Biomedical subjects

J A Desmeules

Publications and source records attributed to J A Desmeules.

11 recordsLinked to original sources

PubMed2005

Systemic allergic reaction and diffuse bone pain after exposure to a preparation of betamethasone.

Allergic reactions to corticosteroids are unexpected as they seem to contradict their pharmacodynamic action. Nevertheless, they are not infrequent, with an estimated incidence of up to 4% for cutaneous reactions. Systemic reactions are rarely reported, but their incidence might be underestimated. We report here an unusual allergic reaction to betamethasone presenting with diffuse bone pain, erythema, and bronchoconstriction, which was confirmed by a positive rechallenge in a double-blind procedure. This is the first case report of a systemic reaction to betamethasone confirmed by a positive rechallenge. An impurity in betamethasone diproprionate cannot be excluded. As this substance is frequently used in rheumatologic soft-tissue injections, it is important to recognize this potentially life-threatening side effect.

Journal Article↗

PubMed2003

Neurophysiologic evidence for a central sensitization in patients with fibromyalgia.

OBJECTIVE: To determine whether abnormalities of peripheral and central nociceptive sensory input processing exist outside areas of spontaneous pain in patients with fibromyalgia (FM) as compared with controls, by using quantitative sensory testing (QST) and a neurophysiologic paradigm independent from subjective reports. METHODS: A total of 164 outpatients with FM who were attending a self-management program were invited to participate in the study. Data for 85 patients were available and were compared with those for 40 non-FM controls matched for age and sex. QST was performed using thermal, mechanical, and electrical stimuli at locations of nonspontaneous pain. Pain assessment was 2-fold and included use of subjective scales and the spinal nociceptive flexion reflex (NFR), a specific physiologic correlate for the objective evaluation of central nociceptive pathways. Questionnaires regarding quality of life and the impact of FM were available. RESULTS: Participants were mainly middle-aged women, with a mean disease duration of 8 years. Between-group differences were significant for neurophysiologic, clinical, and quality of life measures. In patients with FM, peripheral QST showed significantly altered cold and heat pain thresholds, and tolerance to cold pain was radically reduced. The median NFR threshold in patients with FM (22.7 mA [range 17.5-31.7]) was significantly decreased compared with that in controls (33 mA [range 28.1-41]). A cutoff value of <27.6 mA for NFR provided sensitivity of 73% and specificity of 80% for detecting central allodynia in the setting of FM. CONCLUSION: Our results strongly, although indirectly, point to a state of central hyperexcitability of the nociceptive system in patients with FM. The NFR can be used to assess central allodynia in FM. It may also help discriminate patients who may benefit from use of centrally acting analgesics.

Female↗

PubMed2002

Advances with analgesics and NSAIDs for the treatment of spinal disorders.

One of the major developments with regard to chronic non-malignant pain in these last few years has been a better understanding of the mechanisms that act to maintain pain, while inferences about the pathophysiology have facilitated therapeutic decision-making. This chapter reviews the strength of evidence for the therapeutic effect of pharmacological symptomatic approaches using non-steroidal anti-inflammatory agents, opioids and co-analgesics in acute and chronic back pain with an emphasis on the results of randomized controlled trials as well as on the need for long-term comparative trials of drug efficacy, toxicity and compliance.

Acute Disease↗

PubMed2000

The tramadol option.

Tramadol is an option for the treatment of rheumatological pain. Its mode of action and safety profile distinguishes it from other opioids. Tramadol differs from other opioids by combining a weak opioid and a monoaminergic mode of action. It is effective in different types of moderate-to-severe pain, including neuropathic pain. Moreover, as the mode of action of tramadol does not overlap with that of NSAIDs, it is a useful agent to be combined with these drugs. Tramadol induces fewer opioid adverse reactions for a given level of analgesia compared with traditional opioids. Common adverse reactions of tramadol such as nausea and dizziness, which usually occur only at the beginning of therapy and attenuate over time, can be further minimized by up-titrating the drug over several days. Dose adjustment is only necessary in patients over 75 years of age, or in those with either hepatic or renal insufficiency. Tramadol should be avoided or used with caution in epileptics, or in individuals who are receiving seizure-threshold lowering drugs. Finally, tramadol has a low risk of abuse because it has only a weak opioid effect and its monoaminergic action could inhibit the development of dependence. The low abuse potential of tramadol has been demonstrated by postmarketing surveillance data.

Analgesics, Opioid↗

PubMed1999

Contribution of cytochrome P-4502D6 phenotype to the neuromodulatory effects of dextromethorphan.

