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Epigenetics is a process that alters gene activity or phenotype without any changes in the underlying DNA sequence or genotype. These biological changes may have deleterious effects and can lead to various human diseases. Ongoing research is continuing to illuminate the role of epigenetics in a variety of pathophysiologic processes. Several categories of epigenetic mechanisms have been studied including chromatin remodeling, DNA methylation, histone modification, and non-coding RNA mechanisms. These epigenetic changes can have a long-term effect on gene expression without any underlying changes in the DNA sequences. The underlying pathophysiology of disorders of brain-gut interaction and stress-induced visceral pain are not fully understood and the role of epigenetic mechanisms in these disorders are starting to be better understood. Current work is underway to determine how epigenetics plays a role in the neurobiology of patients with chronic visceral pain and heightened visceral nociception. More recently, both animal models and human studies have shown how epigenetic regulation modulates stress-induced visceral pain. While much more work is needed to fully delineate the mechanistic role of epigenetics in the neurobiology of chronic visceral nociception, the current study by Louwies et al., in Neurogastroenterology and Motility provides additional evidence supporting the involvement of epigenetic alterations in the central nucleus of the amygdala in stress-induced visceral hypersensitivity in rodents.
Learn More >The pathogenesis of chronic migraine remains unresolved. Recent studies have affirmed the contribution of GLUA1-containing AMPA receptors to chronic migraine. The dopamine D2 receptor, a member of G protein-coupled receptor superfamily, has been proven to have an analgesic effect on pathological headaches. The present work investigated the exact role of the dopamine D2 receptor in chronic migraine and its effect on GLUA1-containing AMPA receptor trafficking.
Learn More >A reciprocity between the stress and the pain system is recognized; however, the manner by which sex affects this reciprocity is unclear. Understanding the interactions of stress, pain, and sex may shed light on the apparent women's vulnerability to chronic pain, which often co-exists with increased distress, and to affective disorders, which often co-exist with chronic pain. The study's aim was to examine the effect of acute, validated, psychosocial stress on pain perception and modulation of women and men in a controlled manner. Participants were 82 women and 66 men. Heat-pain threshold, heat-pain tolerance and pain modulation by temporal summation of pain (TSP), and pain adaptation, were measured before and after exposure to the Montreal Imaging Stress Task (MIST) or to a sham task. The stress response was verified by perceived ratings of stress and anxiety, autonomic variables, and salivary cortisol. A significant stress response was obtained by the MIST among both sexes; however, women displayed a greater increase in perceived distress, and men displayed a greater increase in cortisol. Among women, TSP decreased and pain adaptation increased following the MIST, responses that were predicted by perceived distress levels. Among men, TSP increased following the MIST but was not predicted by the stress variables. In conclusion, acute stress manipulation seems to differentially affect both stress and pain responses of women and men: Women exhibited stress-induced antinociception, and men exhibited stress-induced pronociception. Higher perceived stress levels among women may trigger a temporary increase in pain inhibition mechanisms to serve evolutionary purposes.
Learn More >Despite a preponderance of pain-related attentional bias research, little is known about how these biases arise and change over time. We tested whether the degree of attentional bias malleability, that is, ability to acquire and relinquish patterns of selective attention towards pain information, predicts daily pain interference. Individuals with chronic pain (N = 66) completed a novel attentional bias malleability procedure based on a modified dot-probe paradigm. Participants received a contingency that encouraged an attentional preference toward and away from pain words across two counterbalanced blocks, and attentional bias was assessed before and after each contingency block. Participants then completed a daily diary for 7 days, including PROMIS-29 pain severity and interference. Multilevel modelling was conducted to predict daily pain interference from attentional bias malleability constructs, controlling for pain severity and demographic factors. Greater attentional bias (F1,391 = 3.97, p = .047), greater readiness to acquire an attentional bias (F1,389) = 4.92, p = .027), and less readiness to lose an acquired attentional bias toward pain (F1,354 = 5.18, p = .024) all predicted less pain interference. There was also an interaction between pain severity and overall attentional bias malleability (F1,62 = 5.48, p = .023), such that as pain severity increased, those who showed greater attentional bias malleability showed less corresponding increase in their pain interference, than those who showed less attentional bias malleability. This study adds new thinking to the dynamic nature of attentional bias, and how such biases might arise and influence pain outcomes.
