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Neuropathic pain and cognitive impairment are among the HIV-related conditions that have most stubbornly resisted amelioration by virally suppressive antiretroviral therapy. Overlaps between the regional brain substrates and mechanisms of neuropathic pain and cognitive disorders are increasingly recognized, yet no studies have examined the longitudinal relationship between these two disorders. Participants in the prospective, observational CNS HIV AntiRetroviral Therapy Effects Research (CHARTER) cohort underwent standardized clinical evaluations for clinical examination findings of distal sensory polyneuropathy, reporting distal neuropathic pain and neurocognitive performance at study entry (baseline) and an average of 12 years later. Change in neuropathic pain and neuropathy status from baseline to follow-up was by self-report and repeat examination, and change in neurocognitive performance was assessed using a previously published summary regression-based change score. Relationships between incident or worsened neuropathic pain and neurocognitive change were evaluated using uni- and multivariable regressions, including age at baseline and other relevant covariates. Participants were 385 people with HIV, 91 (23.6%) females, mean ± standard deviation (SD) age at baseline 43.5 (7.81) years, ethnicity 44.9% African American, 10.6% Hispanic, 42.6% non-Hispanic white and 1.82% other. Baseline median (interquartile range) nadir CD4 was 175 (34 309) cells/µl and current CD4 was 454 (279 639). Incident or worsened distal neuropathic pain occurred in 98 (25.5%) over the follow-up period. People with HIV with incident or worsened distal neuropathic pain had significantly worsened neurocognitive performance at follow-up compared to those without incident or worsened distal neuropathic pain (summary regression-based change score mean ± SD -0.408 ± 0.700 versus -0.228 ± 0.613; P = 0.0158). This effect remained significant when considering viral suppression on antiretroviral therapy, incident diabetes and other covariates as predictors. Overall neurocognitive change related to neuropathic pain was driven primarily by changes in the domains of executive function and speed of information processing. Those with incident distal neuropathy signs did not have neurocognitive worsening, nor did individuals who used opioid analgesics or other pain-modulating drugs such as amitriptyline. Worsened neurocognitive performance in people with HIV was associated with worsened neuropathic pain but not with changes in physical signs of neuropathy, and this was not attributable to therapies for pain or depression or to differences in viral suppression. This finding implies that incident or worsened pain may signal increased risk for neurocognitive impairment, and deserves more investigation, particularly if better pain management might stabilize or improve neurocognitive performance.
Learn More >The aim of this study is to report on the extent and range of the research evaluating cognitive behaviour therapy (CBT) in adults with spinal cord injury.
Learn More >The specific adenosine A3 receptor (A3AR) agonist (CF101) has potential for inflammation and pain in various disease, such as arthritis, cancer and neuropathic pain, while the role of A3AR in post-traumatic OA and the underlying mechanism is largely unknown. CF101 was orally administrated in OA rats induced by anterior cruciate ligament transection (ACLT) surgery, and the rat primary chondrocytes were stimulated by hydrogen peroxide (H O , 300 μM). Histologic grading system was performed for detecting cartilage degeneration and immunohistochemistry for determining pyroptosis. The moleculars associated with cartilage homeostasis and inflammatory cytokines were analysed; moreover, the activation of NLRP3 inflammasome was determined. CF101 treatment significantly attenuated OA cartilage damage, OA-related pain and cartilage pyroptosis. Chondrocytes stimulated by H O evoked ROS release, thereby promoting the activation of NLRP3 inflammasome and facilitating the cleavage of GSDMD, which ultimately resulted in the mass release of pro-inflammatory cytokines including IL-1β and IL-18, and production of matrix hydrolase. The pre-treatment with CF101 powerfully inhibited the above process both in vivo and in vitro. Our findings demonstrated that activation of A3AR attenuates OA progression and relieves pain perception through suppression of cartilage degradation and inhibition of ROS/NLRP3/GSDMD signalling, indicating pyroptosis is a potential candidate for OA treatment.
Learn More >The objective of this study was to test the superiority of multidisciplinary approach, that is, Short-Term Psychodynamic Psychotherapy (STPP) plus drug of choice, versus monotherapy, that is, OnabotulinumtoxinA (OnaBoNT-A).
