Pain
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Inhibition of voltage-gated calcium (CaV) channels is a potential therapy for many neurological diseases including chronic pain. Neuronal CaV1/CaV2 channels are composed of α, β, γ and α2δ subunits. The β subunits of CaV channels are cytoplasmic proteins that increase the surface expression of the pore-forming α subunit of CaV. ⋯ IPPQ was antinociceptive in naive animals and reversed allodynia and hyperalgesia in models of acute (postsurgical) and neuropathic (spinal nerve ligation, chemotherapy- and gp120-induced peripheral neuropathy, and genome-edited neuropathy) pain. IPPQ did not cause akinesia or motor impairment, a common adverse effect of CaV2.2 targeting drugs, when injected into the brain. IPPQ, a quinazoline analog, represents a novel class of CaV2.2-targeting compounds that may serve as probes to interrogate CaVα-CaVβ function and ultimately be developed as a nonopioid therapeutic for chronic pain.
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Although several studies have found that chronic pain is characterized by increased cross-network connectivity between salience network, sensorimotor network, and default mode network (DMN), a large sample-size investigation allowing for a more reliable evaluation of somatotopic specificity and subgroup analyses with linkage to clinical pain intensity has been lacking. We enrolled healthy adults and a large cohort of patients (N = 181) suffering from chronic low back pain (cLBP). To specifically link brain connectivity with clinical pain intensity, patients were scanned at baseline and after performing physical maneuvers that exacerbated pain. ⋯ Hence, increased information transfer between salience processing regions, particularly anterior insula, and DMN may be strongly influenced by pain catastrophizing. Increased information transfer between the salience network and S1 likely plays an important role in shifting nociceptive afference away from self-referential processing, reallocating attentional focus, and affective coding of nociceptive afference from specific body areas. These results demonstrate S1 somatotopic specificity for cross-network connectivity in encoding clinical back pain and moderating influence of catastrophizing for DMN/insula connectivity.
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Chronic pain affects 1 in 5 people and has been shown to disrupt attention. Here, we investigated whether pain disrupts everyday decision making. In study 1, 1322 participants completed 2 tasks online: a shopping-decisions task and a measure of decision outcomes over the previous 10 years. ⋯ In study 2, 44 healthy participants completed the shopping-decisions task with and without experimentally induced pain. Participants made more errors while in pain than while pain-free. We suggest that the disruptive effect of pain on attending translates into poorer decisions in more complex and ecologically valid contexts, that the effect is causal, and that the consequences are not only attentional but also financial.
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Clinicians report reluctance to deliver opioid-tapering advice to patients with chronic pain, in part due to concerns that patients will be angry and dissatisfied. An experiment was conducted to examine chronic pain patients' emotional and attitudinal responses to simulated opioid-tapering advice. Patients scheduled for an initial assessment at a tertiary pain clinic and currently taking opioid medications for pain (N = 196) were randomly assigned to view video footage of a standardized patient receiving 1 of 3 forms of treatment advice: (1) stay on current medication (2) change to a different pain medication, or (3) taper off pain medications and participate in a CBT-based pain self-management program. ⋯ Furthermore, participants' responses to simulated opioid-tapering and opioid-change advice were not significantly different, suggesting that participants responded positively to the prospect of change in treatment strategy. Additional analyses revealed that participants with a longer history of chronic pain and opioid use responded less positively to simulated opioid-tapering advice. The results of this study contribute to our understanding of factors that may shape chronic pain patients' responses to opioid-tapering advice and suggest that patients may respond more positively to opioid-tapering advice if it is presented together with an alternative treatment approach.