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Query: UMLS:C0030193 (pain)
261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In a prospective randomized study in children, we compared caudal bupivacaine-clonidine with bupivacaine-morphine to evaluate whether clonidine can be used as an alternative to morphine in caudal anaesthesia. Caudal anaesthesia was administered in 36 children undergoing orchidopexy, hernia repair or circumcision, using 1.5 mL kg-1 bupivacaine 0.18% with either 1 microgram kg-1 clonidine (group 1) or 30 micrograms kg-1 morphine (group 2). Haemodynamic and respiratory parameters, anaesthetic requirements, recovery time and pain score were monitored for 24 h. Eleven children in group 1 and nine children in group 2 did not need any supplementary systemic analgesics throughout the 24-h observation period. Mean (+/- SD) duration of analgesia in the remaining patients was 6.3 h (+/- 3.3 h) in group 1 and 7.1 h (+/- 3.4 h) in group 2 (P = 0.43). Recovery time after anaesthesia was significantly longer in group 1 (16.6 +/- 8.8 min) than in group 2 (11.5 +/- 4.7 min) (P < 0.05). We conclude that analgesia provided by 1 microgram kg-1 clonidine added to caudal bupivacaine is comparable with that provided by 30 micrograms kg-1 caudal morphine with bupivacaine. Clonidine at this low dose did not cause respiratory depression.
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PMID:Comparison of clonidine 1 microgram kg-1 with morphine 30 micrograms kg-1 for post-operative caudal analgesia in children. 1008

Disorders of pain sensation including spontaneous pain, allodynia and hyperalgesia are commonly seen in neuropathic diabetic patients. A wealth of evidence indicates that spinal monoamine systems are implicated in pain modulation but whether abnormalities in these systems underlay such disorders is unclear. The present study was therefore initiated to investigate spinal noradrenergic dynamics during diabetes. Spinal release of norepinephrine (NE) represented by 3-methoxy-4-hydroxyphenylglycol (MHPG)/NE ratio was markedly suppressed in 30-day streptozotocin (STZ)-treated diabetic male and female rats. The density of [3H] p-aminoclonidine binding sites and the level of expression of mRNA encoding for alpha2A-adrenoceptor subtype were also reduced as a function of diabetes. In contrast, an increase in the density of [3H] prazosin binding to spinal synaptosomal membranes was evident in these animals. Clonidine-induced elevation in nociceptive threshold was attenuated in diabetics. Control animals subjected to chronic treatment with a supraphysiological dose of glucocorticoid (GC) exhibited a neurochemical pattern which is similar in many respects to that produced by the diabetic state. Both insulin and the GC receptor blocker, RU 486, restored most of the neurochemical and behavioural abnormalities of diabetes. Overall, the present study supports the concept that a diabetes-related deficit in spinal noradrenergic dynamics may be a reflection of an overactivity of the hypothalamic-pituitary-adrenal axis.
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PMID:Spinal cord noradrenergic dynamics in diabetic and hypercortisolaemic states. 1035 May 53

alpha2-Adrenergic receptor (AR)-selective compounds produce antihypertensive and antinociceptive effects. Moxonidine alleviates hypertension in multiple species, including humans. This study demonstrates that intrathecally administered moxonidine produces antinociception in mice. Antinociception was detected via the (52.5 degrees C) tail-flick and Substance P (SP) nociceptive tests. Moxonidine was intrathecally administered to ICR, mixed C57BL/6 x 129/Sv [wild type (WT)], or C57BL/6 x 129/Sv mice with dysfunctional alpha2aARs (D79N-alpha2a). The alpha2AR-selective antagonist SK&F 86466 and the mixed I1/alpha2AR-selective antagonist efaroxan were tested for inhibition of moxonidine-induced antinociception. Moxonidine prolonged tail-flick latencies in ICR (ED50 = 0.5 nmol; 0. 3-0.7), WT (0.17 nmol; 0.09-0.32), and D79N-alpha2a (0.32 nmol; 0. 074-1.6) mice. Moxonidine inhibited SP-elicited behavior in ICR (0. 04 nmol; 0.03-0.07), WT (0.4 nmol; 0.3-0.5), and D79N-alpha2a (1.1 nmol; 0.7-1.7) mice. Clonidine produced antinociception in WT but not D79N-alpha2a mice. SK&F 86466 and efaroxan both antagonized moxonidine-induced inhibition of SP-elicited behavior in all mouse lines. SK&F 86466 antagonism of moxonidine-induced antinociception implicates the participation of alpha2ARs. The comparable moxonidine potency between D79N-alpha2a and WT mice suggests that receptors other than alpha2a mediate moxonidine-induced antinociception. Conversely, absence of clonidine efficacy in D79N-alpha2a mice implies that alpha2aAR activation enables clonidine-induced antinociception. When clinically administered, moxonidine induces fewer side effects relative to clonidine; moxonidine-induced antinociception appears to involve a different alpha2AR subtype than clonidine-induced antinociception. Therefore, moxonidine may prove to be an effective treatment for pain with an improved side effect profile.
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PMID:Moxonidine, a selective alpha2-adrenergic and imidazoline receptor agonist, produces spinal antinociception in mice. 1038 6

