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This study was performed to evaluate trends in and provide future direction for anesthesiology education, research, and clinical practice.

Bone metastases frequently occur in patients with cancer. Skeletal-related events (SREs), including pain, impaired mobility, hypercalcemia, pathological fracture, spinal cord and nerve root compression, and bone marrow infiltration, can decrease the quality of life of the patients and increase the risk of morbidity. The mechanism of pain due to bone metastasis is complicated and involves various interactions among tumor cells, bone cells, activated inflammatory cells, and bone-innervating neurons. Cancer pain due to bone metastasis can be crippling and a chronic state that causes sarcopenia. For pain management, it is important to diagnose whether the pain is based on background pain or breakthrough pain due to bone metastasis. In addition, the management goal of cancer pain due to bone metastasis is not only to achieve pain relief but also to prevent pain progression and SREs. Pain mechanisms should be applied to achieve optimal management. This review aims to discuss the mechanisms of cancer pain due to bone metastasis and review the recommended drug therapies.

Painful peripheral neuropathy is a common neurological complication associated with human immunodeficiency virus (HIV) infection and anti-retroviral therapy. We characterized the impact of two CB2 cannabinoid agonists (AM1710 and LY2828360 – ligands differing in signaling bias and CNS penetration) on neuropathic nociception induced by the antiretroviral agent Zalcitabine (2'-3'-dideoxycitidine; ddC). We also used a conditional knockout approach to identify cell types mediating CB2 agonist-induced antinociceptive efficacy and sparing of morphine tolerance. AM1710 and LY2828360 alleviated ddC-induced neuropathic nociception in mice of both sexes. These benefits were absent in global CB2 knockout mice, which exhibited robust morphine antinociception. Like morphine, AM1710 blunted ddC-induced increases in proinflammatory cytokine (IL-1β, TNF-α) and chemokine (CCL2) mRNA expression levels. We generated advillin;CB2 conditional knockout mice to ascertain the role of CB2 localized to primary sensory neurons in CB2-mediated therapeutic effects. Antinociceptive efficacy of both AM1710 and LY2828360, but not reference analgesics, were absent in advillin;CB2 mice, which exhibited robust ddC-induced neuropathy. In ddC-treated CB2 mice, LY2828360 suppressed development of morphine tolerance and reversed established morphine tolerance, albeit with greater efficacy in male compared to female mice. LY2828360 failed to block or reverse morphine tolerance in advillin;CB2 mice. The present studies indicate that CB2 activation may alleviate HIV-associated antiretroviral neuropathy and identify a previously unreported mechanism through which CB2 activation produces antinociceptive efficacy. Our results also provide the first evidence that a CB2 agonist can reverse established morphine tolerance and demonstrate that CB2 localized to peripheral sensory neurons mediates the opioid tolerance sparing efficacy of CB2 agonists.

Optical control of G protein-coupled receptor (GPCR) signaling is a highly valuable approach for comprehensive understanding of GPCR-based physiologies and controlling them precisely. However, optogenetics for GPCR signaling is still developing and requires effective and versatile tools with performance evaluation from their molecular properties. Here, we systematically investigated performance of two bistable opsins that activate Gi/Go-type G protein (mosquito Opn3 (MosOpn3) and lamprey parapinopsin (LamPP)) in optical control in vivo using . Transgenic worms expressing MosOpn3, which binds 13- retinal to form photopigments, in nociceptor neurons showed light-induced avoidance responses in the presence of all- retinal, a retinal isomer ubiquitously present in every tissue, like microbial rhodopsins and unlike canonical vertebrate opsins. Remarkably, transgenic worms expressing MosOpn3 were ~7,000 times more sensitive to light than transgenic worms expressing ChR2 in this light-induced behavior, demonstrating the advantage of MosOpn3 as a light switch. LamPP is a UV-sensitive bistable opsin having complete photoregenerative ability by green light. Accordingly, transgenic worms expressing LamPP in cholinergic motor neurons stopped moving upon violet light illumination and restored coordinate movement upon green light illumination, demonstrating color-dependent control of behavior using LamPP. Furthermore, we applied molecular engineering to produce MosOpn3-based tools enabling light-dependent upregulation of cAMP or Ca levels and LamPP-based tool enabling clamping cAMP levels color dependently and context independently, extending their usability. These findings define the capacity of two bistable opsins with similar retinal requirement as ChR2, providing numerous strategies for optical control of various GPCR-based physiologies as well as GPCR signaling itself.

