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

Antagonists of NMDA glutamate receptors have been shown to alleviate neuropathic pain in rats and humans. However, NMDA antagonists can cause significant side effects ranging from behavioral disturbances to injury of neurons in the posterior cingulate/retrosplenial (PC/RS) cortex. We have found that alpha-2 adrenergic agonists prevent the PC/RS neurotoxic side effects of NMDA antagonists. In the present study of adult female rats subjected to sciatic nerve ligation (Bennett neuropathic pain model) and tested for paw withdrawal latency (PWL) following a thermal stimulus, we evaluated the ability of the NMDA antagonist, MK-801, to alleviate neuropathic pain either by itself or when administered together with the alpha-2 adrenergic agonist, clonidine. We found that MK-801, at a dose (0.05 mg/kg s.c.) that is known to cause mild hyperactivity but is subthreshold for producing PC/RS neurotoxic changes, relieved the neuropathic pain state associated with sciatic nerve ligation. However, the relief at this dose was very transient, and no neuropathic pain-relieving effect was observed at a lower dose (0. 025 mg/kg s.c.) of MK-801. Clonidine, at a dose (0.05 mg/kg s.c.) that prevents the cerebrocortical neurotoxic effects of MK-801, decreased sensitivity to the thermal stimulus equally under all conditions (ligated, sham ligated, unoperated), but did not specifically relieve neuropathic pain in the ligated limb. Combining this dose of clonidine with an ineffective dose (0.025 mg/kg s.c.) of MK-801 provided specific, complete and long lasting (up to 4 h) relief from neuropathic pain. Rats receiving this drug combination did not display hyperactivity or any other behavioral disturbance typically associated with MK-801 treatment, nor show neurotoxic changes in cerebrocortical neurons. In separate experiments on normal unoperated rats, we found that clonidine (0.05 mg/kg s.c.) counteracted the hyperactivity induced by MK-801 (0.05 mg/kg s.c.) and returned activity levels to a normal range. These findings signify that clonidine, which does not specifically relieve neuropathic pain, can potentiate the neuropathic pain-relieving action of MK-801, while also protecting against neurotoxicity and hyperactivity side effects of MK-801. The potentiation is of a sufficient magnitude that it permits cutting the MK-801 dose requirement in half, thereby achieving prolonged neuropathic pain relief while doubling the margin of safety against any type of side effect that might be mediated by blockade of NMDA receptors.
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PMID:Clonidine potentiates the neuropathic pain-relieving action of MK-801 while preventing its neurotoxic and hyperactivity side effects. 950 31

A cold plate apparatus was designed to test the responses of unrestrained rats to low temperature stimulation of the plantar aspect of the paw. At plate temperatures of 10 degrees C and 5 degrees C, rats with either chronic constriction injury (CCI) of the sciatic nerve or complete Freund's adjuvant (CFA) induced inflammation of the hindpaw displayed a stereotyped behavior. Brisk lifts of the treated hindpaw were recorded, while no evidence of other nociceptive behaviors could be discerned. The most consistent responses were obtained with a plate temperature of 5 degrees C in three 5-min testing periods, separated by 10-min intervals during which the animals were returned to a normal environment. Concomitantly to cold testing, the rats were evaluated for their response to heat (plantar test) and mechanical (von Frey hairs) stimuli. In both injury models, while responses to heat stimuli had normalized at 60 days post-injury, a clear lateralization of responses to cold was observed throughout the entire study period. Systemic lidocaine, clonidine, and morphine suppressed responses to cold in a dose-related fashion. At doses that did not affect motor or sensory behavior, both lidocaine and its quaternary derivative QX-314 similarly reduced paw lifts, suggesting that cold hyperalgesia is in part due to peripheral altered nociceptive processing. Clonidine was more potent in CCI then in CFA rats in reducing the response to cold. Paradoxically, clonidine increased the withdrawal latencies to heat in the CCI hindpaw at 40 days and thereafter, at a time when both hindpaws had the same withdrawal latencies in control animals. Morphine was also more potent on CCI than CFA cold responses, indicating that, chronically, CFA-induced hyperalgesia might be opiate resistant. Evidence for tonic endogenous inhibition of cold hyperalgesia was obtained for CFA rats, when systemic naltrexone significantly increased the number of paw lifts; this was not found in rats with CCI. At 60 days, neither morphine nor naltrexone affected cold-induced paw lifting in CFA rats, suggesting that the neuronal circuit mediating cold hyperalgesia in these animals had become opiate insensitive. In conclusion, the cold plate was found to be a reliable method for detecting abnormal nociceptive behavior even at long intervals after nerve or inflammatory injuries, when responses to other nociceptive stimuli have returned to near normal. The results of pharmacological studies suggest that cold hyperalgesia is in part a consequence of altered sensory processing in the periphery, and that it can be independently modulated by opiate and adrenergic systems.
Pain 1998 Apr
PMID:The cold plate as a test of nociceptive behaviors: description and application to the study of chronic neuropathic and inflammatory pain models. 958 73

