Pain
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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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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.
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Persistent postoperative pain is a well-established clinical problem with potential severe personal and socioeconomic implications. The prevalence of persistent pain varies across surgery types. Severe persistent pain and related impairment occur in 5% to 10% of patients after groin hernia repair. ⋯ For GCH1, the A allele of SNP rs3783641, T allele of rs8007267, and AT haplotype showed a protective effect trend (although nonsignificant; P = 0.08, 0.06, and 0.08, respectively). A prediction model of substantial PPP-related activity impairment, combining COMT and GCH1 SNPs with clinical, psychophysical, and psychological risk factors, had a "good" (0.8 < area under curve < 0.9) discriminatory power. These data suggest that functional variations in COMT and GCH1 combined with clinical factors are predictive of PPP-related impairment after groin herniotomy.
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Inoculation is one of the first and most common experiences of procedural pain in infancy. However, little is known about how needle puncture pain is processed by the central nervous system in children. In this study, we describe for the first time the event-related activity in the infant brain during routine inoculation using electroencephalography. ⋯ Both inoculation event-related potential amplitude and behavioral pain scores increased with age but the 2 measures were not correlated with each other. These components are the first recordings of brain activity in response to real-life needle pain in infants up to a year old. They provide new evidence of postnatal nociceptive processing and, combined with more traditional behavioral pain scores, offer a potentially more sensitive measure for testing the efficacy of analgesic protocols in this age group.
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The descending noradrenergic (NAergic) projection to the spinal cord forms part of an endogenous analgesic system. After nerve injury, a localised failure in this compensatory system has been implicated as a permissive factor in the development of neuropathic sensitisation. We investigated whether restoring descending NAergic tone with intrathecal reboxetine can oppose the development of the neuropathic pain phenotype after tibial nerve transection (TNT). ⋯ In contrast, an equivalent antiallodynic dose of systemic reboxetine (30 mg/kg) was aversive in both naive and TNT rats. On cessation of chronic intrathecal reboxetine, there was a gradual development of allodynic sensitisation that was indistinguishable from control TNT animals by 7 days after the end of dosing. Our results suggest that pharmacological restoration of spinal NAergic tone with intrathecal reboxetine can suppress both allodynia and spontaneous pain in the TNT model.