Clonidine is approved in the US for epidural administration in the treatment of intractable neuropathic cancer pain, but is also administered intrathecally for this indication and both epidurally and intrathecally in the treatment of acute, postoperative pain. The purpose of the current study was to estimate the relative potency of clonidine by epidural and intrathecal routes in the treatment of capsaicin-induced hyperalgesia and allodynia as a model of central hypersensitivity and of noxious heat as a model of acute pain. Twenty-four healthy volunteers were randomized to receive either intrathecal clonidine (75, 150, or 300 micrograms) or epidural clonidine (150, 300, or 600 micrograms) and rated pain from a Peltier-controlled thermode at a lumbar, thoracic, and cervical dermatomal site before and after drug administration. In addition, they rated pain from intradermal capsaicin injections at a lumbar dermatome before and 60 min after clonidine injection and described areas of hyperalgesia and allodynia to mechanical stimuli. Clonidine's effect differed with route of administration and modality of sensory testing. For acute thermal pain, intrathecal clonidine produced a dose-dependent analgesia with a lumbar>thoracic>cervical gradient, whereas only one dose of epidural clonidine reduced thermal pain and this was at the thoracic testing site. In contrast, the potency of clonidine to reduce capsaicin-induced allodynia was similar between the two routes of injection, and for hyperalgesia, clonidine was only slightly more potent after intrathecal than epidural injection. These data support clinical studies from non-comparative trials and suggest there is a >6-fold potency ratio of intrathecal:epidural administration of clonidine for acute pain, but a <2-fold potency ratio for these routes for mechanical hypersensitivity.
Pain 2000 Jan
PMID:Relative potency of epidural to intrathecal clonidine differs between acute thermal pain and capsaicin-induced allodynia. 1060 73

It has been demonstrated recently that in addition to its spinal analgesic actions, the alpha 2 adrenoreceptor agonist clonidine also has peripheral analgesic activity. Few data are available regarding the antinociceptive effects of spinal vs peripherally delivered clonidine in inflammatory pain. Thus we have studied spinal (intrathecal = i.t.) and peripheral (intra-articular = i.a.) administration of clonidine in the rat inflamed knee joint model. Thermal and mechanical antinociception was assessed in rats over 28 h using a modified Hargreaves box and von Frey hairs after induction of tonic persistent inflammatory pain by injection of a kaolin-carrageenan mixture into the right knee joint. Thirty minutes after injection of kaolin-carrageenan, clonidine was administered via an i.t. catheter or by i.a. injection into the right inflamed knee joint or by subcutaneous injection (s.c.) (highest effective intra-articular dose). The specific site of action was assessed using the alpha 2 antagonist yohimbine i.t., i.a. or s.c. Clonidine i.t. resulted in thermal and mechanical antinociception during ongoing inflammation, which was not enhanced by inflammation. In contrast, i.a. delivery of clonidine, which also produced a dose-dependent thermal and mechanical antinociceptive effect, revealed a leftward shift in the antinociceptive activity produced by ongoing inflammation. Yohimbine inhibited the antinociceptive action of clonidine at the site of delivery. We suggest that clonidine produces potent thermal and mechanical antinociception regardless of the route of administration. However, chronic inflammatory processing appears to enhance the antinociceptive efficacy of the peripheral alpha 2 agonist.
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PMID:Thermal and mechanical antinociceptive action of spinal vs peripherally administered clonidine in the rat inflamed knee joint model. 1065 15

