Pain
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Brainstem areas involved in descending pain modulation are crucial for the analgesic actions of opioids. However, the role of opioids in these areas during tolerance, opioid-induced hyperalgesia (OIH), and in chronic pain settings remains underappreciated. We conducted a revision of the recent studies performed in the main brainstem areas devoted to descending pain modulation with a special focus on the medullary dorsal reticular nucleus (DRt), as a distinctive pain facilitatory area and a key player in the diffuse noxious inhibitory control paradigm. ⋯ However, the upregulation of MOR and DOR, at the rostral ventromedial medulla, in inflammatory pain models, suggests therapeutic avenues to explore. Mechanistically, the rationale for the diversity and complexity of alterations in the brainstem is likely provided by the alternative splicing of opioid receptors and the heteromerization of MOR. In conclusion, this review emphasizes how important it is to consider the effects of opioids at these circuits when using opioids for the treatment of chronic pain and for the development of safer and effective opioids.
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Randomized Controlled Trial
Randomized, double-blind, controlled trial of a combination of alpha-lipoic acid and pregabalin for neuropathic pain: the PAIN-CARE trial.
We compared a combination of the nonsedating antioxidant, alpha-lipoic acid (ALA), with the sedating anticonvulsant, pregabalin, vs each monotherapy to treat neuropathic pain due to peripheral neuropathies. In this randomized, double-blind, 3-period crossover trial, participants received oral ALA, pregabalin, and their combination-each for 6 weeks. The primary outcome was mean daily pain intensity at maximal tolerated doses (MTD); secondary outcomes included quality of life (SF-36), sleep (Medical Outcomes Study-Sleep Scale), adverse effects, drug doses, and other measures. ⋯ SF-36 total scores (higher number indicates better quality of life) were 66.6 (1.88), 70.1 (1.88), and 69.4 (1.87) with ALA, pregabalin, and combination ( P < 0.05 for ALA vs combination and pregabalin). At MTD, there were no statistically significant treatment differences in adverse effects or drug doses. This trial demonstrates superiority of pregabalin vs ALA but provides no evidence to suggest added benefit of combining ALA with pregabalin to treat neuropathic pain.
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Randomized Controlled Trial
Placebo analgesia and nocebo hyperalgesia in patients with Alzheimer disease and healthy participants.
The role of placebo analgesia and nocebo hyperalgesia in patients with Alzheimer disease (AD) is largely unknown, with only few studies in the area. Therefore, this study aims to investigate to which extent placebo analgesia and nocebo hyperalgesia effects are present in patients experiencing mild-to-moderate AD. Twenty-one patients with AD (test population) and 26 healthy participants (HP; design validation) were exposed to thermal pain stimulation on 3 test days: Lidocaine condition (open/hidden lidocaine administration), capsaicin condition (open/hidden capsaicin administration), and natural history (no treatment), in a randomized, within-subject design. ⋯ With a well-controlled experimental setting, this study suggests that patients with AD may not experience placebo analgesia effects. Nocebo hyperalgesia effects in patients with AD needs further research. These findings may have implications for the conduction of clinical trials and the treatment of patients with AD in clinical practice.
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Studies from multiple countries report that most hospitalized children, especially the youngest and sickest, experience pain that is often severe yet inadequately treated. Evidence suggests this can lead to immediate and lifelong consequences affecting children, families, and communities. Partnership and shared decision-making by children, families, and clinicians is the ideal pediatric healthcare model and can improve care quality and safety, including pain care. ⋯ The authors applied a reflexive content analysis to the data and developed 3 broad categories: (1) connecting and sharing knowledge about pain, (2) user-centred designs, and (3) preserving roles. These findings outlined caregiver and youth recommendations for portal configurations that deeply engage and empower children and families in pain care through multidirectional knowledge sharing, supporting caregiver and clinicians' roles without burdening, or replacing human interaction implicit in family-centered pain care. Further research should measure the impact of portals on pain-related outcomes and explore the perspectives of clinicians.