Preoperative Anxiolytic Effect of Melatonin and Clonidine on Postoperative Pain and Morphine Consumption in Patients Undergoing Abdominal Hysterectomy: A Double-Blind, Randomized, Placebo-Controlled Study

Anesthesia Service and Perioperative Medicine, Hospital de CLíNICAS DE Porto Alegre/Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
The journal of pain: official journal of the American Pain Society (Impact Factor: 4.01). 12/2008; 10(1):100-8. DOI: 10.1016/j.jpain.2008.08.007
Source: PubMed


Recent evidence has demonstrated analgesic, anti-inflammatory, and anxiolytic properties of melatonin. Taking into account that higher anxiety makes the control of postoperative pain more difficult, one can hypothesize that melatonin anxiolytic and analgesic effects improve the control of postoperative pain. Thus, we conducted a randomized, double-blind, placebo-controlled study with 59 patients undergoing abdominal hysterectomy to test the hypothesis that melatonin is as effective as clonidine and that both are more effective than placebo in reducing postoperative pain. Additionally, we compared their anxiolytic effects on postoperative pain. Patients were randomly assigned to receive oral melatonin (5 mg) (n = 20), clonidine (100 microg) (n = 19), or placebo (n = 20) orally. In addition to primary outcomes of pain intensity and analgesic consumption, secondary outcome measures included postoperative state anxiety. In anxious patients 6 hours after surgery, the number of patients needed to be to prevent moderate to intense pain during the first 24 hours after surgery was 1.52 (95% CI, 1.14 to 6.02) and 1.64 (95% CI, 1.29 to 5.93), respectively, in the melatonin and clonidine groups compared with placebo. Also, the anxiolytic effect of melatonin and clonidine resulted in reduced postoperative morphine consumption by more than 30%. However, in the mildly anxious, it was not observed the treatment effect on pain. PERSPECTIVES: The preoperative anxiolysis with melatonin or clonidine reduced postoperative pain and morphine consumption in patients undergoing abdominal hysterectomy. The effects these 2 drugs were equivalent and greater than with placebo.

