but there was no change after morphine. There were no significant changes in heart rate, pulmonary function (FEV1), motor function or sensory analgesia to touch, temperature and pinprick in both groups. Additional systemic opioids were required by five and six patients in the clonidine and morphine groups, respectively.
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PMID:Comparison of the effects of extradural clonidine with those of morphine on postoperative pain, stress responses, cardiopulmonary function and motor and sensory block. 251 58

Dose-response curves for clonidine-produced analgesia in rats were constructed using the tail-flick and formalin tests. Subsequently, the relative role of alpha 1 and alpha 2 receptors in clonidine analgesia in each of these tests was determined using systemic administration of vehicle controls, tolazoline, yohimbine and prazosin prior to injection of an ED50 dose of clonidine. Clonidine was found to be significantly more potent in the formalin test than in the tail-flick test. Furthermore, clonidine analgesia in the tail-flick test was completely antagonized by tolazoline and yohimbine, but not by prazosin, whereas clonidine was antagonized by tolazoline and prazosin, but not by yohimbine in the formalin test. The implications of these findings with regard to the contributions of different alpha-receptor subtypes to clonidine-produced analgesia in different pain tests are discussed.
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PMID:Different alpha-receptor subtypes are involved in clonidine-produced analgesia in different pain tests. 253 53

The possible involvement of endogenous opioid peptides in the cardiovascular responses observed following central alpha-adrenoceptor stimulation with clonidine, alpha-methyldopa (alpha-MD), and 6-hydroxydopamine (6-OHDA) was examined in conscious normotensive Wistar and spontaneously hypertensive (SHR) rats. Clonidine [2.5 micrograms intracisternally (i.c.)] produced rapid hypotension (-36 +/- 2 mm Hg) and bradycardia (-53 +/- 5 beats/min) in SHR that were similar to observations in animals given either naloxone (50 micrograms i.c. or 10 mg/kg i.p.) or appropriate saline control injections. Peripheral doses of naloxone (1-2 mg/kg) or saline did not further change arterial pressure or heart rate in either Wistar rats or SHR given alpha-MD (1.0 mg i.c.) 3 h earlier. In addition, central doses of naloxone (3 X 50 micrograms i.c.) given at hourly intervals did not affect the responses to alpha-MD. Central administration of 6-OHDA acutely releases noradrenaline which produces an initial fall in arterial blood pressure and heart rate. Intracisternal 6-OHDA (400 micrograms) produced similar time course and maximum circulatory effects in rats given naloxone (50 micrograms i.c. before and at each subsequent hour) as in saline-treated animals. Naloxone (1 mg/kg s.c.) significantly attenuated morphine-induced analgesia. These findings do not support a critical role of endogenous opioids in mediating the acute antihypertensive actions of clonidine and alpha-MD or in the cardiovascular responses produced by noradrenaline release following central 6-OHDA.
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PMID:Cardiovascular responses to central clonidine, alpha-methyldopa, and 6-hydroxydopamine in conscious normotensive and spontaneously hypertensive rats following naloxone. 258 Oct 87

Experimental data and anecdotal clinical observations have shown that clonidine, an alpha 2-agonist, has a marked analgesic effect. We investigated clonidine-induced analgesia in response to nociceptive stimuli. On 2 different days 7 normal volunteers received either placebo or clonidine (200 micrograms) orally according to a cross-over, double-blind, randomized, placebo-controlled design. Analgesia was assessed by measurement of the subjective (VAS) and objective (R III reflex) pain thresholds. A close correlation was observed between subjective and objective pain thresholds (r = 0.88, y = 0.2 + 1.2 x). Clonidine increased the objective threshold by 21% (+6.2 mA, SEM 2.4) and the subjective threshold by 10% (+2.4 mA, SEM 1.3). Drug effect was rapid (peak between 90 and 120 min) and overall analgesia lasted up to 4 hours. Side effects were a moderate fall in blood pressure, sedation and dryness of the mouth. A single oral dose of clonidine induces significant analgesia. These results suggest that clonidine is potentially a worthwhile drug for pain treatment which deserves further clinical investigation.
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PMID:[Analgesic effects of an oral dose of clonidine]. 261 77