An open-label trial of clonidine, an alpha 2-adrenergic agonist, was prescribed for patients with a clinical diagnosis of oral neuropathic pain or neuralgia involving the oral cavity. Clonidine (0.2 mg/g) was prepared in a cream base and applied four times daily to the site of pain. Seventeen patients were assessed: 10 were diagnosed with neuropathic pain, and 7 with neuralgia. Two of the 17 patients had complaints overlapping both neuropathic and neuralgic pain. In the patients with neuropathic pain, an overall mean reduction in severity of burning of 36% (on a 10-point visual analogue scale) was reported. Half of these patients reported clinical improvement; however, no patients reported complete resolution of symptoms. Of the patients with characteristics of neuralgia, 57% improved; and in those who reported improvement, a mean reduction of approximately 54% was reported. In the 4 patients with neuralgia who responded, a 94% reduction in pain was reported, with complete resolution of pain in 2 patients. This open-label clinical trial suggests that topical clonidine may be effective in the management of some patients with oral neuralgia-like pain, but may have a more limited effect in those patients with oral neuropathic pain. Besides type of pain, no other variables predicted which of the patients would achieve pain reduction with topical clonidine. Although confirmation of clinical efficacy requires double-blind clinical studies, this initial trial suggests that further study is warranted.
J Orofac Pain 1997
PMID:Topical clonidine for orofacial pain: a pilot study. 965 11

Clonidine is an alpha 2-adrenoceptor agonist which has been used for over 20 years to treat hypertension. It has recently, however, found a new and possibly significant role in anaesthesia and the treatment of pain. This article discusses the premedicant, perioperative and postoperative uses of clonidine.
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PMID:The role of clonidine in anaesthesia. 972 50

Clonidine is a selective alpha 2 adrenergic receptors agonist with a wide spectrum of activity. Except well known hypotensive effect, clonidine stabilizes circulatory system and has sedative, anxiolytic, analgesic, diuretic etc. activities. Clonidine has some appliance during perioperative period. When used in premedication it has a lot of advantages: causes sedation, has anxiolytic properties, reduces secretion of saliva, stabilizes circulatory system, diminishes stress reaction, augments action of anaesthetic and analgesic drugs. When used during the operation, regulates circulatory system, prolongs and amplifies central and peripheral blocks. Clonidine diminishes patients requirement for opioids and local anaesthetics during postoperative and long-term pain therapy.
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PMID:[Use of clonidine for perioperative therapy]. 974 Nov 98

Clonidine has both analgesic and sedative actions, and it has been used in a variety of settings as a sedative, or both. We administered oral clonidine with intravenous ketamine to a burn patient to control severe pain. Clonidine produced good analgesia and sedation. In addition, clonidine counterbalanced the sympathetic stimulation of ketamine by virtue of its action in reducing sympathetic outflow. The combination of these two drugs may be useful for burn patients with hypertension or myocardial ischemia.
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PMID:Oral clonidine for sedation and analgesia in a burn patient. 979 19

Clonidine, an alpha2 adrenoceptor agonist, has anti-hypertensive and anti-nociceptive effects. It is commonly used in association with local anaesthetics and opioids to enhance the quality and duration of extradural analgesia in the postoperative period, and to decrease the incidence of side effects. As a sole analgesic, it has seldom been used to relieve postoperative pain. The dose of extradural clonidine to achieve good pain relief without deleterious side effects remains undetermined. In order to address this problem, we performed a computer search via two well-known databases, Medline and Excerpta Medica, covering the period from 1985 to September 1997. One hundred and fifty-nine articles were retrieved of which 38 dealt with extradural clonidine and postoperative pain. All but 16 studies suffered from serious design flaws, such as lack of controls and/or randomization, or inadequate statistical analysis. The data from these studies were difficult to interpret because of the tremendous variation in variables, especially dose of clonidine, level of extradural injection, time of administration, type of anaesthesia, type of surgery, and reference and rescue drugs. The simultaneous extradural use of local anaesthetics and opioids further hindered data interpretation, and precluded any meta-analysis. Proposals for a standard study design are made to help comparison between studies involving extradural clonidine and postoperative pain.
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PMID:Meta-analysis of the efficacy of extradural clonidine to relieve postoperative pain: an impossible task. 981 9