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Available from: Rosa Levandovski, Jun 24, 2014
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    • "Melatonin’s effect on pain has been demonstrated in animals for inflammatory [8] and neuropathic pain [11-13], as well in acute [10,14] and chronic pain in humans [15,16]. In addition, there is some clinical evidence of melatonin’s effect on FM [5,6]. "
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    ABSTRACT: Central disinhibition is a mechanism involved in the physiopathology of fibromyalgia. Melatonin can improve sleep quality, pain and pain threshold. We hypothesized that treatment with melatonin alone or in combination with amitriptyline would be superior to amitriptyline alone in modifying the endogenous pain-modulating system (PMS) as quantified by conditional pain modulation (CPM), and this change in CPM could be associated with serum brain-derived neurotrophic factor (BDNF). We also tested whether melatonin improves the clinical symptoms of pain, pain threshold and sleep quality. Sixty-three females, aged 18 to 65, were randomized to receive bedtime amitriptyline (25 mg) (n = 21), melatonin (10 mg) (n = 21) or melatonin (10 mg) + amitriptyline (25 mg) (n = 21) for a period of six weeks. The descending PMS was assessed with the CPM-TASK. It was assessed the pain score on the Visual Analog Scale (VAS 0-100 mm), the score on Fibromyalgia Impact Questionnaire (FIQ), heat pain threshold (HPT), sleep quality and BDNF serum. Delta values (post- minus pre-treatment) were used to compare the treatment effect. The outcomes variables were collected before, one and six weeks after initiating treatment. Melatonin alone or in combination with amitriptyline reduced significantly pain on the VAS compared with amitriptyline alone (P < 0.01). The delta values on the VAS scores were-12.85 (19.93),-17.37 (18.69) and-20.93 (12.23) in the amitriptyline, melatonin and melatonin+amitriptyline groups, respectively. Melatonin alone and in combination increased the inhibitory PMS as assessed by the Numerical Pain Scale [NPS(0-10)] reduction during the CPM-TASK:-2.4 (2.04) melatonin + amitriptyline,-2.65 (1.68) melatonin, and-1.04 (2.06) amitriptyline, (P < 0.05). Melatonin + amitriptyline treated displayed better results than melatonin and amitriptyline alone in terms of FIQ and PPT improvement (P < 0.05, fort both). Melatonin increased the inhibitory endogenous pain-modulating system as assessed by the reduction on NPS(0-10) during the CPM-TASK. Melatonin alone or associated with amitriptyline was better than amitriptyline alone in improving pain on the VAS, whereas its association with amitriptyline produced only marginal additional clinical effects on FIQ and PPT. Trial registration Current controlled trail is registered at clinical upon under number NCT02041455. Registered January 16, 2014.
    BMC pharmacology & toxicology 07/2014; 15(1):40. DOI:10.1186/2050-6511-15-40
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    • "As an anxiolytic agent, MT has proven to be effective in preclinical studies as well as in humans (Caumo et al., 2009; Crupi et al., 2010; Papp et al., 2006; Srinivasan et al., 2006; Tian et al., 2010). Clinically, it has been successfully used to facilitate the discontinuation of benzodiazepine therapy in patients with insomnia (Garfinkel et al., 1999) and to reduce the anxiety scores in cataract surgery patients (Khezri and Merate, 2013). "
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    ABSTRACT: In spite the wide variety of drugs available for treating anxiety, this disorder continues to represent a worldwide health problem that is classified within the first 10 causes of disability. Therefore, the search continues for new antianxiety agents, particularly those not related to benzodiazepines. Even though melatonin has been prescribed as an anxiolytic drug, its use is currently limited due to its short half-life and photo-sensitivity, among other disadvantages. The present study explores the antianxiety properties of a new 1-N substituted melatonin analogue, M3C, in pinealectomized rats submitted to two behavioral tests (the cumulative burying behavior paradigm and the elevated plus-maze). Results from both tests show that M3C is effective as an anxiolytic-like agent, at doses lower than any other melatonin analogue previously reported. The blocking of these actions by luzindole together with the available data suggests that the anxiolytic properties of M3C are mediated by MT1 and MT2 receptors.
    Progress in Neuro-Psychopharmacology and Biological Psychiatry 06/2014; 51. DOI:10.1016/j.pnpbp.2014.01.015 · 3.69 Impact Factor
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    • "Although the efficacy of corticoids has been established in inflammatory chronic pain induced by arthritis, their chronic use has been shown to have several side effects, including circadian rhythm disruption (Nieman et al., 2010). Melatonin (MEL) may restore the circadian rhythm (Carpentieri et al., 2006; Slotten et al., 1999) and improve pain (Caumo, 2009; Esposito et al., 2010; Noseda et al., 2004; Shin et al., 2011; Tanuri et al., 2009). The antiinflammatory (Ambriz-Tututi et al., 2009) and antihyperalgesic effects of melatonin have been demonstrated both in animals (Laste et al., 2012) and in humans (Hussain et al., 2011). "
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    ABSTRACT: We assessed the therapeutic effect of exogenous melatonin (MEL), dexamethasone (DEXA), and a combination of both on nociceptive response induced by chronic inflammation and on the rest-activity circadian rhythm in rats. A total of 64 animals were randomly divided into eight groups of eight rats each: one control group and seven groups with complete Freund's adjuvant-inflamed animals (CFA; injection into the footpad). One of the CFA-inflamed groups did not receive any treatment; the other six were treated with melatonin (MEL), dexamethasone (DEXA), melatonin plus dexamethasone (MELDEXA), and their respective vehicles. Fifteen days after CFA injection, animals were treated with intraperitoneal injection of MEL (50 mg/kg) or its vehicle (8% ethanol in saline), DEXA (0.25 mg/kg) or its vehicle (saline), and MEL plus DEXA or their vehicles, for 8 days. The von Frey test was performed 24 h after the last administration of each treatment regimen. Hind paw thickness was measured using a pachymeter during the treatment days. The degree of swelling and histological findings were analyzed. All treated groups significantly reduced the severity of inflammation when compared with their vehicles (repeated-measures analysis of variance [ANOVA], p < 0.05 for all analyses). Inflamed animals treated with dexamethasone alone or associated with melatonin showed marked inhibition of histological findings. On the other hand, the group treated with melatonin remained with moderate inflammation. The CFA group showed a decrease in the mean rest-activity circadian rhythm, determined by the number of touch-detections per hour during water intake in comparison with the control group; only the group treated with melatonin showed a synchronized rest-activity rhythm. At the end of treatment, a significant increase was observed in hind paw withdrawal threshold on the von Frey test in the treated groups (one-way ANOVA, p < 0.05 for all). Our findings showed that melatonin (50 mg/kg) has strong chronobiotic and antinociceptive effects, but only mild anti-inflammatory effects. This evidence supports the hypothesis that melatonin can induce phase advance and circadian rhythm synchronization in rats with chronic inflammation.
    Chronobiology International 07/2013; 30(9). DOI:10.3109/07420528.2013.800088 · 3.34 Impact Factor
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