Accepted

α-Conotoxins (α-CTxs) can selectively target nicotinic acetylcholine receptors (nAChRs) and are important drug leads for the treatment of cancer, chronic pain, and neuralgia. Here, we chemically synthesized a formerly defined rat α7 nAChR targeting α-CTx Mr1.1 and evaluated its activity at human nAChRs. Mr1.1 was most potent at the human (h) α9α10 nAChR with a half-maximal inhibitory concentration (IC) of 92.0 nM. Molecular dynamic simulations suggested that Mr1.1 favorably binds at the α10(+)α9(-) and α9(+)α9(-) sites via hydrogen bonds and salt bridges, stabilizing the channel in a closed conformation. Although Mr1.1 and another antagonist, α-CTx Vc1.1 share high sequence similarity and disulfide-bond framework, Mr1.1 has distinct orientations at hα9α10. Based on the Mr1.1-hα9α10 model, analogues were generated, and the more potent Mr1.1[S4Dap], antagonized hα9α10 with an IC of 4.0 nM. Furthermore, Mr1.1[S4Dap] displayed analgesic activity in the rat chronic constriction injury (CCI) pain model and therefore presents a promising drug candidate.

Recent evidence has shown that vestibular migraine is strongly associated with cognitive difficulties. However, limited data exist on real-world effects of that dysfunction. The objective of this study is to understand the epidemiology of cognitive dysfunction with vestibular migraine and associated sequelae using National Health Interview Survey data.

Pain Catastrophizing Scale (PCS) is the most used scale to measure pain catastrophizing. In breast cancer survivors (BCS), pain catastrophizing is related to upper-limbs dysfunction and disability. This study aimed to assess the internal consistency, internal structure and convergent validity of the Spanish version of the PCS in Spanish BCS MATERIAL AND METHODS: BCS were recruited from the service of Medical Oncology of the University Clinical Hospital Virgen de la Victoria, in Málaga (Spain). The psychometric properties were evaluated with analyses factor structure by maximum likelihood extraction (MLE), internal consistency, and construct validity by confirmatory factor analysis (CFA).

Transcutaneous electrical nerve stimulation (TENS) is a non-pharmacological intervention used in the treatment of acute and chronic pain conditions. The first clinical studies on TENS were published over 50 years ago, when effective parameters of stimulation were unclear and clinical trial design was in its infancy. Over the last two decades, a better understanding of the mechanisms underlying TENS efficacy has led to the development of an adequate dose and has improved outcome measure utilization. The continued uncertainty about the clinical efficacy of TENS to alleviate pain, despite years of research, is related to the quality of the clinical trials included in systematic reviews. This summary of the evidence includes only trials with pain as the primary outcome. The outcomes will be rated as positive (+), negative (-), undecided (U), or equivalent to other effective interventions (=). In comparison with our 2014 review, there appears to be improvement in adverse events and parameter reporting. Importantly, stimulation intensity has been documented as critical to therapeutic success. Examinations of the outcomes beyond resting pain, analgesic tolerance, and identification of TENS responders remain less studied areas of research. This literature review supports the conclusion that TENS may have efficacy for a variety of acute and chronic pain conditions, although the magnitude of the effect remains uncertain due to the low quality of existing literature. In order to provide information to individuals with pain and to clinicians treating those with pain, we suggest that resources for research should target larger, high-quality clinical trials including an adequate TENS dose and adequate timing of the outcome and should monitor risks of bias. Systematic reviews and meta-analyses should focus only on areas with sufficiently strong clinical trials that will result in adequate sample size.