Epidural analgesia and spinal analgesia are the most effective techniques for relieving labour pain. Basically, local anaesthetics (i.e. bupivacaine) and opioids (i.e. fentanyl or sufentanil), especially when combined, produce excellent analgesia with minimal motor blockade. However, none of these agents is devoid of side-effects and analgesia remains sometimes imperfect, suggesting that new drugs would be welcome. Adrenalin and clonidine act on a2-adrenoceptors in the spinal cord and both have been found to improve analgesia. These two drugs have already been used in many patients and studies because the absence of neurotoxicity has been well documented. Clonidine looks more attractive, although sedation and hypotension limit its use. Other analgesic drugs are promising alternatives but are still at an experimental or very early clinical stage. Neostigmine and ketamine (without preservative) are not neurotoxic while midazolam neurotoxicity is still controversial. Intravenous remifentanil might prove useful when neuraxial analgesia is contraindicated.
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PMID:Promising non-narcotic analgesic techniques for labour. 1002 28

Clonidine Hydrochloride Injection (Duraclon) is a clear, colorless, preservative-free, pyrogen free, aqueous solution of clonidine hydrochloride. The indication for this product is for use as an adjunct in pain management, administered epidurally, when opiates are insufficient. The drug formulation was evaluated under both normal and stress conditions in the preformulation/formulation studies. The list of studies conducted includes a light sensitivity study, an oxygen sensitivity study, a pH/stability study, a stopper compatibility evaluation, a freeze-thaw study, and a stability study. Samples from the light, oxygen, pH/stability, and stability studies were evaluated for color, visual clarity, pH, potency, and chromatographic purity. Samples from the freeze-thaw study were evaluated for all of the above except chromatographic purity. The results for these studies demonstrate the stability of the product as formulated. The pH of this unbuffered product was consistently within the acceptance criteria. The product remained clear and colorless for the duration of each study. The values obtained for the potency and chromatographic purity assays showed no evidence of degradation. The reasons for the lack of degradation can be found in the molecular structure of the drug substance and the formulation of the drug product. Since the molecular structure is that of a Schiff base, it is theoretically possible, although difficult, to cleave the molecule. A catalyst would be required, and none of the possible catalysts are present in the formulation. The molecule could also be cleaved upon exposure to light, and the evidence indicates that the molecule does interact with light. This interaction is not to the degree, however, that product stability is affected. The formulation contains only the active drug substance and sodium chloride in water for injection with a pH of approximately 6. Although the product is unbuffered, the influence of the stoppers and glass vials upon the formulation pH was minimal. In addition, the stopper compatibility of the product is enhanced by the absence of chelating agents, preservatives, acids, and bases. Since the dilute concentrations of both the active and excipient are well below their solubility limits, no solubility related issues would be expected upon freezing and subsequent thawing. Clonidine Hydrochloride Injection, as formulated, does not require protection from light, oxygen, or freezing. The product shows acceptable stability within the pH range, and the rubber closure is compatible with the product. Real time stability data combined with statistical projections support a 36-month expiration date.
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PMID:Formulation of a stable parenteral product; Clonidine Hydrochloride Injection. 1005 Jan 30

The effect of noradrenaline on the glycine response was investigated in neurons acutely dissociated from the rat sacral dorsal commissural nucleus using nystatin perforated patch recording configuration under voltage-clamp conditions. Noradrenaline reversibly potentiated the 10(-5)M glycine-induced Cl- current in a concentration-dependent manner. Single channel recordings in a cell-attached mode revealed that noradrenaline decreased the closing time of the glycine-activated channel activity. Noradrenaline neither changed the reversal potential of the glycine response nor affected the affinity of glycine to its receptor. Clonidine mimicked and yohimbine blocked the noradrenaline action on glycine response. N-[2(methylamino)ethyl]-5-isoquinoline sulfonamide dihydrochloride, protein kinase A inhibitor, mimicked the effect of noradrenaline on glycine response. Noradrenaline failed to affect the glycine response in the presence of these intracellular cyclic AMP and protein kinase A modulators. However, noradrenaline further enhanced the glycine response even in the presence of phorbol-12-myristate-13-acetate and chelerythrine, a protein kinase C inhibitor. Pertussis toxin treatment for 6-8 h blocked the noradrenaline facilitatory effect on the glycine response. In addition, noradrenaline potentiated the strychnine-sensitive postsynaptic currents evoked in a slice preparation of sacral dorsal commissural nucleus. These results suggest that the activation of alpha2-adrenoceptor by noradrenaline coupled with pertussis toxin-sensitive G-proteins reduces intracellular cyclic AMP formation through the inhibition of adenyl cyclase. The reduction of cyclic AMP decreases the protein kinase A activity, thus resulting in the potentiation of the glycinergic inputs to the sacral dorsal commissural neurons. It is thus feasible that the noradrenergic input to the sacral dorsal commissural nucleus modulates such nociceptive signals as pain by intracellular enhancing the glycine response.
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PMID:Alpha2-adrenoceptor-mediated enhancement of glycine response in rat sacral dorsal commissural neurons. 1005 Dec 15


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