The effects of intrathecal clonidine on spinal fentanyl analgesia were studied by the hot-plate test (52.0 degrees C) in rats. Clonidine (5 micrograms) and/or fentanyl (5 micrograms) were administered alone or combined in volume of 10 microliters through a chronically-implanted polyethylene catheter (PE-10) whose tip was near the lumbar enlargement of the spinal cord. Injections were done repeatedly every two or three days to determine the time course of thermal analgesia. Results were as follows; 1) Intrathecal clonidine (n = 5) produced no thermal analgesia. 2) Intrathecal fentanyl (n = 10) produced a profound thermal analgesia which was attenuated markedly by the repeated injections in six rats before the 9th injection. 3) Two out of six fentanyl tolerated rats responded with remarkable increases in thermal thresholds following the intrathecal clonidine with fentanyl. 4) Rats which were administered with both clonidine and fentanyl from the 1st injection (n = 9) responded with a extended prolongation of the escape latency, compared with the rats which received fentanyl only. In this group, the tolerance developed in only three animals by the 9th injection. In conclusion, combined intrathecal administration of clonidine with fentanyl potentiated the analgesic effect of fentanyl and then definitely suppressed the tolerance formation even if a small dose of clonidine which produces no analgesic effect was used. These results suggest that intrathecal or epidural administration of clonidine with narcotics might be useful in managing intractable pain.
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PMID:[Intrathecal clonidine--how does it work in spinal fentanyl analgesia in rats?]. 272 14

Epidural clonidine administration produces analgesia by a spinal action but may produce hemodynamic depression by activating other central or peripheral alpha 2-adrenoceptors. To determine clonidine's distribution and cardiorespiratory effects 300 micrograms clonidine was injected epidurally, intrathecally, and intravenously in six chronically prepared sheep, and cerebrospinal fluid (CSF) and arterial plasma clonidine were measured. Dural transfer of epidurally administered clonidine was rapid and extensive: time to maximal concentration (Tmax) in CSF was 32 +/- 8 min, bioavailability in CSF was 14 +/- 4% of the administered dose, and maximal CSF concentrations following epidural administration (820 +/- 30 ng/ml) were three orders of magnitude greater than those following iv injection (0.71 +/- 0.06 ng/ml). Systemic absorption of epidurally administered clonidine occurred rapidly: Tmax in plasma was 34 +/- 6 min and plasma concentrations were similar to those following iv injection at all time points beyond 20 min. Elimination half-lives from plasma were similar for all three routes of administration (81-95 min). Clonidine's effect on blood pressure differed with route of administration. Blood pressure increased and heart rate decreased following iv injection when plasma clonidine concentrations were high (greater than 2 ng/ml). Clonidine, following all routes of administration, numerically decreased blood pressure, but this decrease was significant only following epidural (mean arterial pressure = 97 +/- 6 mmHg before, 86 +/- 6 mmHg after; P less than 0.05) and intrathecal (93 +/- 9 mmHg before, 79 +/- 10 mmHg after; P less than 0.05) injection. Blood pressure decreased earlier following intrathecal than following epidural injection, corresponding with higher CSF clonidine concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pharmacokinetics and dynamics of intravenous, intrathecal, and epidural clonidine in sheep. 277 69

Epidurally administered clonidine has been reported to produce postoperative analgesia. To assess the efficacy, safety, and appropriate dose of epidural clonidine for postoperative analgesia, clonidine (range, 100-900 micrograms in 100-micrograms increments) was injected in 22 patients following abdominal surgery or total knee arthroplasty (TKA). Clonidine produced analgesia, as measured by change in verbal pain scores and supplemental iv morphine usage. The largest doses examined (700-900 micrograms) produced complete pain relief for 5.0 +/- 0.8 h (mean +/- SEM; range 2-11 h), without other sensory or motor blockade. Clonidine also produced dose dependent decreases in blood pressure, being less following small (100-300 micrograms) and large (700-900 micrograms) doses than following intermediate (400-600 micrograms) doses. Six patients required iv ephedrine for treatment of blood pressure decrease of greater than 30%. Clonidine decreased heart rate 10-30% and produced transient sedation. Oxyhemoglobin saturation, serum glucose, and arterial blood gas tensions were not altered by clonidine, whereas there was a small (28%) dose-independent decrease in serum cortisol following clonidine injection. Clonidine was absorbed in a dose-dependent manner into the systemic circulation, with plasma concentrations 0.1-3.3 ng/ml 1 h following injection. These results suggest that hemodynamic depression and short-lasting analgesia may limit the usefulness of bolus epidural clonidine analgesia in the postoperative setting.
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PMID:Epidural clonidine analgesia following surgery: phase I. 281 56