Dextromethorphan (DEM)-mediated N-methyl-D-aspartate receptor blockade may result from an action of unchanged DEM or its active metabolite, dextrorphan (DOR). In humans, DEM is metabolized into DOR by the polymorphic enzyme CYP2D6. We therefore investigated the impact of quinidine (Qd), a selective inhibitor of CYP2D6, on DEM disposition and the contribution of CYP2D6 phenotype on DEM antinociceptive and neuromodulatory effects. Using a randomized, double-blind, crossover, placebo-controlled design, healthy volunteers (n = 7) received Qd (50 mg Qd sulfate orally) or a placebo and, 12 h later, either DEM (50 mg DEM hydrobromide orally) or a placebo. DEM and DOR pharmacodynamics were assessed for their antinociceptive and neuromodulatory effects. Antinociceptive effects were assessed over 4 h by subjective pain threshold and RIII nociceptive reflex (RIII) monitoring. Neuromodulatory effects were studied using the primary and secondary hyperalgesia induced by the topical application of capsaicin. Two of seven subjects were genotypic CYP2D6 PM. Pretreatment of EM by Qd suppressed DOR formation and increased the plasma level of DEM to the levels of poor metabolizers. In poor metabolizers, DEM induced a significant increase in objective (+45%) and subjective (+35%) pain thresholds. In extensive metabolizers, only a slight and short-lasting increase in the subjective threshold was observed, whereas no effect was seen on the objective threshold. DEM modulates secondary hyperalgesia compared with DOR. The CYP2D6 phenotype affects the disposition of DEM and the production of the active metabolite DOR. The impact of the CYP2D6 phenotype is of major importance for the spinal antinociceptive and neuromodulatory effects of DEM.

Adult↗

PubMed1996

Contribution of monoaminergic modulation to the analgesic effect of tramadol.

1. In humans, the central analgesic effect of tramadol 100 mg orally is only partially reversed by the opioid antagonist naloxone (0.8 mg intravenously). As suggested by in vitro and animal data tramadol analgesia may thus result from an action on opioid as well as monoaminergic pathways. We therefore investigated the effect of alpha 2-adrenoceptor antagonism with yohimbine on tramadol analgesia. 2. Healthy volunteers (n = 10) received tramadol (100 mg orally), followed (+3 h) by yohimbine (0.1 mg kg-1 intravenously), and yohimbine + naloxone (0.8 mg intravenously) and their respective placebo according to a randomized, double-blind crossover, placebo (P) controlled design. Analgesia was assessed over 8 h by subjective pain threshold (pain intensity numerical scale--PINS) and objective pain threshold (RIII nociceptive reflex--RIII) monitoring. 3. Tramadol induced a significant increase in both pain thresholds. Peak analgesic effect was observed at 3.7 h (RIII + 39.6 +/- 3.9% and PINS 50.1 +/- s.e.mean 5%) and the analgesia lasted about 6 h. 4. Yohimbine significantly reversed the analgesic effects of tramadol for 2.8 h with a maximum decrease of 97 +/- 4% (RIII) and 67 +/- 12% (PINS), whereas the addition of naloxone abolished tramadol effects throughout the study period with a decrease of 90 +/- 6% (RIII) and 79 +/- 9% (PINS), P < 0.05). 5. Yohimbine alone did not significantly reduce pain thresholds. 6. alpha 2-Adrenoceptor antagonism reverses tramadol effects, thus pointing to the significant role of monoaminergic modulation and the synergy with opioid agonism in tramadol antinociception after a single oral dose.

Adrenergic alpha-Antagonists↗

PubMed1995

Influence of the sympathetic nervous system in the development of abnormal pain-related behaviours in a rat model of neuropathic pain.

This study evaluated the effect of surgical sympathectomy on pain-related behaviours in a well established model of peripheral mononeuropathy produced by loose ligatures around the common sciatic nerve in the rat. Behavioural abnormalities include spontaneous abnormal position of the hindpaw after the nerve constriction, indicative of "spontaneous pain", and changes in responses to mechanical or thermal stimuli applied to this paw. These changes are usually maximal at week 2 after the surgery, stable until weeks 3-4, and disappear between weeks 8 and 12. To assess the role of the sympathetic nervous system in the development and persistence of these abnormalities, four groups of rats were behaviourally tested: (i) rats receiving a complete sham surgery, (ii) rats with a sciatic nerve constriction produced by loose ligatures around the common nerve trunk plus a sham sympathectomy, (iii) rats receiving a lumbar sympathectomy with a sham nerve ligature, and (iv) rats receiving a simultaneous surgical lumbar sympathectomy and a sciatic nerve constriction. The efficacy of the sympathectomy was assessed by the measure of the noradrenaline level in the sciatic nerve. Sympathectomy reduced selectively or even prevented the abnormal reaction to cold temperature and to heat (45 degrees C) in rats with a peripheral mononeuropathy. In contrast, the abnormal reaction to mechanical pressure was not influenced, and the behavioural abnormalities indicating spontaneous pain were still present. Sympathectomy alone resulted in a reduction of the vocalization threshold to pressure on both hindpaws, but also a short-lasting increased tolerance to cold immersion. This study confirms the selective role of the sympathetic nervous system in affecting the development and maintenance of some abnormal pain-related behaviours to thermal stimuli in rats with a moderate, but persistent, constriction of one sciatic nerve.

Animals↗

PubMed1994

[Which analgesic dosage of paracetamol?].

