Articles: chronic.
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Chronic pain is common in young people and can have a major life impact. Despite the burden of chronic pain, mechanisms underlying chronic pain development and persistence are still poorly understood. Specifically, white matter (WM) connectivity has remained largely unexplored in pediatric chronic pain. ⋯ Implicated tracts include both those connecting cortical and limbic structures (uncinate fasciculus, cingulum, anterior thalamic radiation), which were associated with pain catastrophizing, as well as sensorimotor tracts (corticospinal tract). By identifying alterations in the biologically informative WM microstructural metrics orientation dispersion and neurite density, our findings provide important and novel mechanistic insights for understanding the pathophysiology underlying chronic pain. Taken together, the data support alterations in fiber organization as a meaningful characteristic, contributing process to the chronic pain state.
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Neuropeptide Y (NPY) Y2 receptor (Y2) antagonist BIIE0246 can both inhibit and facilitate nociception. The authors hypothesized that Y2 function depends on inflammation or nerve injury status. ⋯ The authors conclude that Y2 at central terminals of primary afferent neurons provides tonic inhibition of mechanical and cold nociception and itch. This switches to the promotion of mechanical and thermal hyperalgesia in models of acute and chronic postsurgical and neuropathic pain, perhaps due to an increase in the population of Y2 that effectively couples to G-proteins. These results support the development of Y2 antagonists for the treatment of chronic postsurgical and neuropathic pain.
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Epigenetics has gained considerable interest as potential mediators of molecular alterations that could underlie the prolonged sensitization of nociceptors, neurons, and glia in response to various environmental stimuli. Histone acetylation and deacetylation, key processes in modulating chromatin, influence gene expression; elevated histone acetylation enhances transcriptional activity, whereas decreased acetylation leads to DNA condensation and gene repression. Altered levels of histone deacetylase (HDAC) have been detected in various animal pain models, and HDAC inhibitors have demonstrated analgesic effects in these models, indicating HDACs' involvement in chronic pain pathways. ⋯ Moreover, methodological limitations have previously impeded an in-depth study of epigenetic changes in the human brain. In this study, we employed [ 11 C]Martinostat, an HDAC-selective radiotracer, positron emission tomography to assess HDAC availability in the brains of 23 patients with chronic low back pain (cLBP) and 11 age-matched and sex-matched controls. Our data revealed a significant reduction of [ 11 C]Martinostat binding in several brain regions associated with pain processing in patients with cLBP relative to controls, highlighting the promising potential of targeting HDAC modulation as a therapeutic strategy for cLBP.
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Terpenes are small hydrocarbon compounds that impart aroma and taste to many plants, including Cannabis sativa. A number of studies have shown that terpenes can produce pain relief in various pain states in both humans and animals. However, these studies were methodologically limited and few established mechanisms of action. ⋯ We then used the adenosine A 2A receptor (A 2A R) selective antagonist istradefylline (3.2 mg/kg, IP) and spinal cord-specific CRISPR knockdown of the A 2A R to identify this receptor as the mechanism for terpene antinociception in CIPN. In vitro cAMP and binding studies and in silico modeling studies further suggested that the terpenes act as A 2A R agonists. Together these studies identify Cannabis terpenes as potential therapeutics for chronic neuropathic pain and identify a receptor mechanism for this activity.
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Chronic pain is a major global health problem. Untreated pain causes particular suffering in marginalized communities. Most studies investigating chronic pain in sub-Saharan Africa stem from South Africa and Nigeria. ⋯ The body sites most commonly affected among those with chronic pain were knees (37.2%), followed by lower back (33.7%) and head (23.3%). The data for the first time provide insights into the burden of chronic pain among Somali pastoralists and reveal associated risk factors. The results support the planning of locally adapted health interventions for pastoralist-specific pain management considering the effects of chronic pain on pastoralists' daily lives.