montelukast and Pain

Cysteinyl leukotrienes (CysLTs) are lipid mediators of inflammation. In patients with sickle cell disease (SCD), levels of CysLTs are increased compared with controls and associated with a higher rate of hospitalization for pain. We tested the hypothesis that administration of the CysLT receptor antagonist montelukast would improve SCD-related comorbidities, including pain, in adolescents and adults with SCD. In a phase 2 randomized trial, we administered montelukast or placebo for 8 weeks. The primary outcome measure was a >30% reduction in soluble vascular cell adhesion molecule 1 (sVCAM), a marker of vascular injury. Secondary outcome measures were reduction in daily pain, improvement in pulmonary function, and improvement in microvascular blood flow, as measured by laser Doppler velocimetry. Forty-two participants with SCD were randomized to receive montelukast or placebo for 8 weeks. We found no difference between the montelukast and placebo groups with regard to the levels of sVCAM, reported pain, pulmonary function, or microvascular blood flow. Although montelukast is an effective treatment for asthma, we did not find benefit for SCD-related outcomes. This clinical trial was registered at www.clinicaltrials.gov as #NCT01960413.

Topics: Acetates; Adolescent; Adult; Anemia, Sickle Cell; Cyclopropanes; Humans; Leukotriene Antagonists; Pain; Quinolines; Sulfides

Recurrent aphthous stomatitis (RAS) is characterized by recurrent painful oral ulcers whose etiology remains largely unknown. Numerous therapeutic protocols have been tried so far, but effectiveness remains an issue.. To test a new drug for patients with recurrent oral aphthae nonresponsive to local corticosteroid therapy, we compared the therapeutic effectiveness and adverse effects of systemic prednisone and systemic montelukast in a placebo-controlled trial.. Sixty patients suffering from minor RAS for > or =6 months were studied and randomly assigned to 3 groups of 20 each in a double-blind study. Patients of group A took 25 mg prednisone orally daily for 15 days, 12.5 mg daily for 15 days, 6.25 mg daily for 15 days, then 6.25 mg on alternate days for 15 days. Patients of group B took 10 mg montelukast orally every evening and then on alternate days for the second month. Patients of group C took 100 mg cellulose (placebo) by mouth daily for the first month and on alternate days for the second month. Outcomes assessed were days til pain cessation, days to ulcer healing, and number of aphthae occurring during the follow-up period.. Both prednisone and montelukast were effective in reducing the number of lesions and improving pain relief and ulcer healing when compared with placebo. Prednisone was more effective than montelukast in pain cessation (P < .0001) and in accelerating ulcer healing (P < .0001). However, adverse drug reactions recorded during the entire trial were more common in the prednisone group compared with montelukast (10%) and placebo (10%).. These data suggest that the effectiveness of systemic montelukast is similar to that of systemic prednisone in patients with RAS. The lack of serious side effects makes montelukast a candidate drug to use in cases of RAS where pharmacologic therapy for long periods is needed.

Topics: Acetates; Adolescent; Adult; Cyclopropanes; Double-Blind Method; Female; Glucocorticoids; Humans; Leukotriene Antagonists; Male; Middle Aged; Pain; Pilot Projects; Prednisolone; Quinolines; Stomatitis, Aphthous; Sulfides; Treatment Outcome

Montelukast, a competitive cysteinyl leucotriene-1 receptor antagonist, reduces airway eosinophilia in asthmatics. We evaluated the effect of this drug in children with eosinophilic duodenitis, defined histologically as duodenal mucosa with peak eosinophil count of more than 10 eosinophils/hpf.. Forty children and adolescents (6-18 yr) with dyspepsia and duodenal eosinophilia were enrolled in a double blind, randomized, placebo-controlled, cross-over study of monteleukast therapy. Subjects were randomized to receive either 10 mg montelukast or an identical placebo once daily and were evaluated on day 14 for symptomatic and biochemical responses. Subjects were also randomized to one of two blood sampling schemes to evaluate montelukast pharmacokinetics.. Using a post treatment global pain assessment, a positive clinical response was observed in 62.1% of patients receiving montelukast compared with 32.4% on placebo (p < 0.02). Pain assessment score deteriorated in 45% of montelukast responders (5/11) after cross-over to placebo and improved in 62% (8/13) of placebo non-responders on cross-over to montelukast. In patients with peak duodenal eosinophil counts between 20-29/hpf (n=19), a positive pain assessment response was observed in 84% of patients receiving montelukast compared to 42% receiving placebo (p < 0.01). Response rate did not differ by age, gender or histologic findings at baseline. Pharmacokinetic analysis yielded parameter estimates for absorption rate constant (Ka), apparent volume of distribution (Vd/F) and elimination rate constant (Kel) of 0.42 h, 0.19 L/kg and 0.26 h, respectively. The relative extent of systemic drug exposure was comparable to that observed in previous pediatric investigations with similar weight-adjusted montelukast doses. Neither dose nor calculated drug exposure were associated with the level of post treatment pain assessment or the change in biochemical markers.. These data suggest a beneficial role for montelukast in the treatment of pediatric patients with dyspepsia associated with duodenal eosinophilia.

