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Cold allodynia is often seen in the acute phase of oxaliplatin treatment, but the underlying pathophysiology remains unclear.
Learn More >This proof-of-concept study demonstrates and validates a novel approach that automatically translates information derived from patient reported outcome measures (PROMs) into a standardized functioning report based on the International Classification of Functioning, Disability and Health (ICF).
Learn More >The kappa opioid receptor (κOR) is an important target for pain therapeutics to reduce depression and other harmful side effects of existing medications. The analgesic activity is mediated by κOR signaling through the adenylyl cyclase-inhibitory family of Gi protein. Here, we report the three-dimensional (3D) structure for the active state of human κOR complexed with both heterotrimeric Gi protein and MP1104 agonist. This structure resulted from long molecular dynamics (MD) and metadynamics (metaMD) simulations starting from the 3.1-Å X-ray structure of κOR-MP1104 after replacing the nanobody with the activated Gi protein and from the 3.5-Å cryo-EM structure of μOR-Gi complex after replacing the 168 missing residues. Using MD and metaMD we discovered interactions to the Gi protein with strong anchors to two intracellular loops and transmembrane helix 6 of the κOR. These anchors strengthen the binding, contributing to a contraction in the binding pocket but an expansion in the cytoplasmic region of κOR to accommodate G protein. These remarkable changes in κOR structure reveal that the anchors are essential for activation.
Learn More >Sleep and opioid medications used to treat insomnia and chronic pain are associated with adverse side effects (falls and cognitive disturbance). Although behavioural treatments such as cognitive behavioral therapy for insomnia (CBT-I) and pain (CBT-P) improve sleep and clinical pain, their effects on sleep and opioid medication use are unclear. In this secondary analysis of published trial data, we investigated whether CBT-I and CBT-P reduced reliance on sleep/opioid medication in patients with fibromyalgia and insomnia (FMI). Patients with FMI (n = 113, M = 53.0, SD = 10.9) completed 8 weeks of CBT-I (n = 39), CBT-P (n = 37) or waitlist control (WLC; n = 37). Participants completed 14 daily diaries at baseline, post-treatment and 6-month follow-up, assessing sleep and opioid medication usage. Multilevel modelling examined group by time effects on days of medication use. A significant interaction revealed CBT-P reduced the number of days of sleep medication use at post-treatment, but usage returned to baseline levels at follow-up. There were no other significant within- or between-group effects. CBT-P led to immediate reductions in sleep medication usage, despite lack of explicit content regarding sleep medication. CBT-I and CBT-P may be ineffective as stand-alone treatments for altering opioid use in FMI. Future work should explore CBT as an adjunct to other behavioural techniques for opioid reduction.
Learn More >Migraine has many presumed comorbidities which have rarely been compared between samples with and without migraine. Examining the association between headache pain intensity and monthly headache day (MHD) frequency with migraine comorbidities is novel and adds to our understanding of migraine comorbidity.
Learn More >Opioid prescriptions for treatment of pain in emergency departments (EDs) are associated with long-term opioid use. The temporal pattern of opioid prescribing in the context of the opioid epidemic remains unknown.
Learn More >In response to the national opioid public health crisis, there is an urgent need to develop nonopioid solutions for effective pain management. Neurosteroids are endogenous molecules with pleotropic actions that show promise for safe and effective treatment of chronic low back pain.
Learn More >Family members are cited as a common source of prescription opioids used for nonmedical reasons. However, the overdose risk associated with exposure to opioids prescribed to family members among adolescents and young adults is not well established.
Learn More >Pruritus (itch) is a cardinal symptom in atopic dermatitis (AD).
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