Pain
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Expectations modulate the subjective experience of pain by increasing sensitivity to nociceptive inputs, an effect mediated by brain regions such as the insula. However, it is still unknown whether the neural structures underlying pain expectancy hold sensory-specific information or, alternatively, code for modality-independent features (eg, unpleasantness), potentially common with other negative experiences. We used functional magnetic resonance imaging to investigate neural activity underlying the expectation of different, but comparably unpleasant, pain and disgust. ⋯ At the brain level, this effect was mediated by the intermediate dysgranular section of the insula, whereas it was suppressed by more anterior agranular portions of the same region. Instead, no expectancy modulation was observed when the modality of the cue differed from that of the subsequent stimulus. Our data suggest that the insular cortex encodes prospective aversive events in terms of their modality-specific features, and whether they match with subsequent stimulations.
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Voltage-gated potassium (Kv) channels are increasingly recognised as key regulators of nociceptive excitability. Kcns1 is one of the first potassium channels to be associated with neuronal hyperexcitability and mechanical sensitivity in the rat, as well as pain intensity and risk of developing chronic pain in humans. Here, we show that in mice, Kcns1 is predominantly expressed in the cell body and axons of myelinated sensory neurons positive for neurofilament-200, including Aδ-fiber nociceptors and low-threshold Aβ mechanoreceptors. ⋯ After neuropathic injury, Kcns1 KO mice exhibited exaggerated mechanical pain responses and hypersensitivity to both noxious and innocuous cold, consistent with increased A-fiber activity. Interestingly, Kcns1 deletion also improved locomotor performance in the rotarod test, indicative of augmented proprioceptive signalling. Our results suggest that restoring Kcns1 function in the periphery may be of some use in ameliorating mechanical and cold pain in chronic states.
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Concerns over prescription opioids contributing to high levels of opioid use disorder and overdose have led policymakers and clinicians to seek means to reduce inappropriate and high-dose initial prescriptions. To inform such efforts, we sought to describe the clinical indications associated with opioid initiation and the characteristics of the initial prescriptions and patients through a retrospective population-based cohort study. Our cohort included Ontarians initiating prescription opioids for pain management between April 1, 2015, and March 31, 2016. ⋯ Individuals with postsurgical pain received the highest daily doses (40.5% with greater than 50 milligram morphine equivalent), and those with musculoskeletal pain received more initial prescriptions with a duration exceeding 7 days (34.2%). Opioids are initiated for a wide range of indications with varying doses and durations; yet, those who initiated opioids for postsurgical and musculoskeletal pain received the greatest doses and durations of therapy, respectively. These findings may help tailor and prioritize efforts to promote more appropriate opioid prescribing.
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Existing evidence of an association between effort-reward imbalance (ERI) at work and musculoskeletal pain is limited, preventing reliable conclusions about the magnitude and direction of the relation. In a large longitudinal study, we examined whether the onset of ERI is associated with subsequent onset of musculoskeletal pain among those free of pain at baseline, and vice versa, whether onset of pain leads to onset of ERI. Data were from the Swedish Longitudinal Occupational Survey of Health (SLOSH) study. ⋯ In the adjusted models, onset of ERI was associated with onset of neck-shoulder pain (relative risk [RR] 1.51, 95% confidence interval [CI] 1.21-1.89) and low back pain (RR 1.21, 95% CI 0.97-1.50). The opposite was also observed, as onset of neck-shoulder pain increased the risk of subsequent onset of ERI (RR 1.36, 95% CI 1.05-1.74). Our findings suggest that when accounting for the temporal order, the associations between ERI and musculoskeletal pain that affects life are bidirectional, implying that interventions to both ERI and pain may be worthwhile to prevent a vicious cycle.
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Peripheral nerve injury causes maladaptive plasticity in the central nervous system and induces chronic pain. In addition to the injured limb, abnormal pain sensation can appear in the limb contralateral to the injury, called mirror image pain. Because synaptic remodeling in the primary somatosensory cortex (S1) has critical roles in the induction of chronic pain, cortical reorganization in the S1 ipsilateral to the injured limb may also accompany mirror image pain. ⋯ When local inhibitory circuits were blocked, astrocyte-dependent spine plasticity and allodynia were revealed. Thus, we propose that cortical astrocytes prime the induction of spine plasticity and mirror image pain after peripheral nerve injury. Moreover, this result suggests that cortical synaptic rewiring could be sufficient to cause allodynia on the uninjured periphery.