Topics: Acetates; Adolescent; Child; Cross-Over Studies; Cyclopropanes; Double-Blind Method; Duodenal Diseases; Dyspepsia; Eosinophilia; Female; Humans; Intestinal Mucosa; Leukotriene Antagonists; Male; Pain; Quinolines; Sulfides; Treatment Outcome

This study aimed to investigate the involvement of opioid receptors in the systemic and peripheral antinociceptive activities of montelukast in different animal models of pain. Rats and mice were injected with montelukast to produce analgesia. The formalin and acetic acid-induced writhing tests were used to assess the nociceptive activity. The results showed that i.p. administration of montelukast (0.3-10mg/kg) dose-dependently reduced flinching behavior in both the first and second phases of formalin test with mean ED50 of 0.55 and 5.31mg/kg, respectively. Also, intraplantar administration of montelukast (3-30μg/paw) produced antinociception against the two phases of formalin assay in a dose-dependent way with mean ED30 of 2.92 and 8.11μg/paw, respectively. Furthermore, pre-treatment with naloxone (a non-selective opioid receptor antagonist) significantly inhibited both the systemic and also peripheral antinociceptive actions of montelukast in formalin test. In writhing test, the results showed that intraperitoneal administration of montelukast (3-10mg/kg) significantly reduced the writhe number induced by acetic acid in mice. Moreover, co-administration of non-effective doses of montelukast (0.3 and 1mg/kg; i.p.) and morphine (0.25mg/kg; i.p.) significantly decreased the writhes number induced by acetic acid. Also, this effect was naloxone-reversible. These findings suggest that the systemic and peripheral antinociception produced by montelukast were mediated through the opioid receptors in central and peripheral nervous systems. Moreover, combination of montelukast and morphine could be noted as a new strategy for pain relief.

Topics: Acetates; Acetic Acid; Analgesics; Animals; Behavior, Animal; Cyclopropanes; Disease Models, Animal; Drug Synergism; Formaldehyde; Male; Mice; Naloxone; Pain; Quinolines; Rats; Receptors, Opioid; Sulfides; Visceral Pain

Baseline level of the cysteinyl leukotriene (CysLT), leukotriene E4 (LTE4), is associated with an increased pain rate in children and adults with sickle cell disease (SCD). To provide additional evidence for a role of CysLTs in the pathogenesis of vaso-occlusion, we tested the hypothesis that LTE4 levels will increase within an individual during painful episodes compared to baseline. In a cohort of 19 children and adults with SCD, median LTE4 levels increased from 82.36 pg/mg creatinine at baseline to 162.81 pg/mg creatinine during a painful episode (P < 0.001). These data further support a contribution of CysLTs to the process of vaso-occlusion.

Topics: Acetates; Adolescent; Adult; Anemia, Sickle Cell; Anti-Asthmatic Agents; Asthma; beta-Thalassemia; Biomarkers; Child; Cohort Studies; Cyclopropanes; Female; Fetal Hemoglobin; Hemoglobin C Disease; Heterozygote; Hospitalization; Humans; Ischemia; Leukotriene Antagonists; Leukotriene E4; Male; Pain; Quinolines; Retrospective Studies; Sickle Cell Trait; Sulfides; Young Adult

Pain is commonly associated with inflammation. Several mediators including prostaglandins have been implicated in pain and inflammation. However, the recent reports indicated the role of leukotrienes as signaling molecules in pain. The present study was aimed to evaluate the effect of 5-LOX inhibitor, zileuton in nociceptive paradigms including inflammatory pain. Acetic acid-induced writhing, tail flick and hot plate tests to assess pain response were used. The effect on carrageenan-induced mechanical hyperalgesia, and acetic acid-induced vascular permeability was also determined. Zileuton (ED50=31.81 mg/kg p.o.), zafirlukast (ED50=6.19 mg/kg p.o.), montelukast (ED50=7.17 mg/kg p.o.) inhibited acetic acid-induced writhing in mice. Further, zileuton and ZK 158252, leukotriene B4 receptor antagonist did not alter basal response against tail flick and hot plate assays. Acetic acid-induced vascular permeability was significantly inhibited by zileuton. Oral administration of zileuton showed efficacy against carrageenan-induced mechanical hyperalgesia and also reversed histological changes in paw biopsies. These data suggest that zileuton, a 5-LOX inhibitor, exhibited antinociceptive effect in paradigms of inflammatory pain.

Topics: Acetates; Acetic Acid; Analgesics; Animals; Capillary Permeability; Carrageenan; Cyclopropanes; Dose-Response Relationship, Drug; Female; Hindlimb; Hydroxyurea; Hyperalgesia; Indoles; Inflammation; Leukotriene Antagonists; Lipoxygenase Inhibitors; Male; Mice; Pain; Pain Measurement; Phenylcarbamates; Quinolines; Rats; Rats, Wistar; Receptors, Leukotriene B4; Sulfides; Sulfonamides; Tosyl Compounds

Churg-Strauss syndrome (CSS) is a disseminated small vessel vasculitis characterized by late-onset asthma, upper airways disease, eosinophilia and late neurological manifestations such as peripheral neuropathy. Recently, several cases of CSS have been reported in patients treated with leukotriene antagonists after weaning corticosteroids. We describe a case of CSS developed while the patient was receiving montelukast for asthma treatment, after corticosteroids withdrawal. A causal relationship between montelukast therapy and CSS is hypothesized.

Topics: Acetates; Aged; Asthma; Churg-Strauss Syndrome; Cyclopropanes; Electrophysiology; Female; Humans; Leukotriene Antagonists; Pain; Peripheral Nervous System Diseases; Quinolines; Sulfides

Topics: Acetates; Cyclopropanes; Cystitis, Interstitial; Female; Humans; Leukotriene Antagonists; Pain; Pilot Projects; Quinolines; Sulfides; Urination Disorders