The purpose of this study was to evaluate the dose-response of paracetamol and to assess its plasma concentration-effect relationship. According to a randomized, double-blind, and placebo controlled design healthy volunteers (n = 11) received 0.5, 1 and 2 g paracetamol (as propacetamol) intravenously (15 min). The extent of analgesic effect was measured over 8 hours by objective pain threshold (R-III) monitoring after selective transcutaneous electrical stimulation of the ipsilateral sural nerve. Maximal R-III threshold increase is at 2 hours after 0.5 g and 2.5 hours after 1 g and 2 g. The delayed peak effects, when compared to peak plasma concentrations, draw counter clockwise hysteresis. Duration of paracetamol antinociceptive effect increased concomitantly to dosage increment. Intravenous paracetamol exerts a dose-dependent central analgesia.

Acetaminophen↗

PubMed1993

The highly selective delta agonist BUBU induces an analgesic effect in normal and arthritic rat and this action is not affected by repeated administration of low doses of morphine.

The effect of various doses of the selective delta agonist BUBU (Tyr-D-Ser(O-t-butyl)-Gly-Phe-Leu-Thr(O-t-butyl) on the vocalization threshold to paw pressure were compared in normal and arthritic rats, a suitable clinical model of chronic pain. In both group of rats, the intravenous administration of BUBU (6, 9, 12 mg/kg in normal and 1.5, 3, 6 mg/kg in arthritic rats) led to significant antinociceptive effects. The same dose of BUBU (6 mg/kg i.v.) produced a much more potent antinociceptive effect in arthritic than in normal rats, and a dose as low as 1.5 mg/kg produced a significant analgesic effect in the arthritic animal, whereas at 3 mg/kg BUBU was ineffective in normal rats. The analgesic effects of BUBU (9 mg/kg in normal and 3 mg/kg in arthritic rats) were completely prevented by the selective delta antagonist naltrindole (1 mg/kg i.v. a dose devoid of analgesic potency per se), while they were not affected by the selective mu antagonist naloxone (0.05 mg/kg i.v.). In addition, 3 mg/kg i.v. of BUBU remained effective in morphine tolerant arthritic rats. These results suggest that delta opioid receptor activation can modulate the transmission of cutaneous mechanical nociceptive information in rats, especially in inflammatory pain conditions.

Analgesics↗

PubMed1993

Opposite effects of axon damage on heat shock proteins (hsp 70) and ubiquitin contents in motor neurons of neuropathic rats.

Alteration in the motoneurone contents of heat shock protein (hsp 70) and ubiquitin were studied in rats which had been subject to loose ligation of one common sciatic nerve. This results in a unilateral peripheral neuropathy which peaks at 14 days following ligation and is characterized by transient degeneration of both myelinated and unmyelinated nerve fibres, abnormal motor behaviours (posture of the hind limb, walking patterns) and thermal and mechanical allodynia of the hind paw. Hsp 70 and ubiquitin are proteins involved in protein metabolism and their expression is regulated during cellular stress. The contralateral unlesioned side was used as control. Motoneurone staining for hsp 70 and ubiquitin were differentially altered at the peak of the neuropathy. Axon damage resulted in a decrease in hsp 70 labeling while ubiquitin staining increased. At the same time motoneurones undergoing axon damage overstained for the immediate early gene encoded protein c-JUN and for nerve growth factor receptor (rNGF). In contrast, no clear alteration was seen, at that time, in the intensity of labeling for calcitonin gene-related peptide (CGRP). This study demonstrates that peripheral neuropathy resulting from loose ligation of the common sciatic nerve not only produces sensory alterations as previously reported but also leads to pronounced alterations in motoneurone functioning that could partly explain the observed abnormal motor behaviours. Results are discussed in accordance with presumed roles for hsp 70 and ubiquitin in protein metabolism and in relationship with possible interaction with c-JUN and rNGF expressions.

Animals↗

PubMed1993

Selective opioid receptor agonists modulate mechanical allodynia in an animal model of neuropathic pain.

This study evaluated the antinociceptive effects of systemically administered selective opioid agonists of mu (DAMGO), delta (BUBU) and kappa (U 69593) receptors on the vocalization threshold to paw pressure in a rat model of peripheral unilateral mononeuropathy produced by loose ligatures around the common sciatic nerve. DAMGO (0.5-2 mg/kg), BUBU (1.5-6 mg/kg) and U 69593 (0.75-3 mg/kg) injected intravenously (i.v.) produced a potent long-lasting antinociceptive effect on both hind paws. The effects on the lesioned paw were clearly and statistically more potent than for the non-lesioned paw. The selective antinociceptive effect of 2 mg/kg DAMGO, 3 mg/kg BUBU and 1.5 mg/kg U 69593 were completely prevented by prior administration of the appropriate antagonists: 0.1 mg/kg naloxone, 1 mg/kg naltrindole and 0.4 mg/kg MR 2266. The present data clearly show that an acute i.v. injection of these selective opioid agonists induces potent antinociceptive effects in a rat model of peripheral neuropathy. These data are discussed with regard to the classical view that there is opioid resistance in neuropathic pain.

Analgesics↗