Intrathecally administered clonidine has been reported to produce analgesia in cancer patients tolerant to intrathecal opiates. To assess the efficacy, safety, and appropriate dose of epidurally administered clonidine for the treatment of cancer pain, clonidine (range, 100-900 micrograms in 100-micrograms increments) was injected in nine patients with severe, intractable cancer pain. Clonidine produced analgesia, as measured by change in verbal pain scores, lasting more than 6 h. Clonidine also decreased blood pressure, although this effect was well tolerated and no patient met criteria for receiving iv ephedrine (greater than 30% decrease in mean arterial pressure not responsive to 500 ml iv crystalloid infusion). Clonidine decreased heart rate 10-30% and produced transient sedation. Serum glucose and cortisol and oxyhemoglobin saturation were not altered by clonidine. Clonidine was absorbed in a dose-dependent manner into the systemic circulation, although absorption and elimination kinetics were highly variable. Following study seven patients received epidural clonidine/morphine infusions at home for periods of up to 5 months with sustained analgesia. These results suggest that epidurally administered clonidine may offer effective analgesia in patients with severe, intractable cancer pain.
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PMID:Epidural clonidine analgesia for intractable cancer pain: phase I. 281 57

Clonidine has been reported to produce analgesia in humans in different painful conditions. The aim of the present study was to investigate if epidural clonidine produced a clinically important analgesia to severe postoperative pain. Using a controlled, randomized double-blind design, one group of patients received a single dose of epidural clonidine 3 micrograms/kg (n = 10) and a control group epidural 0.9% saline (n = 10), when reporting postoperative pain after thoracotomy performed under standardized anaesthesia. To quantify the effects of the given epidural drugs, the need for supplementary, intravenous pethidine analgesia was recorded. The patients had access to the supplementary analgesic by means of a patient-controlled analgesic-delivery device. The two groups were similar regarding anthropometric and clinical data. Epidural clonidine 3 micrograms/kg did not affect the need for supplementary intravenous pethidine analgesia, as compared to the control group at any time during the first 12 h postoperatively. The side-effects of epidural clonidine were tolerable, and no treatment for arterial hypotension was required. No early or delayed respiratory depression occurred. In conclusion, clonidine 3 micrograms/kg epidurally seems to lack clinically important analgesic effects on severe postoperative pain, at least following thoracotomy.
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PMID:Epidural clonidine for treatment of postoperative pain after thoracotomy. A double-blind placebo-controlled study. 306 48

Clonidine analgesia was tested on the hyperalgesia induced by intraplantar injection of prostaglandin E2 or carrageenin. The antinociceptive effect of clonidine was dose-dependent and was abolished by local administration of the selective alpha 2-adrenoceptor blocker, yohimbine or of the opioid antagonists naloxone or quaternary nalorphine. St-91, a clonidine analog which does not cross the blood-brain barrier also promoted significant antinociception. Repeated administration of drugs possessing a central mechanism of analgesic action leads to the development of tolerance in this test. Significant analgesic tolerance was observed following repeated (5 days) morphine (8 mg/kg) or high doses of clonidine (0.5 mg/kg). In contrast, no tolerance was detected to the analgesic effect of low doses of clonidine (0.15 mg/kg) or of St-91 (0.5 mg/kg). These results suggest that, in addition to its central analgesic action, clonidine can induce peripheral antinociception by an alpha 2-adrenoceptor-mediated local release of enkephalin-like substances.
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PMID:Peripheral analgesic action of clonidine: mediation by release of endogenous enkephalin-like substances. 316 52


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