Both clonidine, an alpha(2) agonist, and morphine, an opioid agonist, provide enhanced patient analgesia after arthroscopic knee surgery when administered via the intraarticular (IA) route. Clonidine potentiates morphine analgesia in the animal model. We designed this study to determine whether clonidine or morphine results in better analgesia and whether their combination would provide superior analgesia to either drug alone. We evaluated 60 patients undergoing arthroscopic knee meniscus repair under local anesthesia with sedation. After surgery, patients were randomized into four IA groups: Group B received 30 mL 0.25% bupivacaine; Group BC received 30 mL 0.25% bupivacaine and clonidine 1 microg/kg; Group BM received 30 mL 0.25% bupivacaine and morphine 3 mg; and Group BCM received 30 mL 0.25% bupivacaine, clonidine 1 microg/kg, and morphine 3 mg. This study revealed a significant benefit from the individual IA administration of both clonidine and morphine. The combination of these drugs resulted in decreased postoperative pain and analgesic use, as well as an increased analgesic duration compared with either drug alone. We conclude that IA clonidine and morphine improved comfort compared with either drug alone in patients undergoing knee arthroscopy.
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PMID:Postoperative analgesia for outpatient arthroscopic knee surgery with intraarticular clonidine and/or morphine. 1115 69

The management of severe pain may require "balanced analgesia," involving the use of analgesics with different modes of action. Clonidine, an alpha(2)-adrenoreceptor agonist produces analgesia by itself as well as when given with morphine and local anesthetics. Ketorolac is indicated for the management of moderately severe acute pain and causes analgesia equivalent to morphine. This study was designed to investigate whether the addition of ketorolac promotes antinociception produced by intrathecal administration of clonidine in male Sprague-Dawley rats. Intrathecal injection of clonidine (1-30 microg) induced a dose-dependent increase in antinociception as measured by the tail flick (TF) and hot plate tests. Ketorolac alone (150-600 microg) increased the antinociception by 50%-60% only in the TF test. Ketorolac (10 microg) decreased clonidine (10 microg)-induced antinociception from 69.1% +/- 7.8% to 23.5% +/- 1. 6% (P < 0.05) in the TF test and 35.7% +/- 4.7% to 4.5% +/- 0.1% (P < 0.05) maximum possible effect in the hot plate test. Ketorolac also antagonized the effect of 30 microg of clonidine. The opioid receptor antagonist naloxone antagonized the antinociceptive effect of clonidine and ketorolac, indicating the involvement of the opioid system in the antinociception produced by clonidine or ketorolac. However, neither clonidine nor ketorolac (10(-8) to 10(-3) M) inhibited the binding of specific ligands to mu-, delta-, and kappa-opioid receptors, indicating a lack of direct interaction of clonidine and ketorolac with opioid receptors. These results suggest that intrathecal injection of ketorolac antagonizes the antinociception produced by clonidine.
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PMID:Antagonism of antinociception produced by intrathecal clonidine by ketorolac in the rat: the role of the opioid system. 1078 70

The effects of agmatine, which is an endogenous polyamine metabolite formed by decarboxylation of L-arginine, and a combination of agmatine and morphine on tail-flick test have been investigated in mice. Adult male Swiss-Webster mice were used in the study. Agmatine (10, 20 and 40 mg/kg), clonidine (0.15 mg/kg), yohimbine (0.625 and 1.25 mg/kg), or saline were injected into mice intraperitoneally. Morphine (1 and 2 mg/kg) was given subcutaneously. Agmatine alone did not produce any significant change on radiant tail-flick latencies, but it potentiated significantly and dose-dependently morphine-induced (1 mg/kg) analgesia. The potentiating effect of agmatine (40 mg/kg) on morphine-induced analgesia was blocked completely by yohimbine (0.625 mg/kg), a selective alpha(2)-adrenoceptor antagonist, pretreatment. Clonidine (0.15 mg/kg), an alpha(2-)adrenergic receptor agonist, caused a significant increase of the tail-flick latencies of the mice. Yohimbine (0.625 mg/kg) also blocked clonidine-induced analgesia. In addition, yohimbine (0.625 mg/kg) was ineffective on the tail-flick test and did not produce any significant change on the morphine-induced analgesia. Our results indicate that cotreatment of agmatine with morphine produces antinociceptive enhancement via an alpha(2-)adrenergic receptor-mediated mechanism and agmatine-morphine combination may be an effective therapeutic strategy for medical treatment of pain.
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PMID:Agmatine potentiates the analgesic effect of morphine by an alpha(2)-adrenoceptor-mediated mechanism in mice. 1137 23

