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Many pain-triggering nociceptor neurons express TRPV1 or TRPA1, cation-selective channels with large pores that enable permeation of QX-314, a cationic analogue of lidocaine. Co-application of QX-314 with TRPV1 or TRPA1 activators can silence nociceptors. In this study, we describe BW-031, a novel more potent cationic sodium channel inhibitor, test whether its application alone can inhibit pain associated with tissue inflammation, and whether this strategy can also inhibit cough.
Learn More >Preclinical studies demonstrate that the NK1 receptor is involved in opioid reinforcement and withdrawal expression. Few studies have examined the impact of treatment with NK1 antagonists on opioid response in humans.
Learn More >Our aim was to describe the long-term prevalence, risk factors and impact on quality of life of Persistent Postsurgical Pain (PPP) following cardiac surgery.
Learn More >Ictal cutaneous allodynia, common in chronic migraine, is associated with reduced responses to acute treatment with triptans. Allodynia's impact on the efficacy of newer preventive treatments such as erenumab is unknown.
Learn More >Difelikefalin, a selective kappa opioid receptor agonist designed to limit central nervous system (CNS) penetration, is under development for the treatment of pruritus. Its hydrophilic, small-peptidic structure limits CNS entry, minimizing potential CNS-mediated adverse events (AEs). This study assessed the effect of difelikefalin on key relevant measures of respiratory depression in healthy volunteers. This single-center, randomized, double-blind, placebo-controlled, 3-way crossover study enrolled healthy, nonsmoking volunteers. Subjects were randomized to 1 of 3 treatment sequences of difelikefalin (1.0 or 5.0 mcg/kg intravenously [IV]) or placebo on sequential days with an intervening 24 (±2) hour washout period. The primary endpoints included incidence of increased end-tidal carbon dioxide (ETCO ) ≥10 mm Hg versus baseline or a level >50 mm Hg sustained ≥30 seconds, and incidence of reduction in saturation of peripheral oxygen (SpO ) to <92% sustained ≥30 seconds. Secondary endpoints included incidence of reduced respiratory rate and other safety assessments. Fifteen subjects were randomized and completed the study. No subject on placebo or difelikefalin met the increased ETCO or reduced SpO primary endpoint criteria for respiratory depression. All respiratory measures in each group remained near baseline values during 4-hour postdose observations. No subject met the reduced respiratory rate criterion or experienced clinically significant changes in ETCO , SpO , or respiratory rate. The most commonly reported treatment-emergent AEs (TEAEs; ≥20% of subjects) were paresthesia, hypoesthesia, and somnolence in the difelikefalin arms. All TEAEs were mild and resolved without intervention. Difelikefalin 1.0 and 5.0 mcg/kg IV did not produce respiratory depression.
Learn More >Migraine is one of the leading causes of years lived with disability and considered to be a major global health concern. Pharmacological preventive treatment often causes side effects that limit the adherence to longer-term treatment regiments. Both experimental and clinical evidence suggests that positive expectations can modulate pain and analgesic treatment effects. However, the role of expectations in migraine prophylactic treatment has not systematically been investigated. Here, we examined the influence of treatment expectation prior to commencing pharmacological preventive treatment on its efficacy and tolerability in N=134 episodic (30%) and chronic migraine (70%) patients in a prospective, longitudinal observational study over the course of six months. The migraine prophylaxis reduced the number of headache and migraine days with acceptable tolerability. Positive treatment expectation was associated with a generally lower number of headache and migraine days and a stronger reduction in headache days over the course of the treatment in chronic but not in episodic migraine patients. Moreover, patients with prior treatment showed a stronger reduction in headache days with higher expectation as compared to patients without prior experience. Our results underscore the relevance of further exploring the role of treatment expectation and its systematic modulation in migraine patients and other pain conditions.
Learn More >Fibromyalgia syndrome is one of the most common causes of chronic widespread pain, but pain accompanies a wide range of ancillary symptoms. To date, its aetiopathogenesis remains elusive, and diagnosis is exquisitely clinical, due to the lack of biomarkers or specific laboratory alterations in fibromyalgia patients. This position paper has the purpose to summarise the current scientific knowledge and expert opinions about the main controversies regarding fibromyalgia syndrome, namely: (i) fibromyalgia definition and why it is still not recognised in many countries as a distinct clinical entity; (ii) fibromyalgia severity and how to evaluate treatment outcome; (iii) how to treat fibromyalgia and which is a correct approach to fibromyalgia patients.
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