The prevalence of pregnant people with opioid use disorder (OUD), including those receiving medications for opioid use disorder (MOUD), is increasing. Challenges associated with pain management in people with OUD include tolerance, opioid-induced hyperalgesia, and risk for return to use. Yet, there are few evidence-based recommendations for pain management in the setting of pregnancy and the postpartum period, and many peripartum pain management studies exclude people with OUD. This scoping review summarized the available literature on peridelivery pain management in people with OUD, methodologies used, and identified specific areas of knowledge gaps. PubMed and Embase were comprehensively searched for publications in all languages on peripartum pain management among people with OUD, both treated with MOUD and untreated. Potential articles were screened by title, abstract, and full text. Data abstracted were descriptively analyzed to map available evidence and identify areas of limited or no evidence. A total of 994 publications were imported for screening on title, abstracts, and full text, yielding 84 publications identified for full review: 32 (38.1%) review articles, 14 (16.7%) retrospective studies, and 8 (9.5%) case reports. There were 5 randomized controlled trials. Most studies (64%) were published in perinatology (32; 38.1%) journals or anesthesiology (22; 26.2%) journals. Specific areas lacking trial or systematic review evidence include: (1) methods to optimize psychological and psychosocial comorbidities relevant to acute pain management around delivery; (2) alternative nonopioid and nonpharmacologic analgesia methods; (3) whether or not to use opioids for severe breakthrough pain and how best to prescribe and monitor its use after discharge; (4) monitoring for respiratory depression and sedation with coadministration of other analgesics; (5) optimal neuraxial analgesia dosing and adjuncts; and (6) benefits of abdominal wall blocks after cesarean delivery. No publications discussed naloxone coprescribing in the labor and delivery setting. We observed an increasing number of publications on peripartum pain management in pregnant people with OUD. However, existing published works are low on the pyramid of evidence (reviews, opinions, and retrospective studies), with a paucity of original research articles (<6%). Opinions are conflicting on the utility and disutility of various analgesic interventions. Studies generating high-quality evidence on this topic are needed to inform care for pregnant people with OUD. Specific research areas are identified, including utility and disutility of short-term opioid use for postpartum pain management, role of continuous wound infiltration and truncal nerve blocks, nonpharmacologic analgesia options, and the best methods to support psychosocial aspects of pain management.

Fibromyalgia (FM) is a chronic pain condition often accompanied by sleep problems and depression that are each associated with reduced physical ability including postural control. Research supports a sequential association between pain intensity and depression in FM, and poor sleep quality may play a key role in this relationship. This study aimed to verify a serial pattern of associations among sleep quality, pain intensity, and depressive symptoms and quantify these effects on objective postural control.

Quality of life (QoL) and sleep, which are essential for well-being in the mental, physical, and socioeconomic domains, are impaired in psoriatic patients. However, the exact role of the clinical subtype of psoriasis in this aspect remains poorly studied.

Prurigo nodularis (PN), characterised by inevitable chronicity and severe pruritus, is most frequently associated with atopy compared to other origins. However, the skin transcriptomic profiling of PN arising from atopic dermatitis (AD), so-called atopic PN (APN), remains unclear. We sought to explore the cutaneous transcriptome of APN with severe pruritus and compare it to classic AD. RNA sequencing was performed on the lesional skin from 13 APN and 11 AD patients with severe pruritus (itch numerical rating scale score ≥7) and normal skin from 11 healthy subjects. Quantitative real-time polymerase chain reaction and immunochemistry were used for validation. We detected 1085 and 1984 differentially expressed genes (DEGs) in lesional APN skin and lesional AD skin versus normal skin, respectively. In total, 142 itch/inflammation-related DEGs were identified. Itch/inflammation-related DEGs, such as IL-6, IL-10, IL-13, oncostatin M, and IL-4 receptor, had elevated gene transcript levels in both diseases. The itch/inflammation-related DEGs that increased only in APN were mainly neuroactive molecules, while many inflammatory mediators such as T helper 22-related genes were found to be increased only in AD. Both disorders showed mixed Th1/Th2/Th17 polarisation and impaired skin barrier. In contrast to AD, M1/M2 macrophage activation, tumour necrosis factor production, fibrosis, revascularization and neural dysregulation are unique features of APN. The study findings broaden our understanding of the pathogenesis underlying APN, which provides insights into novel pathogenesis with potential therapeutic implications.