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The clinical management of inflammatory pain requires an optimal balance between effective analgesia and associated safety risks. To date, mechanisms associated with inflammatory pain are not completely understood because of their complex nature and the involvement of both peripheral and central mechanisms. This Expert Consensus document is intended to update clinicians about evolving areas of clinical practice and/or available treatment options for the management of patients with inflammatory pain.
Learn More >To address the need for long-term lasmiditan data, the GLADIATOR study evaluated the safety (primary) and efficacy (secondary) of lasmiditan for the intermittent, acute treatment of migraine attacks for up to 1 year.
Learn More >Gabapentinoid use has increased substantially in the past several years after initial promising data with regard to acute perioperative pain control. The purpose of this review is to critically appraise the evidence for the use of gabapentinoids for acute pain management and its impact on the development of chronic pain after surgery.
Learn More >Addiction neuroscience models posit that recurrent drug use increases reactivity to drug-related cues and blunts responsiveness to natural rewards, propelling a cycle of hedonic dysregulation that drives addictive behavior. Here, we assessed whether a cognitive intervention for addiction, Mindfulness-Oriented Recovery Enhancement (MORE), could restructure reward responsiveness from valuation of drug-related reward back to valuation of natural reward. Before and after 8 weeks of MORE or a support group control, prescription opioid users ( = 135) viewed opioid and natural reward cues while an electroencephalogram biomarker of target engagement was assessed. MORE was associated with decreased opioid cue-reactivity and enhanced capacity to regulate responses to opioid and natural reward cues. Increased positive affective responses to natural reward cues were associated with decreased craving and mediated MORE's therapeutic effects on opioid misuse. This series of randomized experiments provide the first neurophysiological evidence that an integrative behavioral treatment can remediate hedonic dysregulation among chronic opioid users.
Learn More >Vincristine, a widely used antineoplastic agent, is known to be neurotoxic and to lead to chemotherapy-induced peripheral neuropathy (CIPN), which is characterized by nerve damage. Growing evidence suggests that disruption of intracellular calcium homeostasis in peripheral neurons contributes largely to the pathological conditions of CIPN. Our previous study showed that forced expression of a peripheral nerve injury-induced small heat shock protein (Hsp), Hsp27, accelerates axon regeneration and functional recovery. In the current study, we examined whether neuronal expression of human Hsp27 (hHsp27) can prevent the inhibitory effects of vincristine in two mouse models of peripheral nerve injury, namely, sciatic nerve crush and CIPN.
Learn More >Recent research has suggested that the magnitudes of analgesic treatment effects estimated in clinical trials have decreased over time. Implications of these findings for future sample size calculations and clinical trial research designs have not been addressed. In this article, we examine the standardized effect size (SES) for average pain intensity (API) and worst pain intensity (WPI) outcomes from randomized clinical trials (RCTs) of analgesic treatments shown to be efficacious for chronic low back pain, fibromyalgia, osteoarthritis pain, painful diabetic peripheral neuropathy, and postherpetic neuralgia that were published between 1980 and 2016. API and WPI SESs have declined over time and are approximately 0.30 in the most recent trials. This is similar to the mean SESs found in recent RCTs of efficacious antidepressant medications for the treatment of depression. We propose that in many circumstances this value should be considered when conducting sample size determinations for phase 2 and 3 analgesic RCTs. Other methods to address the challenge of modest treatment effects by increasing trial efficiency and assay sensitivity are also briefly discussed. PERSPECTIVE: This article examines continuous pain intensity data obtained from analgesic treatment trials for chronic low back pain, fibromyalgia, osteoarthritis pain, painful diabetic peripheral neuropathy, and postherpetic neuralgia. Numerical declines in standardized effect sizes (SESs) were observed, with SESs being approximately 0.30 in the most recent trials.
Learn More >Mas-related G-protein-coupled receptor X1 (MRGPRX1) is a human sensory neuron-specific receptor and has been actively investigated as a therapeutic target for the treatment of pain. By use of two HTS screening hit compounds, 4-(4-(benzyloxy)-3-methoxybenzylamino)benzimidamide () and 4-(2-(butylsulfonamido)-4-methylphenoxy)benzimidamide (), as molecular templates, a series of human MRGPRX1 agonists were synthesized and evaluated for their agonist activity using HEK293 cells stably transfected with human MrgprX1. Conversion of the benzamidine moiety into a 1-aminoisoquinoline moiety carried out in the later stage of structural optimization led to the discovery of a highly potent MRGPRX1 agonist, -(2-(1-aminoisoquinolin-6-yloxy)-4-methylphenyl)-2-methoxybenzenesulfonamide (), not only devoid of positively charged amidinium group but also with superior selectivity over opioid receptors. In mice, compound displayed favorable distribution to the spinal cord, the presumed site of action for the MRGPRX1-mediated analgesic effects.
Learn More >Antibodies targeting calcitonin gene-related peptide (CGRP) or its receptor have shown efficacy in the prevention of migraine attacks. We investigated the efficacy and tolerability of fremanezumab, a fully humanised CGRP antibody, in patients with migraine who had previously not responded to two to four classes of migraine preventive medications.
Learn More >Intervertebral disc herniation is one of the common causes of low back pain. Adenosine monophosphate (AMP)-activated protein kinase (AMPK) activator drugs have been shown to reduce pain in several animal models. The present study examines if early treatment with the drug metformin, an indirect AMPK activator, and/or O304, a new direct AMPK activator, can reduce the mechanical hypersensitivity that develops after lumbar disc puncture in mice.
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