Pain
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The rostral ventromedial medulla (RVM) is a crucial structure in the descending pain modulatory system, playing a key role as a relay for both the facilitation and inhibition of pain. The chronic social defeat stress (CSDS) model has been widely used to study stress-induced behavioral impairments associated with depression in rodents. Several studies suggest that CSDS also causes changes related to chronic pain. ⋯ In addition, RVM inhibition in animals exposed to a subthreshold social defeat stress protocol induces a susceptible phenotype, facilitating all stress outcomes. Finally, chronic RVM inhibition-without any social stress stimulus-induces chronic pain but not depressive-like behaviors. Our findings provide insights into the comorbidity between chronic pain and depression by indicating the involvement of the RVM in establishing social stress-induced behavioral responses associated with both chronic pain and depression.
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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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Negative attitudes/beliefs surrounding osteoarthritis, pain, and activity contribute to reduced physical activity in people with knee osteoarthritis (KOA). These attitudes/beliefs are assessed using self-report questionnaires, relying on information one is consciously aware of and willing to disclose. Automatic (ie, implicit) assessment of attitudes does not rely on conscious reflection and may identify features unique from self-report. ⋯ Correlations between implicit and self-reported measures were nonsignificant or weak (rho = -0.29 to 0.19, P < 0.001 to P = 0.767). People with painful KOA hold heightened implicit threat-activity associations, capturing information unique to that from self-report questionnaires. Evaluating links between implicit threat-activity associations and real-world behaviour, including physical activity levels, is warranted.
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Visuospatial perception is thought to be adaptive-ie, hills are perceived as steeper when capacity is low, or threat is high-guiding appropriate interaction with the environment. Pain (bodily threat) may similarly modulate visuospatial perception, with the extent of modulation influenced by threat magnitude (pain intensity, fear) and associated with behaviour (physical activity). We compared visuospatial perception of the environment between 50 people with painful knee osteoarthritis and 50 age-/sex-matched pain-free control participants using 3 virtual reality tasks (uphill steepness estimation, downhill steepness estimation, and a distance-on-hill measure), exploring associations between visuospatial perception, clinical characteristics (pain intensity, state and trait fear), and behaviour (wrist-worn accelerometry) within a larger knee osteoarthritis group (n = 85). ⋯ Results were unchanged in a replication analysis using all knee osteoarthritis participants (n = 85), except the downhill steepness interaction was no longer significant. In people with knee osteoarthritis, higher state fear was associated with greater over-estimation of downhill slope steepness (rho = 0.69, P < 0.001), and greater visuospatial overestimation (distance-on-hill) was associated with lower physical activity levels (rho = -0.22, P = 0.045). These findings suggest that chronic pain may shift perception of the environment in line with protection, with overestimation heightened when threat is greater (steeper hills, more fearful), although impact on real-world behaviour is uncertain.
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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.