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Individually unique dynamics of cortical connectivity reflect the ongoing intensity of chronic pain.
Chronic pain diseases are characterised by an ongoing and fluctuating endogenous pain, yet it remains to be elucidated how this is reflected by the dynamics of ongoing functional cortical connections.Here, we investigated the cortical encoding of 20 chronic back pain patients and 20 chronic migraineurs in four repeated fMRI sessions. A brain parcellation approach subdivided the whole brain into 408 regions. Linear mixed effects models were fitted for each pair of brain regions to explore the relationship between the dynamic cortical connectivity and the observed trajectory of the patients' ratings of fluctuating endogenous pain.Overall, we found that periods of high and increasing pain were predominantly related to low cortical connectivity. The change of pain intensity in chronic back pain was subserved by connections in left parietal opercular regions, right insular regions, as well as large parts of the parietal, cingular and motor cortices. The change of pain intensity direction in chronic migraine was reflected by decreasing connectivity between the anterior insular cortex and orbitofrontal areas, as well as between the PCC and frontal and ACC regions.Interestingly, the group results were not mirrored by the individual patterns of pain-related connectivity, which is suggested to deny the idea of a common neuronal core problem for chronic pain diseases. The diversity of the individual cortical signatures of chronic pain encoding results adds to the understanding of chronic pain as a complex and multifaceted disease. The present findings support recent developments for more personalised medicine.
Learn More >This exploratory study investigates if intra-articular injected gold microparticles in knee osteoarthritis (KOA) reduce immunomodulatory-based pain via proteomic changes in the synovial fluid (SF) and serum.
Learn More >Effective, rigorously evaluated nonpharmacological treatments for chronic pain are needed. This study compared the effectiveness of training in hypnosis (HYP) and mindfulness meditation (MM) to an active education control (ED). Veterans (N=328) were randomly assigned to 8 manualized, group-based, in-person sessions of HYP (n = 110), MM (n = 108), or ED (n = 110). Primary (average pain intensity; API) and secondary outcomes were assessed at pretreatment, posttreatment, and 3- and 6-months posttreatment. Treatment effects were evaluated using linear regression, a generalized estimating equation approach, or a Fisher exact test, depending on the variable. There were no significant omnibus between-group differences in pre- to posttreatment change in API, however pre- to posttreatment improvements in API and several secondary variables were seen for participants in all three conditions. Participation in MM resulted in greater decreases in API and pain interference at 6-months posttreatment relative to ED. Participation in HYP resulted in greater decreases in API, pain interference, and depressive symptoms at 3- and 6-months posttreatment compared to ED. No significant differences on outcomes between HYP and MM were detected at any time point. This study suggests that all three interventions provide posttreatment benefits on a range of outcomes, but the benefits of HYP and MM continue beyond the end of treatment, while the improvements associated with ED dissipate over time. Future research is needed to determine whether the between-group differences that emerged posttreatment are reliable, whether there are benefits of combining treatments, and to explore moderating and mediating factors.
Learn More >The ObserVational survey of the Epidemiology, tReatment and Care of MigrainE (OVERCOME; United States) study is a multicohort, longitudinal web survey that assesses symptomatology, consulting, diagnosis, treatment, and impact of migraine in the United States.
Learn More >Following surgical repair after peripheral nerve injury, neuropathic pain diminishes in most patients, but can persist in a small proportion of cases the mechanism of which remains poorly understood. Based on the spared nerve injury (SNI), we developed a rat nerve repair (NR) model, where a delayed reconstruction of the SNI injured nerves resulted in alleviating chronic pain-like behavior only in a subpopulation of rats. Multiple behavioral measures were assayed over 11-week pre- and post-surgery periods (tactile allodynia, pain prick responses, sucrose preference, motor coordination, cold allodynia) in SNI (n=10), sham (n=8), and NR (n=12) rats. All rats also underwent resting-state- fMRI under anesthesia at multiple timepoints post-surgery, and at 10-weeks histology and retrograde labeling was used to calculate peripheral reinnervation. Behavioral measures indicated that at about 5-weeks post-surgery the NR group separated to pain persisting (NR-persisting, n=5) and recovering groups (NR-recovering, n=7). Counts of afferent nerves and of DRG cells were not different between NR groups. Therefore, NR group differences could not be explained by peripheral reorganization. In contrast, large brain functional connectivity differences were observed between NR groups, where corticolimbic reorganization paralleled with pain recovery (repeat measure ANOVA, false discovery rate, p <0.05), and functional connectivity between accumbens and medial frontal cortex was related both to tactile allodynia (nociception) and to sucrose preference (anhedonia) in NR group. Our study highlights the importance of brain circuitry in the reversal of neuropathic pain as a natural pain-relieving mechanism. Further studies regarding the therapeutic potentials of these processes are warranted.
