Browse by Audience
Chronic pain affects 50% of adults with sickle cell disease (SCD). Although inflammation is thought to contribute to the pathogenesis of chronic pain, no studies have examined the differences in circulating cytokines between patients with SCD with and without chronic pain. We performed an observational cohort study using blood and urine samples from adults with SCD with and without chronic pain at their usual state of health. We tested the hypothesis that, compared to those without chronic pain, those with chronic pain would have significantly higher baseline circulating proinflammatory cytokines. A total of 61 adults with SCD, 40 with chronic pain and 21 without chronic pain were tested. When SCD patients with chronic pain were compared to those without chronic pain, no significant differences in cytokine levels were noted. The variables most associated with the diagnosis of chronic pain in this population were opioid dose and subject age.
Learn More >Epoxyeicosatrienoic acids (EET) and related epoxy fatty acids (EpFA) are endogenous anti-inflammatory compounds, which are converted by the soluble epoxide hydrolase (sEH) to dihydroxylethersatrienoic acids (DHETs) with lessened biological effects. Inhibition of sEH is used as a strategy to increase EET levels leading to lower inflammation. Rheumatoid arthritis is a chronic autoimmune disease that leads to destruction of joint tissues. This pathogenesis involves a complex interplay between the immune system, and environmental factors. Here, we investigate the effects of inhibiting sEH with 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU) on a collagen-induced arthritis model. The treatment with TPPU ameliorates hyperalgesia, edema, and decreases the expression of important pro-inflammatory cytokines of Th1 and Th17 profiles, while increasing Treg cells. Considering the challenges to control RA, this study provides robust data supporting that inhibition of the sEH is a promising target to treat arthritis.
Learn More >Meniscal injury is a common prelude to post-traumatic osteoarthritis (PTOA). Joint nerves can become damaged in arthritic joints leading to the manifestation of neuropathic pain. Both PTOA and neuropathic pain are more common in females; however, it is unknown whether the neural processing of joint pain is sex-specific.
Learn More >Nucleoside reverse transcriptase inhibitors (NRTIs) are associated with the development of painful neuropathies and may further aggravate sensory neuropathy produced by HIV-1 infection, leading to discontinuation of NRTI therapy by HIV patients. Following antiretroviral-induced peripheral neuropathy, c-Jun N-terminal kinase (JNK) is activated in the dorsal root ganglia (DRG) and spinal cord. However, the contribution of individual JNK genes remains unknown. Here, we have tested the behavioural mechanical sensitivity of JNK1, JNK2 and JNK3 knockout (KO) mice in the von Frey test after treatment with 2',3'-dideoxycytidine (ddC). Protein expression was investigated in the spinal cord of wild type (wt) and KO mice by western blotting. The onset of neuropathic pain was prevented by the deletion of JNK3, leading us to hypothesize that JNK3 protein plays a major role in the regulation of pain threshold in antiretroviral neuropathy. The growth-associated protein 43 (GAP-43) and the transcription factor c-Jun are involved in regeneration processes. This study revealed an up-regulation of GAP-43 and c-Jun protein, 14 days after ddC administration. JNK1 deletion induced a significant reduction in c-Jun phosphorylation and GAP-43 protein contents. In contrast, there was no difference in ddC-induced reduction of hind paw intraepidermal nerve fibre density in all JNK KO mice. Overall, these findings indicate that JNK3 plays a critical role in regulating ddC neurotoxicity-induced mechanical pain hypersensitivity, while JNK1 is important for activation of c-Jun and GAP-43 as a critical pathway of a regeneration program. These data highlight the impact of individual JNK isoforms on antiretroviral neurotoxicity and neuro-regeneration processes.
Learn More >Longitudinal cohort study with 13-year follow-up.
Learn More >Headache disorders like migraine show geographic and ethnic differences between Asian and European/North American countries. In cluster headache, these differences are rarely mentioned and discussed. This article aimed to review the characteristics of cluster headache in Asian countries and compare the clinical features to those in European and North American populations.
