Browse by Audience
The voltage-gated sodium channel Na1.2 is responsible for the initiation and propagation of action potentials in the central nervous system. We report the cryo-electron microscopy structure of human Na1.2 bound to a peptidic pore blocker, the μ-conotoxin KIIIA, in the presence of an auxiliary subunit β2 to an overall resolution of 3.0 Å. The immunoglobulin (Ig) domain of β2 interacts with the shoulder of the pore domain through a disulfide bond. The 16-residue KIIIA interacts with the extracellular segments in repeats I to III, placing Lys7 at the entrance to the selectivity filter. Many interacting residues are specific to Na1.2, revealing a molecular basis for KIIIA specificity. The structure establishes a framework for rational design of subtype-specific blockers for Na channels.
Learn More >Medication-overuse headache (MOH) is a common chronic headache caused by overuse of headache analgesics. It has similarities with substance dependence disorders. The treatment of choice for MOH is withdrawal of the offending analgesics. Behavioral brief intervention treatment using methods adapted from substance misuse settings is effective. Here we investigate the severity of analgesics dependence in MOH using the Severity of Dependence Scale (SDS), validate the SDS score against formal substance dependence diagnosis based on the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) and examine whether the SDS predicts successful withdrawal.
Learn More >Features suggestive of neuropathic pain (NP) have been described in RA in addition to nociceptive pain. We aimed to determine the clinical predictors of NP in RA patients and study its association with radiographic structural damage.
Learn More >When investigating the role of facilitatory and inhibitory pain mechanisms such as conditioned pain modulation (CPM) and temporal summation of pain (TSP), it is important to take both into consideration in a single experimental model to provide the most information on subgroups of patients. Therefore, the objective of this study was to identify subgroups in a large population of pediatric patients with chronic pain based on their facilitatory and inhibitory pain mechanisms and compare them with control subjects.
Learn More >Learned helplessness develops with prolonged exposure to uncontrollable stressors and is therefore germane to individuals living with pain or other poorly controlled chronic diseases. This study has developed a helplessness scale for chronic conditions distinct from previous scales that blur the conceptualization of control constructs. Extant measures commonly examine controllability, not the three pillars of helplessness identified by Maier and Seligman (1976): cognitive, emotional, and motivational/motor deficits.
Learn More >Acupuncture is a complementary and nonpharmacological intervention that can be effective for the management of chronic pain in addition to or instead of medication. Various animal models for neuropathic pain, inflammatory pain, cancer-related pain, and visceral pain already exist in acupuncture research. We used a newly validated human pain model and examined whether acupuncture can influence experimentally induced dental pain. For this study, we compared the impact of manual acupuncture (real acupuncture), manual stimulation of a needle inserted at non-acupuncture points (sham acupuncture) and no acupuncture on experimentally induced dental pain in thirty-five healthy men who were randomized to different sequences of all three interventions in a within-subject design. BORG CR10 pain ratings and autonomic responses (electrodermal activity and heart rate variability) were investigated. An initial mixed model with repeated measures included preintervention pain ratings and the trial sequence as covariates. The results showed that acupuncture was effective in reducing pain intensity when compared to no acupuncture (β =-0.708, p = 0.002), corresponding to a medium Cohen's d effect size of 0.56. The comparison to the sham acupuncture revealed no statistically significant difference. No differences in autonomic responses between real and sham acupuncture were found during the intervention procedures. Perspective: This study established a dental pain model for acupuncture research and provided evidence that experimentally induced dental pain can be influenced by either real acupuncture or manual stimulation of needles at non-acupuncture points. The data do not support that acupoint specificity is a significant factor in reducing experimental pain. Trial registration: The study was registered at clinicaltrials.gov (registration ID: NCT02589418).
Learn More >This longitudinal case-control study aims to 1) compare symptoms and functioning in otherwise healthy adolescents with versus without a parent with chronic pain (Parent CP+/Parent CP-) 2) test adolescent sex as a moderator of the relation between parent CP group and child functioning, and 3) determine changes in adolescent pain over one year. Adolescents (n=140; ages 11-15) completed tests of pain responsivity and physical function, as well as self-report measures assessing pain characteristics, somatic symptoms, and physical and psychosocial functioning. Self-reported pain and somatic symptoms were re-assessed one year later. Adolescents in the Parent CP+ group reported greater pain, somatic symptoms, and worse physical health than Parent CP- youth. Parent CP+ youth performed worse on all tests of physical function. Some observed effects were stronger for girls than boys. There were no differences between groups on pain responsivity. Both groups reported increased pain and somatic symptoms from baseline to one-year follow-up, with the Parent CP+ group reporting the highest level of symptoms at both time points. This study highlights the potential impact of parental pain status on children, particularly daughters, and is the first to document objective physical functioning differences in youth at risk for developing chronic pain. Perspective: Adolescents who have a parent with chronic pain demonstrate higher pain and lower physical function than adolescents who have a parent without chronic pain. Group differences in pain and somatic symptoms persist over one year. Family based interventions are needed for comprehensive pain prevention and treatment.
Learn More >The brainstem has been discussed as the main player in the pathogenesis of migraine. Dysfunctional brainstem nuclei and their abnormal connections to other key brain centers may contribute to headache and other symptoms of migraine. In the present study, 32 patients with migraine without aura (MWoA) and 32 age- and sex-matched healthy controls (HCs) underwent resting-state fMRI scans. We used masked independent analysis (mICA) to investigate whether patients with MWoA exhibited abnormal brainstem nuclei-cortical functional connectivity (FC). The mICA can suppress adjacent physiological noise and prevent results from being driven by the much stronger signals of the surrounding structures. Regional homogeneity (ReHo) was used to investigate whether the brainstem regions with abnormal FC to other brain areas exhibited abnormal regional neuronal activity. Patients with MWoA showed significantly weaker FC between the posterior pons and the left superior parietal lobule, the left middle temporal gyrus and the left middle frontal gyrus. Furthermore, patients with MWoA exhibited significantly decreased ReHo values in the posterior pons compared with HCs, and the posterior pons ReHo value was significantly negatively correlated with HIT-6 scores in the MWoA group. Patients with MWoA exhibited functional abnormalities in the posterior pons and weakened connections between the posterior pons and several key cortical brain areas involved in pain processing during the resting state. Perspective: This study provided increased evidence that the pons is involved in pathophysiological mechanism of migraine, and weakened connections suggest that the touch and pain sensation of migraine sufferers may not be properly relayed to cortical processing areas, which may be associated with the pathogenesis of MWoA.
Learn More >