Numerous medications are used for the preventive treatment of chronic migraine (CM), including oral treatments, onabotulinumtoxinA (onabotA; BOTOX), and calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs). Despite substantial clinical trial evidence, less is published about the real-world experience of these treatments based on data routinely collected from a variety of sources. This systematic review assessed real-world evidence on the effectiveness and safety of preventive treatments for CM in adults.

The objectives of this study were to (1) report long-term health-related quality of life (HRQoL) outcomes among patients using rimegepant preventatively in BHV3000-305 (NCT03732638) open-label extension (OLE) and (2) map Migraine-Specific Quality of Life questionnaire version 2.1 (MSQv2) to EQ-5D-3L utility values over the double-blind treatment (DBT; 0-12 weeks) and the OLE (13-64 weeks) to assess the influence of treatment on these values.

: The relationship between migraine and tension-type headache (TTH) with Parkinson's disease (PD) is controversial, while a common pathophysiological link remains obscure. The aim of this systematic review is to investigate the association between PD, migraine and TTH. : Following PRISMA, we searched MEDLINE, WebofScience, Scopus, CINAHL, Cochrane Library and ClinicalTrials.gov up to 1 July 2022 for observational studies examining the prevalence and/or associations of PD with migraine and TTH. We pooled proportions, standardized mean differences (SMD) and odds ratios (OR) with random effects models. The risk of bias was assessed with the Newcastle-Ottawa scale (PROSPERO CRD42021273238). : Out of 1031 screened studies, 12 were finally included in our review (median quality score 6/9). The prevalence of any headache among PD patients was estimated at 49.1% (760 PD patients; 95% CI 24.8-73.6), migraine prevalence at 17.2% (1242 PD patients; 95% CI 9.9-25.9), while 61.5% (316 PD patients; 95% CI 52.6-70.1) of PD patients with migraine reported headache improvement after PD onset. Overall, migraine was not associated with PD (302,165 individuals; OR = 1.11; 95% CI 0.72-1.72).However, cohort studies demonstrated a positive association of PD among lifetime migraineurs (143,583 individuals; OR = 1.54, 95% CI 1.28-1.84), while studies on 12-month migraine prevalence yielded an inverse association (5195 individuals; OR = 0.64, 95% CI 0.43-0.97). Similar findings were reported by 3 studies with data on the TTH-PD relationship (high prevalence, positive association when examined prospectively and an inverse relationship on 12-month prevalence). These data were not quantitatively synthesized due to methodological differences among the studies. Finally, PD patients suffering from any headache had a lower motor unified Parkinson's disease rating scale (UPDRS) score (503 PD patients; SMD -0.39; 95% CI -0.57 to -0.21) compared to PD patients not reporting headache. There is an unclear association of headaches in genetic PD cohorts. : Observational data suggest that migraine and TTH could be linked to PD, but the current literature is conflicting.

Sural nerve neuroma is often caused by an injury during prior surgery, for example, osteosynthesis or ligament refixations at ankle level. Different surgical techniques to treat neuroma have been described. Neurectomy of an injured symptomatic sural nerve has been described as a treatment option for neuropathic pain. The aim of this study was to evaluate the outcomes of this technique to operatively treat sural nerve neuroma in our department.

Netherton syndrome (NS) is a rare disorder of cornification associated with high morbidity. It is caused by bi-allelic mutations in SPINK5 encoding the serine protease inhibitor LEKTI. Previous studies have shown Th17 skewing with IL-23 upregulation in NS, raising the possibility that targeting these inflammatory pathways may alleviate disease manifestations. We ascertained the therapeutic efficacy of six doses of ustekinumab administered to three patients with NS over a period of 13 months using the Ichthyosis Area and Severity Index (IASI), the Dermatology Life Quality Index (DLQI), a visual analogue scale (VAS) for itch and the peak-pruritus numeric rating scale (PP-NRS). Histopathology analysis including CD3, CD4, CD8 and interleukin 17 (IL-17) immunostaining, was performed at baseline and 4 weeks following the last ustekinumab dose. Total IASI scores were reduced by 28% in two patients at week 16 with sustained response by week 56. No consistent improvement in DLQI, VAS for itch and PP-NRS scores was observed. The inflammatory infiltrate and the degree of acanthosis were slightly reduced at week 56 as compared to baseline. No significant change in immunostaining of the various inflammatory markers was observed at week 56. In conclusion, this case series did not demonstrate a significant therapeutic effect of ustekinumab in NS.