Learn More >Background Migraine is a common disorder with high social and medical impact. Patients with migraine have a much higher chance of experiencing headache attacks as compared to the general population. Recent neuroimaging studies have confirmed that pathophysiology in the brain is not limited to the moment of the attack but is also present in between attacks, the interictal phase. Methods In this study, we hypothesized that the topology of functional brain networks is also different in the interictal state, compared to people who are not affected by migraine. We also expected that the level of network disturbances scales with the number of years people have suffered from migraine. Functional connectivity between 78 cortical brain regions was estimated for source-level magnetoencephalography (MEG) data by calculating the Phase Lag Index (PLI), in five frequency bands (delta-beta), and compared between healthy controls (n=24), and patients who had been suffering from migraine longer than 6 years (n=12) or shorter than 6 years (n=12). Moreover, the topology of the functional networks was characterized using the Minimum Spanning Tree (MST). Results The migraine groups did not differ from each other in functional connectivity. However, the network topology was different as compared to healthy controls. The results were frequency specific, and higher average nodal betweenness centrality was specifically evident in higher frequency bands in patients with a longer disease duration, while an opposite trend was present for lower frequencies. Conclusion This study shows that patients with migraine have a different network topology in the resting-state as compared to healthy controls, whereby specific brain areas have altered topological roles in a frequency specific manner. Some alterations appear specifically in patients with long-term migraine, which might show the long-term effects of the disease.
Learn More >Adults with sleep problems are at higher risk for onset of musculoskeletal pain, but the evidence is less clear for children. This prospective cohort study investigated whether children with sleep problems are at higher risk for onset of musculoskeletal pain and explored whether sex is a modifier of this association. In a prospective cohort study of Australian schoolchildren (n = 1239, mean age 9 years), the associations between sleep problems at baseline and new onset of both musculoskeletal pain and persistent musculoskeletal pain (pain lasting > 3 months) 1 year later were investigated using logistic regression. The potential modifying effect of sex was also assessed. One-year incidence proportion for musculoskeletal pain onset is 43% and 7% for persistent musculoskeletal pain. Sleep problems were associated with musculoskeletal pain onset and persistent musculoskeletal pain onset in boys, odds ratio 2.80 (95% CI 1.39, 5.62) and OR 3.70 (1.30, 10.54), respectively, but not girls OR 0.58 (0.28, 1.19) and OR 1.43 (0.41, 4.95), respectively.Conclusions: Rates of musculoskeletal pain are high in children. Boys with sleep problems are at greater risk of onset of musculoskeletal pain, but girls do not appear to have higher risk. Consideration of sleep health may help prevent persistent musculoskeletal pain in children.What is Known:• Sleep problems are associated with the onset of musculoskeletal pain in adults.• It is not clear if the association between sleep problems and the onset of musculoskeletal pain is present also in children and if sex plays a role in this association.What is New:• This is the first large population-based study that has prospectively investigated the relationship between sleep problems and onset of musculoskeletal pain in school-aged children.• Children, especially boys with sleep problems, were at increased risk for the development of persistent musculoskeletal pain.
Learn More >Brain-derived neurotrophic factor (BDNF), a major focus for regenerative therapeutics, has been lauded for its pro-survival characteristics and involvement in both development and recovery of function within the central nervous system (CNS). However, studies of tyrosine receptor kinase B (TrkB), a major receptor for BDNF, indicate that certain effects of the TrkB receptor in response to disease or injury may be maladaptive. More specifically, imbalance among TrkB receptor isoforms appears to contribute to aberrant signaling and hyperpathic pain. A truncated isoform of the receptor, TrkB.T1, lacks the intracellular kinase domain of the full length receptor and is up-regulated in multiple CNS injury models. Such up-regulation is associated with hyperpathic pain, and TrkB.T1 inhibition reduces neuropathic pain in various experimental paradigms. Deletion of TrkB.T1 also limits astrocyte changes in vitro, including proliferation, migration, and activation. Mechanistically, TrkB.T1 is believed to act through release of intracellular calcium in astrocytes, as well as through interactions with neurotrophins, leading to cell cycle activation. Together, these studies support a potential role for astrocytic TrkB.T1 in hyperpathic pain and suggest that targeted strategies directed at this receptor may have therapeutic potential.
Learn More >