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Map the current literature investigating autonomy development, identity development, and peer relationships in young people aged 10-24 years with chronic pain.
Learn More >Osteoarthritis (OA) manifests with chronic pain, motor impairment, and proprioceptive changes. However, the role of the brain in the disease is largely unknown. Here, we studied brain networks using the mathematical properties of graphs in a large sample of knee and hip OA (KOA, n = 91; HOA, n = 23) patients. We used a robust validation strategy by subdividing the KOA data into discovery and testing groups and tested the generalizability of our findings in HOA. Despite brain global topological properties being conserved in OA, we show there is a network wide pattern of reorganization that can be captured at the subject-level by a single measure, the hub disruption index. We localized reorganization patterns and uncovered a shift in the hierarchy of network hubs in OA: primary sensory and motor regions and parahippocampal gyrus behave as hubs and insular cortex loses its central placement. At an intermediate level of network structure, frontoparietal and cingulo-opercular modules showed preferential reorganization. We examined the association between network properties and clinical correlates: global disruption indices and isolated degree properties did not reflect clinical parameters; however, by modeling whole brain nodal degree properties, we identified a distributed set of regions that reliably predicted pain intensity in KOA and generalized to hip OA. Together, our findings reveal that while conserving global topological properties, brain network architecture reorganizes in OA, at both global and local scale. Network connectivity related to OA pain intensity is dissociated from the major hub disruptions, challenging the extent of dependence of OA pain on nociceptive signaling.
Learn More >Post-traumatic headache due to mild traumatic brain injury: Current knowledge and future directions.
Post-traumatic headache is one of the most common and persistent symptoms following mild traumatic brain injury. The objective of this narrative review is to provide an update on the diagnostic criteria, clinical presentation, epidemiology, pathophysiology, and treatment of post-traumatic headache, and to identify future research priorities.
Learn More >Microglia play an important role in the central sensitization and chronic pain. However, a direct connection between microglial function and pain development in vivo remains incompletely understood. To address this issue, we applied chemogenetic approach by using CXCR1:R26 transgenic mice to enable expression of inhibitory Designer Receptors Exclusively Activated by Designer Drugs (Gi DREADD) in microglia. We found that microglial Gi DREADD activation inhibited spinal nerve transection (SNT)-induced microglial reactivity as well as chronic pain in both male and female mice. Gi DREADD activation downregulated the transcription factor interferon regulatory factor 8 (IRF8) and its downstream target pro-inflammatory cytokine interleukin 1 beta (IL-1β). Using in vivo spinal cord recording, we found that activation of microglial Gi DREADD attenuated synaptic transmission following SNT. Our results demonstrate that microglial Gi DREADD reduces neuroinflammation, synaptic function and neuropathic pain after SNT. Thus, chemogenetic approaches provide a potential opportunity for interrogating microglial function and neuropathic pain treatment.
Learn More >Alcohol Use Disorder (AUD) is a chronic relapsing disorder characterized by compulsive alcohol intake, loss of control over alcohol intake, and a negative emotional state when access to alcohol is prevented. AUD is also closely tied to pain, as repeated alcohol drinking leads to increased pain sensitivity during withdrawal. The sigma-2 receptor, recently identified as transmembrane protein 97 (σ2R/TMEM97), is an integral membrane protein involved in cholesterol homeostasis and lipid metabolism. Selective σ2R/Tmem97 modulators have been recently shown to relieve mechanical hypersensitivity in animal models of neuropathic pain as well as to attenuate alcohol withdrawal signs in C. elegans and to reduce alcohol drinking in rats, suggesting a potential key role for this protein in alcohol-related behaviors. In this study, we tested the effects of a potent and selective σ2R/TMEM97 ligand, JVW-1034, on heavy alcohol drinking and alcohol-induced heightened pain states in mice using an intermittent access model. Administration of JVW-1034 decreased both ethanol intake and preference for ethanol, without affecting water intake, total fluid intake, or food intake. Notably, this effect was specific for alcohol, as JVW-1034 had no effect on sucrose intake. Furthermore, JVW-1034 reduced both thermal hyperalgesia and mechanical hypersensitivity in ethanol withdrawn mice. Our data provide important evidence that modulation of σ2R/TMEM97 with small molecules can mediate heavy alcohol drinking as well as chronic alcohol-induced heightened pain sensitivity, thereby identifying a promising novel pharmacological target for AUD and associated pain states.
Learn More >Persistent post-traumatic headache (PTH) is a common sequela of mild traumatic brain injury (TBI) and retrospective assessments have found a migraine-like phenotype to be very frequent. This has raised a discussion of shared underlying mechanisms and whether persistent PTH is simply trauma-triggered migraine.
Learn More >The striking difference between men and women in headache prevalence is suggested to develop in adolescence. Although headaches are common and affect quality of life and daily functioning, the evidence needed to develop effective counselling and preventive approaches is still limited.Using data collected at age 11, 14, 17 and 20 years in the Dutch PIAMA birth cohort study (n=3064 with > 1 questionnaire), we assessed headache prevalence and incidence in girls and boys and explored associations with early life, environmental, lifestyle, health and psychosocial factors. Associations were analysed longitudinally with generalized linear mixed models and discrete time hazard models.From age 11 to 20, the prevalence of headache increased from 9.4% to 19.8% in girls and hardly changed in boys (7.6% to 6.1%). Headache commonly co-occurred with other unfavorable health and psychosocial conditions. 88% of the girls and 76% of boys with headache also reported at least one of the following at age 17: sleeping problems, asthma, hay fever, musculoskeletal complaints, fatigue, low mental health or worrying. Results suggest higher headache prevalence in adolescents following lower educational tracks, in those who skip breakfast >2 days per week and in boys exposed to tobacco smoke in infancy. In girls, sleeping problems and musculoskeletal complaints were associated with higher odds of incident headache and residential greenness with lower odds of incident headache.The high prevalence and strong female predominance of headache, already in adolescence and often with comorbidities deserve recognition by professionals in (preventive) health care settings and schools.
Learn More >In the present study, we demonstrated that there is a direct relationship between scratching behaviors induced by itch and functional changes in the brain reward system. Using a conditional place preference test, the rewarding effect was clearly evoked by scratching under both acute and chronic itch stimuli. The induction of ΔFosB, a member of the Fos family of transcription factors, was observed in dopamine transporter (DAT)-positive dopamine neurons in the ventral tegmental area (VTA) of mice suffering from a chronic itch sensation. Based on a cellular analysis of scratching-activated neurons, these neurons highly expressed tyrosine hydroxylase (TH) and DAT genes in the VTA. Furthermore, in an in vivo microdialysis study, the levels of extracellular dopamine in the nucleus accumbens (NAcc) were significantly increased by transient scratching behaviors. To specifically suppress the mesolimbic dopaminergic pathway using pharmacogenetics, we used the TH-cre/hM4Di mice. Pharmacogenetic suppression of mesolimbic dopaminergic neurons significantly decreased scratching behaviors. Under the itch condition with scratching behaviors restricted by an Elizabethan collar, the induction of ΔFosB was found mostly in corticotropin-releasing hormone (CRH)-containing neurons of the hypothalamic paraventricular nucleus (PVN). These findings suggest that repetitive abnormal scratching behaviors under acute and chronic itch stimuli may activate mesolimbic dopamine neurons along with pleasant emotions, while the restriction of such scratching behaviors may initially induce the activation of PVN-CRH neurons associated with stress.
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