Learn More >We described trends in pelvic pain characteristics over two years of follow-up among adolescents and adults with and without endometriosis participating in the longitudinal observational cohort of the Women's Health Study: From Adolescence to Adulthood (A2A), utilizing data reported at baseline and at years one and two of follow-up. Participants completed a questionnaire at baseline (between November 2012-May 2019) and annually thereafter that included validated measures of severity, frequency, and life interference of dysmenorrhea, acyclic pelvic pain, and dyspareunia. Our study population included 620 participants with surgically-confirmed endometriosis (rASRM stage I/II=95%) and 671 community and hospital-based controls; median age=19 and 24 years, respectively. The proportion reporting hormone use varied across the three years ranging from 88%-92% for cases and 56%-58% for controls. At baseline, endometriosis cases were more likely to report severe, frequent, and life interfering dysmenorrhea, acyclic pelvic pain, and dyspareunia compared to controls. Among cases, frequency and severity of dysmenorrhea and dyspareunia were relatively static across two years. However, acyclic pelvic pain improved. Severe acyclic pain decreased from 69% at baseline to 46% at Year 2. Daily pain decreased from 28% to 14%, and life interference from 68% to 38%. Trends among controls remained fairly stable across 2 years. Among endometriosis cases who completed the questionnaire at all three time points, 18% reported persistent, severe acyclic pelvic pain at all three time-points. Over time, different trends were observed by pelvic pain type among endometriosis cases and controls, supporting the importance of assessing multi-dimensional features of pelvic pain.
Learn More >Symptomatic Chiari 1 malformation (CM1) is a common condition in Neurosurgery. Surgery involves hindbrain decompression and restoration of CSF flow through different surgical approaches. No Class 1 evidence exists to suggest the superiority of any of the surgical techniques. To investigate current surgical practice for symptomatic CM1 patients in the United Kingdom (UK) and determine the willingness to participate in a randomised controlled trial (RCT) comparing different surgical techniques. An electronic survey was sent to consultant members of the Society of British Neurological Surgeons and the British Chiari-Syringomyelia Group. The questions covered pre-operative and intra-operative management, presence of equipoise/uncertainty in optimal technique and willingness to participate in an RCT. 98 responses were received. 67% operate on adults. 30% on adult and paediatric patients. There is variation in routine pre-operative use of: ICP monitoring (18%), flexion/extension x-rays (16%), venography (20%) and ophthalmology assessment (26%). 18% of neurosurgeons would not offer foramen magnum decompression when the presenting symptom is only refractory cough/sneeze headache. 15% routinely perform bony decompression alone in adults vs 8% in children. In 68% of adult cases, durotomy is performed routinely (46% of them leave the dura open, 54% perform a type of duroplasty) and 16% routinely resect the cerebellar tonsils. Only 17% leave the dura open in children. The most common indicators for durotomy are syringomyelia and intra-operative ultrasound findings. 61% believe there is equipoise/uncertainty in the optimal strategy for decompression and would be willing to participate in an RCT. Comments also mention the heterogeneity of CM1 and that treatment should be tailored to each patient. There is wide variation in pre- and intra-operative management of CM1 patients in the UK and the majority of neurosurgeons would be willing to participate in an RCT comparing bony decompression alone vs dural opening with/without duroplasty.
Learn More >Juvenile Idiopathic Arthritis (JIA) is a childhood-rheumatic disease with pain as a major early complaint, and in 10-17% pain remains a major symptom. Very few data exist on sensory threshold changes at the knee in JIA, a location in which inflammation often manifests. We determined whether JIA is associated with sensory threshold changes at the knee by using Quantitative Sensory Testing (QST) and established reference values at the knee of children.
Learn More >There is a clear link between skin disease and psychological factors and this relationship works both ways: skin diseases can cause psychological distress and psychological issues can worsen skin disease. There are a number of therapies that approach this problem from the psychological side and may be useful, especially as adjunctive therapies in select patients.
Learn More >A local anesthetic that provides analgesia lasting at least three days could significantly improve postoperative pain management. This study evaluated the analgesic efficacy and safety of an extended-release formulation of bupivacaine based on the injectable hydrogel carrier poly(N-isopropylacrylamide-co-dimethylbutyrolactone acrylamide-co-Jeffamine M-1000 acrylamide) (PNDJ).
Learn More >To review data for difelikefalin (Korsuva) intravenous solution for management of moderate-to-severe pruritus in hemodialysis (HD) patients.
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