To characterize alpha(2)-adrenergic control of motor and sensory functions of gastrointestinal tract and colon, we studied dose-related effects of clonidine (placebo or up to 0.3 mg po) by random assignment in 55 healthy humans. Gastrointestinal transit was measured in all subjects; in 35, we assessed colonic compliance, tone, and sensations of gas and pain during phasic distensions. Clonidine did not significantly alter gastrointestinal or colonic transit, but it increased colonic compliance and reduced fasting tone without altering colonic response to a meal. Clonidine significantly reduced aggregate sensation to distensions overall and had significant linear dose-related sensory effects at 8- and 24-mmHg distensions. Effect on pain (including dose-response relationship) was due to 0.3-mg dose for distensions at 24 mmHg. We confirmed that clonidine relaxes fasting colonic tone and reduces sensation of pain. In this study, gut transit was not altered by clonidine, and novel dose-response characteristics and clonidine's effect on gas sensation are provided. Doses as low as 0.05 mg may be effective and potentially useful in reducing colonic tone and gas sensation.
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PMID:Effects of an alpha(2)-adrenergic agonist on gastrointestinal transit, colonic motility, and sensation in humans. 1170 52

The aim of this double-blind randomized study was to evaluate the optimal intravenous dose of clonidine administrated during the peri-operative period, after lumbar hemilaminectomy for herniated disk repair. The "optimal intravenous dose" was defined as that providing minimal analgesic request, stable haemodynamic profile and a minimal sedation score during 12h after extubation. Eighty adult patients, ASA physical status I-II, undergoing lumbar hemilaminectomy for herniated disk (L(4)-L(5), L(5)-S(1)) were included in the study. All the patients were randomly assigned to one of four study groups (A, B, C, D), 20 patients each. The same standardized general anaesthesia was performed for each group. Thirty minutes before the end of surgery, group A, B and C patients received three different loading doses of intravenous clonidine (5 microg/kg, 3 microg/kg, 2 microg/kg respectively), followed by the same infusion of intravenous clonidine (0.3 microg/kg per hour). Group D patients received a bolus dose and a continuous infusion of NaCl 0.9%. In the recovery unit, postoperative pain was treated by a patient-controlled analgesia device, containing morphine. Pain relief was evaluated by the total morphine requirement during the postoperative period. Systolic blood pressure (SBP), heart rate and sedation were also noted during the first 12h postoperatively. Intravenous clonidine decreased morphine requirements in a dose-dependent manner. Group A, B, C and D patients requested 5 +/- 2, 11 +/- 3, 19 +/- 4 and 29 +/- 8 doses of morphine respectively. Clonidine also affected SBP in a dose-related manner. Group A, B and C patients had an SBP decrease respectively of 26 +/- 3%, 7 +/- 4% and 2 +/- 2% compared with basic values while, at the same time, in group D patients no SBP variation was registered. In conclusion, this study demonstrates that, when sedation and analgesic effect of clonidine is required, 3 microg/kg bolus dose followed by a continuous infusion of 0.3 microg/kg per hour has to be considered the optimal intravenous dose. The higher dose of intravenous clonidine (5 microg/kg) produced better analgesia but the degree of hypotension and sedation was more severe and longer lasting; it required ephedrine administration and careful monitoring of the patient. On the other hand, the bolus of intravenous clonidine 2 microg/kg (group C) was less effective in terms of pain relief but with similar side-effects to the 3 microg/kg dosage (group B).
Eur J Pain 2002
PMID:Clonidine for treatment of postoperative pain: a dose-finding study. 1188 26

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