Accepted

The multinational phase 3b DELIVER trial was designed to evaluate the efficacy and safety of eptinezumab for migraine prevention in patients with prior preventive treatment failures across 17 countries. In the placebo-controlled portion, eptinezumab relative to placebo demonstrated greater reductions in migraine and headache frequency, migraine and headache severity, and acute medication use. The objective of this report is to describe the effects of eptinezumab on self-reported work productivity in the placebo-controlled portion of DELIVER.

The definitive pathogenic mechanisms underlying chronic migraine (CM) remain unclear. Mounting evidence from functional and structural magnetic resonance imaging (MRI) studies suggests that the caudate nucleus (CN) plays a role in the cognitive, sensory, and emotional integration of pain information in patients with migraine. However, evidence concerning the role played by CN in CM patients is limited. Here, we used the CN as the seed to explore patterns of functional connectivity (FC) among healthy controls (HCs), patients with episodic migraine (EM), and patients with CM.

Chronic pain patients often have anxiety disorders, and some of them suffer from anxiety even after analgesic administration. In this study, we investigated the role of AMPAR-mediated synaptic transmission in the ventromedial prefrontal cortex (vmPFC) in chronic pain-induced persistent anxiety in mice and explored potential drug targets. Chronic inflammatory pain was induced in mice by bilateral injection of complete Freund's adjuvant (CFA) into the planta of the hind paws; anxiety-like behaviours were assessed with behavioural tests; S-nitrosylation and AMPAR-mediated synaptic transmission were examined using biochemical assays and electrophysiological recordings, respectively. We found that CFA induced persistent upregulation of AMPAR membrane expression and function in the vmPFC of anxious mice but not in the vmPFC of non-anxious mice. The anxious mice exhibited higher S-nitrosylation of stargazin (an AMPAR-interacting protein) in the vmPFC. Inhibition of S-nitrosylation by bilaterally infusing an exogenous stargazin (C302S) mutant into the vmPFC rescued the surface expression of GluA1 and AMPAR-mediated synaptic transmission as well as the anxiety-like behaviours in CFA-injected mice, even after ibuprofen treatment. Moreover, administration of ZL006, a small molecular inhibitor disrupting the interaction of nNOS and PSD-95 (20 mg·kg·d, for 5 days, i.p.), significantly reduced nitric oxide production and S-nitrosylation of AMPAR-interacting proteins in the vmPFC, resulting in anxiolytic-like effects in anxious mice after ibuprofen treatment. We conclude that S-nitrosylation is necessary for AMPAR trafficking and function in the vmPFC under chronic inflammatory pain-induced persistent anxiety conditions, and nNOS-PSD-95 inhibitors could be potential anxiolytics specific for chronic inflammatory pain-induced persistent anxiety after analgesic treatment.

Primary headache disorders in particular migraine are one of the most common causes of disability worldwide. Given the high burden of migraine in terms of disability, there has been an effort to develop migraine specific therapies that has led to the availability of new drugs including 5HT receptor agonists-ditans (lasmiditan), small molecule calcitonin gene-related peptide (CGRP) receptor antagonists-gepants: (ubrogepant, rimegepant, atogepant) and anti-CGRP monoclonal antibodies (erenumab, fremanezumab, galcanezumab and eptinezumab). However, some of these treatments incur a high cost and may not be a feasible option for most patients in resource limited settings. Lasmiditan and the gepants are a good option for patients with moderate-severe migraine attacks who cannot use triptans due variously to poor tolerability, or cardio- or cerebrovascular disease. For practical purposes, the new anti-CGRP monoclonal antibodies are best reserved for patients who have failed to have efficacy or had intolerable side effects from multiple traditional oral preventives.

 Studies were carried out with the objective of evaluating the quality of life (QoL) of patients affected by chronic inflammatory demyelinating polyradiculopathy (CIDP). However, the cognitive issue is still little addressed.

Oxytocin (OXT) is a peptide hormone produced in the hypothalamus that plays a neuromodulatory role in emotion, stress, and anxiety. Due to its multidimensional role, OXT is a promising target for therapeutic interventions to treat pain.

Spinal cord stimulator (SCS) is approved to treat various pain conditions and is commonly seen in the chronic pain patient population. Due to the nature of the device and its location, infections associated with SCS have a particularly high morbidity. According to post-market data and medical device reports, 87% of patients receiving SCS implants were given perioperative antibiotics as the implantable neurostimulator or receiver pocket serve as the most common sites of infection. The most common antibiotics for surgical prophylaxis given are first-generation cephalosporins (cefalexin, cefazolin) at the time of implantation. If deep infection is suspected, imaging in the form of CT scan should be obtained as physical exam is not always sufficient. For infections involving the epidural space, vertebra, or intervertebral discs, MRI is the preferred imaging modality. If meningitis is suspected, a lumbar puncture is recommended. Positive cultures can help guide antibiotic therapy.

Chronic pain has a large individual and societal burden. Previous reviews have shown that internet-based cognitive-behavioral therapy (iCBT) can support patients' pain coping. However, factors related to participant experience of iCBT and effective and safe iCBT delivery for chronic pain have not recently been summarized.

To explore how patients in biopsychosocial pain rehabilitation perceive encounters with interprofessional teams. The focus of this article is to explore how interactions can perpetuate or diminish chronic pain stigma.

Oxycodone is a commonly used oral opioid in children for treating postoperative pain. Highly polymorphic gene metabolizes oxycodone into its more potent metabolite, oxymorphone. We hypothesized that altered activity due to polymorphisms will influence oxycodone requirements {relative oxycodone use [oxycodone morphine equivalents (MEq)/total MEq] to maintain analgesia} (primary outcome) and risk for oxycodone induced side-effects such as respiratory depression (RD) and emesis (secondary outcomes). We also explored the influence of genotype availability and provider guidance on oral opioid prescription patterns.