Pain
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Understanding the mechanisms that underpin the transition from acute to chronic pain is critical for the development of more effective and targeted treatments. There is growing interest in the contribution of glial cells to this process, with cross-sectional preclinical studies demonstrating specific changes in these cell types capturing targeted timepoints from the acute phase and the chronic phase. In vivo longitudinal assessment of the development and evolution of these changes in experimental animals and humans has presented a significant challenge. ⋯ These advances now permit tracking of glial changes over time and provide the ability to relate these changes to pain-relevant symptomology, comorbid psychiatric conditions, and treatment outcomes at both a group and an individual level. In this article, we summarize evidence for gliosis in the transition from acute to chronic pain and provide an overview of the specific radiotracers available to measure this process, highlighting their potential, particularly when combined with ex vivo / in vitro techniques, to understand the pathophysiology of chronic neuropathic pain. These complementary investigations can be used to bridge the existing gap in the field concerning the contribution of gliosis to neuropathic pain and identify potential targets for interventions.
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Exercise is a first-line treatment for chronic low back pain (CLBP), reducing pain and disability in the short term. However, exercise benefits decrease over time, with a lack of long-term exercise adherence a potential reason for this. This study aimed to synthesize the perceptions and beliefs of individuals with CLBP and identify their barriers and enablers to exercise adherence. ⋯ These themes contained 16 subthemes that were predominantly both barriers and enablers to exercise adherence. The individual's experiences of barriers and enablers were most appropriately represented across a spectrum, where influencing factors could be a barrier or enabler to exercise adherence, and these could be specific to pre-exercise, during-exercise, and post-exercise situations. These findings may be used to improve exercise adherence and ultimately treatment outcomes in people with CLBP.
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Adverse childhood experiences (ACEs) affect approximately half of all children worldwide. These experiences have been linked to increased pain sensitivity in adulthood and a higher likelihood of developing severe chronic pain. However, most studies have assessed the effects of ACEs retrospectively, long after they occurred, leaving room for other factors to influence the observed outcomes. ⋯ Children with higher PTSS severity displayed pain hypersensitivity regardless of their traumatic exposure level, whereas in children with lower PTSS severity, greater traumatic exposure correlated with pain hypersensitivity. The results suggest that ACEs among children lead to concurrent pain hypersensitivity and distress and may put them at elevated risk of chronic pain early in life. In addition, our findings emphasize the need for identifying children with various PTSS levels to provide tailored interventions and mitigate the long-term negative effects of ACEs.
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Growing evidence from pharmacovigilance data and postmortem toxicology reports highlights the misuse potential of gabapentinoids. This study aimed to investigate the risk of serious adverse outcomes (drug misuse, overdose, major trauma), and their risk factors, in primary care patients who are prescribed gabapentinoids. Using the UK Clinical Practice Research Datalink, a matched cohort study calculated adverse event rates separately for gabapentinoid-exposed and unexposed cohorts. ⋯ The association with overdose was stronger for pregabalin than gabapentin. All adverse outcomes were significantly associated with smoking, history of substance misuse, overdose, or a mental health condition and prescription of opioids, benzodiazepines, antidepressants, and Z-drug hypnotics (eg, gabapentin hazard ratios for association of concurrent opioid use: misuse 1.49 [1.47-1.51]; overdose 1.87 [1.78-1.96]; major trauma 1.28 [1.26-1.30]). Our findings highlight the importance of careful patient selection when prescribing gabapentinoids and the need to educate prescribers about the risks of these drugs, particularly in combination with other central nervous system depressants.
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Neuropathic pain is a debilitating chronic condition that remains difficult to treat. More efficacious and safer therapeutics are needed. A potential target for therapeutic intervention recently identified by our group is the G-protein coupled receptor 160 (GPR160) and the cocaine- and amphetamine-regulated transcript peptide (CARTp) as a ligand for GPR160. ⋯ Cocaine- and amphetamine-regulated transcript peptide-induced behavioral hypersensitivities are independent of receptor-interacting protein kinase 2 (RIPK2), a common adaptor protein to NOD2. Immunofluorescence studies found NOD2 co-expressed with endothelial cells rather than glial cells, implicating potential roles for CARTp/NOD2 signaling in these cells. While these findings are based only on studies with male mice, our results identify a novel pathway by which CARTp causes behavioral hypersensitivities in the DH-SC through NOD2 and highlights the importance of NOD2-mediated responses in nonpathogenic settings.