Pain
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We assessed the effect of back problems on healthcare utilization and costs in a population-based sample of adults from a single-payer health system in Ontario. We conducted a population-based cohort study of Ontario respondents aged ≥18 years of the Canadian Community Health Survey (CCHS) from 2003 to 2012. The CCHS data were individually linked to health administrative data to measure healthcare utilization and costs up to 2018. ⋯ Incremental annual per-person costs were higher in adults with back problems than those without back problems (women: $395, 95% CI $281-$509; men: $196, 95% CI $94-$300). This corresponded to $532 million for women and $227 million for men (adjusted to 2018 Canadian dollars) annually in Ontario given the high prevalence of back problems. Given the high health system burden, new strategies to effectively prevent and treat back problems and thus potentially reduce the long-term costs are warranted.
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Chemotherapy-induced peripheral neuropathy (CIPN) and chemotherapy-induced cognitive impairments (CICI) are common, often severe neurotoxic side effects of cancer treatment that greatly reduce quality of life of cancer patients and survivors. Currently, there are no Food and Drug Administration-approved agents for the prevention or curative treatment of CIPN or CICI. The dual leucine zipper kinase (DLK) is a key mediator of axonal degeneration that is localized to axons and coordinates the neuronal response to injury. ⋯ The protective effects of IACS'8287 are associated with preservation of mitochondrial function in dorsal root ganglion neurons and in brain synaptosomes. In addition, RNA sequencing analysis of dorsal root ganglia reveals modulation of genes involved in neuronal activity and markers for immune cell infiltration by DLK inhibition. These data indicate that CIPN and CICI require DLK signaling in mice, and DLK inhibitors could become an attractive treatment in the clinic when coadministered with cisplatin, and potentially other chemotherapeutic agents, to prevent neurotoxicities as a result of cancer treatment.
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Randomized Controlled Trial
Efficacy and safety of EMA401 in peripheral neuropathic pain: results of two randomised, double-blind, phase 2 studies in patients with postherpetic neuralgia and painful diabetic neuropathy.
The analgesic efficacy and safety of 2 phase 2b studies of EMA401 (a highly selective angiotensin II type 2 receptor antagonist) in patients with postherpetic neuralgia (EMPHENE) and painful diabetic neuropathy (EMPADINE) were reported. These were multicentre, randomised, double-blind treatment studies conducted in participants with postherpetic neuralgia or type I/II diabetes mellitus with painful distal symmetrical sensorimotor neuropathy. Participants were randomised 1:1:1 to either placebo, EMA401 25 mg, or 100 mg twice daily (b.i.d) in the EMPHENE and 1:1 to placebo or EMA401 100 mg b.i.d. in the EMPADINE. ⋯ Out of the planned participants, a total of 129/360 (EMPHENE) and 137/400 (EMPADINE) participants were enrolled. The least square mean reduction in numeric rating scale pain score was numerically in favour of EMA401 100 mg arm in both EMPHENE (treatment difference: -0.5 [95% confidence interval: -1.6 to 0.6; P value: 0.35]) and EMPADINE (treatment difference: -0.6 [95% confidence interval: -1.4 to 0.1; P value: 0.10]) at the end of week 12. However, as the studies were terminated prematurely, no firm conclusion could be drawn but the consistent clinical improvement in pain intensity reduction across these 2 studies in 2 different populations is worth noting.
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Pain education is a popular treatment approach for persistent pain that involves learning a variety of concepts about pain (ie, target concepts), which is thought to be an important part of recovery. Yet, little is known about what patients value learning about pain. A mixed-methods survey was conducted to identify pain concepts that were valued by people with persistent pain who improved after a pain science education intervention. ⋯ I can retrain my overprotective pain system (theme 3) captured the importance of conceptualising pain as a heightened protective response that could be lessened. Responses from close-ended questions confirmed that the target concepts represented by these themes are among those most valued, although divergence with the qualitative data suggests differences between patient and clinician language. These data offer patient-centred conceptualizations and language that could assist in further refining pain education interventions.
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Randomized Controlled Trial
Opening of BKCa channels causes migraine attacks: a new downstream target for the treatment of migraine.
Migraine is a common and frequently disabling neurological disorder, but the initiating migraine mechanisms are still poorly understood. Potassium channel opening may cause migraine, and we therefore examined the migraine-inducing effect of MaxiPost, a large (big)-conductance calcium-activated potassium (BKCa) channel opener, on migraine induction and cephalic vasodilation in individuals with migraine. Twenty-six patients with migraine without aura were randomly allocated to receive an infusion of MaxiPost or placebo on 2 study days separated by at least 1 week. ⋯ The incidence of headache over the 12-hour observation period was higher after MaxiPost day (n = 22) than after placebo (n = 7) (P < 0.0001). We found a significant increase of VMCA and superficial temporal and radial arteries' diameter. Because BKCa channel opening initiates migraine attacks, we suggest that BKCa channel blockers could be potential candidates for novel antimigraine drugs.