Pain
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Randomized Controlled Trial
Differential neurophysiological correlates of bottom-up and top-down modulations of pain.
The perception of pain is highly variable. It depends on bottom-up-mediated factors like stimulus intensity and top-down-mediated factors like expectations. In the brain, pain is associated with a complex pattern of neuronal responses including evoked potentials and induced responses at alpha and gamma frequencies. ⋯ In contrast, placebo analgesia was associated with changes of evoked potentials, but not of alpha and gamma responses. These findings reveal that pain-related neuronal responses are differentially sensitive to bottom-up and top-down modulations of pain, indicating that they provide complementary information about pain perception. The results further show that pain-induced gamma oscillations do not invariably encode pain perception but may rather represent a marker of sensory processing whose influence on pain perception varies with behavioral context.
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Depression is associated with receipt of higher doses of prescription opioids. It is not known whether the reverse association exists in that an increased opioid dose is associated with increased depression. Questionnaires were administered to 355 patients with chronic low back pain at baseline and 1-year and 2-year follow-up. ⋯ Post hoc analysis revealed that depression was significantly associated with a 10.1-mg MED increase in fully adjusted models. Change to a higher MED leads to an increased risk of depression, and developing depression increases the likelihood of a higher MED. We speculate that treating depression or lowering MED may mitigate a bidirectional association and ultimately improve pain management.
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Ankylosing spondylitis is associated with back pain and fatigue and impacts mobility but can be treated with tumor necrosis factor inhibitors (TNFi). The differential effects of TNFi treatment on multiple symptoms and the brain is not well delineated. Thus, we conducted a 2-part study. ⋯ Pain intensity reduction was associated with cortical thinning of the secondary somatosensory cortex, and pain unpleasantness reduction was associated with the cortical thinning of motor areas. In contrast, fatigue reduction correlated with cortical thinning of the insula, primary sensory cortex/inferior parietal sulcus, and superior temporal polysensory areas. This indicates that TNFi treatment produces changes in brain areas implicated in sensory, motor, affective, and cognitive functions.
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Little is known about variability in primary care providers' (PCPs) adherence to opioid-monitoring guidelines for patients. We examined variability of adherence to monitoring guidelines among PCPs and ascertained the relationship between PCP adherence and opioid misuse by their patients. We included primary care patients receiving long-term opioids (≥3 prescriptions within 6 months) for chronic noncancer pain and PCPs with ≥4 eligible patients. ⋯ Primary care providers varied significantly in adherence to opioid prescription guidelines. Increased patient risk was associated with increased monitoring and with greater misuse. Future work should study system-level interventions to enable clinical monitoring and support opioid guideline adherence.
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Presynaptic inhibition of optogenetically identified VGluT3+ sensory fibres by opioids and baclofen.
Distinct subsets of sensory nerve fibres are involved in mediating mechanical and thermal pain hypersensitivity. They may also differentially respond to analgesics. Heat-sensitive C-fibres, for example, are thought to respond to μ-opioid receptor (MOR) activation while mechanoreceptive fibres are supposedly sensitive to δ-opioid receptor (DOR) or GABAB receptor (GABABR) activation. ⋯ Baclofen, in striking contrast, powerfully inhibited all fibre populations investigated. In summary, we report optogenetic stimulation of DRG neurons in spinal slices as a capable approach for the subtype-selective investigation of primary afferent nerve fibres. Overall, pharmacological accessibility of different subtypes of sensory fibres considerably overlaps, indicating that MOR, DOR, and GABABR expressions are not substantially segregated between heat and mechanosensitive fibres.