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Multimorbidity refers to the presence of two or more chronic health conditions within one person, where no one condition is primary. Research suggests that multimorbidity is highly correlated with chronic pain, which is pain lasting longer than 3 months. Psychotherapeutic interventions for people living with chronic illness have resulted in reduced symptom reporting and improved psychological well-being. There is a dearth of research, however, using online psychotherapy for people living with multimorbidity where chronic pain is a central condition. This study will compare the effectiveness of an online acceptance and commitment therapy (ACT) intervention with a waiting list control condition in terms of improving health-related quality of life (HRQoL) and reducing levels of pain interference in people with chronic pain and at least one other condition.
Learn More >An adequate response of a living cell to the ever-changing environment requires integration of numerous sensory inputs. In many cases, it can be achieved even at the level of a single receptor molecule. Polymodal transient receptor potential (TRP) channels have been shown to integrate mechanical, chemical, electric, and thermal stimuli. Inappropriate gating can lead to pathologies. Among the >60 known TRP vanilloid subfamily (V) 4 mutations that interfere with bone development are Y602C or R616Q at the S4-S5 linker. A cation-π bond between the conservative residues Y602 and R616 of neighboring subunits appears likely in many homologous channel structures in a closed state. Our experiments with TRPV4 mutants indicate that the resting-closed state remains stable while the bond is substituted by a salt bridge or disulfide bond, whereas disruption of the contact by mutations like Y602C or R616Q produces gain-of-function phenotypes when TRPV4 is heterologously expressed in the oocyte or yeast. Our data indicate that the Y602-R616 cation-π interactions link the four S4-S5 linker helices together, forming a girdle backing the closed gate. Analogous cation-π bonds and the girdle are seen in many closed TRP channel structures. This girdle is not observed in the cryo-EM structure of amphibian TRPV4 (Protein Data Bank ID code 6BBJ), which appears to be in a different impermeable state-we hypothesize this is the inactivated state.
Learn More >To determine the effect of erenumab, a human monoclonal antibody targeting the calcitonin gene-related peptide receptor, on health-related quality of life (HRQoL), headache impact, and disability in patients with chronic migraine (CM).
Learn More >Knee osteoarthritis (OA) is among the most common and disabling persistent pain conditions, with increasing prevalence in the developed world, and affects women to a greater degree than men. In the USA, the growth of knee OA has been paralleled by an increase in rates of total knee arthroplasty (TKA), a surgical treatment option for late-stage knee OA. While TKA outcomes are generally good, postoperative trajectories of pain vary widely, with some patients reporting a complete absence of pain, but with a significant minority reporting worsening pain. Biopsychosocial factors, including anxiety and depression, are known to contribute importantly to the experience of joint pain, with women reporting a higher degree of negative affective symptoms.
Learn More >Genetics studies on the placebo hypoalgesic effect highlight a promising link between single nucleotide polymorphisms (SNPs) in the dopamine, opioid, and endocannabinoid genes and placebo hypoalgesia. However, epistasis and replication studies are missing. In this study, we expanded upon previous findings related to the three SNPs in the opioid receptor mu subunit (OPRM1 rs1799971), catechol-O-methyltransferase (COMT rs4680), and fatty acid amide hydrolase (FAAH rs324420) genes associated with placebo hypoalgesia and tested the effect of a three-way interaction on placebo hypoalgesia. Using two well-established placebo procedures (verbal suggestion, learning paradigm), we induced significant placebo hypoalgesic effects in 160 healthy participants. We found that individuals with OPRM1 AA combined with FAAH Pro/Pro and those carrying COMT met/met together with FAAH Pro/Pro showed significant placebo effects. Participants with COMT met/val alleles showed significant placebo effects independently of OPRM1 and FAAH allele combinations. Finally, the model that included the placebo procedure and genotypes predicted placebo responsiveness with a higher accuracy (area under the curve, AUC=0.773) as compared to the SNPs alone indicating that genetic variants can only partially explain the placebo responder status. Our results suggest that the endogenous mu-opioid system with a larger activation in response to pain in the met/val allele carriers as well as the synergism between endogenous mu-opioid system and cannabinoids might play the most relevant role in driving hypoalgesic responses. Future epistasis studies with larger sample sizes will help us to fully understand the complexity of placebo effects and explain the mechanisms that underlie placebo responsiveness.
Learn More >Low back pain (LBP) is a public health concern because it is highly prevalent and the leading cause of disability worldwide. Psychologically informed physical therapy (PIPT) is a secondary prevention approach that first aims to identify individuals at high risk for transitioning to chronicity and then provides tailored treatment to reduce that risk. Training models that are feasible to implement with acceptable training quality are needed to improve scalability for widespread implementation of PIPT. This manuscript describes the PIPT training program that was developed for training physical therapists providing PIPT in the TARGET trial.
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