Learn More >The purpose of this study was to propose a definition of "wearing off" at the individual patient-level and determine the percentage of patients with migraine who experience "wearing off" of efficacy of galcanezumab at the end of a treatment cycle using this predefined threshold.
Learn More >Post-burn pruritus is a significant issue that can have a devastating impact on patient quality of life. Despite its known negative impact, few studies have focused on the pediatric population. Thus, the aim of this study was to determine the incidence of pruritus among pediatric burn patients as well as identify its predictive factors and commonly used treatments, including the novel use of laser therapy. A retrospective analysis of all burn patients treated at our pediatric burn centre from 2009 to 2017 was conducted. The primary outcome measure was the presence or absence of pruritus at any point following the burn. One thousand seven hundred and eighty-three patients met the inclusion criteria for this study. The mean age at injury was 3.67 years (SD 4.02) and the mean burn TBSA was 3.48% (SD 4.81) with most burns resulting from scalds (66%). In total, 665 patients (37.3%) experienced pruritus. Following multivariable logistic regression, TBSA, age > 5 years, burns secondary to fire/flames, and burn depth, were identified as significant predictors of pruritus (p < 0.05). Pruritus was treated with diphenhydramine (85.0%), hydroxyzine (37.3%), and gabapentin (4.2%) as well as massage (45.7%), pressure garments (20.0%), and laser therapy (8.6%). This study addresses the knowledge gap in literature related to post-burn pruritus among pediatric patients and includes one of the largest patient cohorts published to date. Moreover, the results further contribute to our understanding of post-burn pruritus in children and may help us to predict which patients are most likely to be affected, so that treatment can be initiated as soon as possible.
Learn More >Inflammatory pain, such as hypersensitivity resulting from surgical tissue injury, occurs as a result of interactions between the immune and nervous systems with the orchestrated recruitment and activation of tissue-resident and circulating immune cells to the site of injury. Our previous studies identified a central role for Ly6C myeloid cells in the pathogenesis of postoperative pain. We now show that the chemokines CCL17 and CCL22, with their cognate receptor CCR4, are key mediators of this response. Both chemokines are up-regulated early after tissue injury by skin-resident dendritic and Langerhans cells to act on peripheral sensory neurons that express CCR4. CCL22, and to a lesser extent CCL17, elicit acute mechanical and thermal hypersensitivity when administered subcutaneously; this response abrogated by pharmacological blockade or genetic silencing of CCR4. Electrophysiological assessment of dissociated sensory neurons from naïve and postoperative mice showed that CCL22 was able to directly activate neurons and enhance their excitability after injury. These responses were blocked using C 021 and small interfering RNA (siRNA)-targeting CCR4. Finally, our data show that acute postoperative pain is significantly reduced in mice lacking CCR4, wild-type animals treated with CCR4 antagonist/siRNA, as well as transgenic mice depleted of dendritic cells. Together, these results suggest an essential role for the peripheral CCL17/22:CCR4 axis in the genesis of inflammatory pain via direct communication between skin-resident dendritic cells and sensory neurons, opening therapeutic avenues for its control.
Learn More >A comprehensive analysis of clinical information in patients with chronic low back pain (CLBP) was performed to clarify the clinical characteristics of geriatric LBP from the perspective of body composition, spinal alignment, and blood findings related to senescence. We enrolled 203 patients with an average age of 79.0 years (77 men and 126 women), with non-specific CLBP as a single-center prospective cohort study, the patients were compared with age- and sex-matched controls without CLBP using a propensity score-matching. We performed laboratory analysis, radiographic evaluations for global spinal parameter and lumbar degeneration, and body composition analysis using whole-body dual-energy X-ray absorptiometry. We observed a higher red blood cell distribution width (RDW) (p < 0.001), which is an index of aging, as well as a lower vitamin D level (p = 0.002), skeletal muscle mass index (p = 0.045) and a higher fat mass (p = 0.007) in patients with CLBP. Moreover, patients with geriatric CLBP had significantly lower lumbar lordosis (p = 0.024), and higher sagittal vertical axis (p = 0.006) was correlated with lower extremity and trunk muscle mass (p < 0.001), independent of lumbar degeneration. Geriatric patients with CLBP have sarcopenic fat accumulation and spinal sagittal malalignment with senescent status, such as elevated RDW and hypovitaminosis D.
Learn More >To evaluate veteran patient and provider perceptions and preferences on complementary and integrative medicine (CIM) for headache management.
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