Learn More >EEG-based neurofeedback uses mental behaviours (MB) to enable voluntary self-modulation of brain activity, and has potential to relieve central neuropathic pain (CNP) after a spinal cord injury (SCI). This study aimed to understand neurofeedback learning and the relationship between MB and neurofeedback success. Twenty-five non-CNP participants and ten CNP participants received neurofeedback training (reinforcing 9-12 Hz; suppressing 4-8 Hz and 20-30 Hz) on four visits. Participants were interviewed about the MB they used after each visit. Questionnaires examined the following factors: self-efficacy, locus of control, motivation, and workload of neurofeedback. MB were grouped into mental strategies (a goal-directed mental action) and affect (emotional experience during neurofeedback). Successful non-CNP participants significantly used more imagination-related MS and reported more negative affect compared to successful CNP participants. However, no mental strategy was clearly associated with neurofeedback success. There was some association between the lack of success and negative affect. Self-efficacy was moderately correlated with neurofeedback success (r = < 0.587, p = < 0.020), whereas locus of control, motivation, and workload had low, non-significant correlations (r < 0.300, p > 0.05). Affect may be more important than mental strategies for a successful neurofeedback performance. Self-efficacy was associated with neurofeedback success, suggesting that increasing confidence in one's neurofeedback abilities may improve neurofeedback performance.
Learn More >Patients with prurigo nodularis (PN) have multiple itchy nodules, impaired quality of life, and sleep deprivation. PN patients have a high burden of disease, primarily due to the intensity of the itch. It is reasonable to expect that rapid relief of itch – and associated improvement of sleep – are highly valued clinical outcomes for patients. Nemolizumab is an IL-31A-receptor inhibitor that modulates the neuroimmune response with reported positive efficacy and safety data in a phase 2 study of PN METHODS: Post-hoc analysis of a phase 2 trial of nemolizumab 0.5 mg/kg SC versus placebo in patients (n=70) with moderate to severe PN (≥20 nodules) and severe pruritus (NRS ≥ 7). Time to significant reduction was assessed for pruritus and sleep disturbance (SD), also assessed was scratching time during sleep.
Learn More >Carbon monoxide (CO) has long been considered a toxic gas but is now a recognized bioactive gasotransmitter with potent immunomodulatory effects. Although inhaled CO is currently under investigation for use in patients with lung disease, this mode of administration can present clinical challenges. The capacity to deliver CO directly and safely to the gastrointestinal (GI) tract could transform the management of diseases affecting the GI mucosa such as inflammatory bowel disease or radiation injury. To address this unmet need, inspired by molecular gastronomy techniques, we have developed a family of gas-entrapping materials (GEMs) for delivery of CO to the GI tract. We show highly tunable and potent delivery of CO, achieving clinically relevant CO concentrations in vivo in rodent and swine models. To support the potential range of applications of foam GEMs, we evaluated the system in three distinct disease models. We show that a GEM containing CO dose-dependently reduced acetaminophen-induced hepatocellular injury, dampened colitis-associated inflammation and oxidative tissue injury, and mitigated radiation-induced gut epithelial damage in rodents. Collectively, foam GEMs have potential paradigm-shifting implications for the safe therapeutic use of CO across a range of indications.
Learn More >Effective treatments for chronic pain remain limited. Conceptually, a closed-loop neural interface combining sensory signal detection with therapeutic delivery could produce timely and effective pain relief. Such systems are challenging to develop because of difficulties in accurate pain detection and ultrafast analgesic delivery. Pain has sensory and affective components, encoded in large part by neural activities in the primary somatosensory cortex (S1) and anterior cingulate cortex (ACC), respectively. Meanwhile, studies show that stimulation of the prefrontal cortex (PFC) produces descending pain control. Here, we designed and tested a brain-machine interface (BMI) combining an automated pain detection arm, based on simultaneously recorded local field potential (LFP) signals from the S1 and ACC, with a treatment arm, based on optogenetic activation or electrical deep brain stimulation (DBS) of the PFC in freely behaving rats. Our multiregion neural interface accurately detected and treated acute evoked pain and chronic pain. This neural interface is activated rapidly, and its efficacy remained stable over time. Given the clinical feasibility of LFP recordings and DBS, our findings suggest that BMI is a promising approach for pain treatment.
Learn More >Chronic postsurgical pain (CPSP) is a common and disabling postoperative complication. Several risk factors for CPSP have been established, but it is unclear whether they are significant for any type of surgery. This systematic review aimed to assess the risk of CPSP related to three known preoperative risk factors "age, sex and preoperative pain" in the adult population after any type of elective non-obstetrical surgery.
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