YokoCo

Hypothalamus is a key region in migraine attacks. In addition, women are disproportionately affected by migraine. The calcitonin gene-related peptide (CGRP) system is an important key player in migraine pathophysiology. CGRP signaling could be a target of hormones that influence migraine. Our aim is to identify the expression of vasopressin and its receptors in the brain and in the trigeminovascular system with focus on the migraine-related regions and, furthermore, to examine the role of sex on the expression of neurohormones in the trigeminal ganglion.

Although dimethyl fumarate (DMF) has been approved since 2017 for treatment of moderate-to-severe plaque psoriasis, limited data on its safety and efficacy are available in clinical practice. The objective was to assess the efficacy and safety of DMF in patients with moderate-to-severe plaque psoriasis through 52 weeks in conditions close to real clinical practice.

Psoriasis is an inflammatory skin condition that can negatively affect numerous domains for quality of life, including sexual function. We aimed to systematically compare sexual function between women with and without psoriasis through meta-analysis. Databases were searched for studies assessing sexual function in women with and without psoriasis using the Female Sexual Function Index (FSFI). Meta-analyses were conducted in R (v4.1.2) to determine: (i) the odds ratio (OR) of sexual dysfunction and (ii) the mean difference (MD) for FSFI scores and sub-scores. Eight studies (five case-control, three cross-sectional) were eligible for review, encompassing 563 women with psoriasis and 525 controls. Risk of bias for included studies was considered as low to moderate. Psoriasis was associated with greater odds of female sexual dysfunction (OR 2.67, 95% CI 1.93,3.69; p < 0.0001). Compared to controls, women with psoriasis had significantly lower mean scores for desire (p < 0.0001), arousal (p = 0.002), lubrication (p = 0.003), orgasm (p < 0.0001), satisfaction (p < 0.0001) and total scores (p < 0.0001). Mean pain scores did not significantly differ between psoriasis patients and controls (p = 0.051). We identified significantly impaired sexual function in women with psoriasis compared to controls, suggesting that routine assessment of sexual health may be beneficial. Prospective studies of larger sample size are required in order to explore the underlying mechanisms and risk factors.

Approximately 10% of patients who undergo inguinal hernia repair or Pfannenstiel incision develop chronic (> three months) postsurgical inguinal pain (PSIP). If medication or peripheral nerve blocks fail, a neurectomy is the treatment of choice. However, some patients do not respond to this treatment. In such cases, stimulation of the dorsal root ganglion (DRG) appears to significantly reduce chronic PSIP in selected patients.

Calcitonin gene-related peptide (CGRP) is a neuropeptide with diverse physiological functions. Its two isoforms (α and β) are widely expressed throughout the body in sensory neurons, as well as in other cell types, such as motor neurons and neuroendocrine cells. CGRP acts via at least two G protein-coupled receptors that form unusual complexes with receptor activity-modifying proteins. These are the CGRP receptor and the AMY receptor; in rodents, additional receptors come into play. Although CGRP is known to produce many effects, the precise molecular identity of the receptor(s) that mediate CGRP effects is seldom clear. Despite the many enigmas still in CGRP biology, therapeutics that target the CGRP axis to treat or prevent migraine are a bench to bedside success story. This review provides a contextual background on the regulation and sites of CGRP expression and CGRP receptor pharmacology. The physiological actions of CGRP in the nervous system are discussed, along with updates on CGRP actions in the cardiovascular, pulmonary, gastrointestinal, immune, hematopoietic, and reproductive systems, and metabolic effects of CGRP in muscle and adipose tissues. We cover how CGRP in these systems is associated with disease states, most notably migraine. In this context, we discuss how CGRP actions in both the peripheral and central nervous systems provide a basis for therapeutic targeting of CGRP in migraine. Finally, we highlight potentially fertile ground for the development of additional therapeutics and combinatorial strategies that could be designed to modulate CGRP signaling for migraine and other diseases.

Chronic-pain is a debilitating illness that has become exceedingly widespread with currently limited treatments. Differences in the molecular signature of nociceptors, have been demonstrated between human and the commonly-used mouse model, suggesting functional differences in detection and transmission of noxious-stimuli. Therefore, direct understanding of pain-physiology in humans is required for pain treatment. This could be facilitated by studying humans carrying deleterious genetic mutations affecting pain sensation. The transient receptor potential vanilloid 1 (TRPV1) channel is associated with several body-functions, in particular, noxious-heat detection and inflammatory-pain. Reports of adverse effects in human trials have hinder the clinical development of TRPV1 antagonists as novel pain relievers. Hence, studies on the functional roles of TRPV1, which currently rely mainly on evidences obtained from rodents, should be extended to humans. Here, we examined humans carrying a unique missense mutation in TRPV1, rendering the channel non-functional. The affected individual demonstrated lack of aversion towards capsaicin and elevated heat-pain threshold. Surprisingly, he showed elevated cold-pain threshold and extensive neurogenic inflammatory flare and pain-responses following application of the TRPA1 channel-activator, mustard-oil. Our study provides the first direct evidence for pain-related functional-changes linked to TRPV1 in humans, which is a prime target in the development of novel pain-relievers.

Spinal cord stimulator (SCS) is approved to treat various pain conditions and is commonly seen in the chronic pain patient population. Due to the nature of the device and its location, infections associated with SCS have a particularly high morbidity. According to post-market data and medical device reports, 87% of patients receiving SCS implants were given perioperative antibiotics as the implantable neurostimulator or receiver pocket serve as the most common sites of infection. The most common antibiotics for surgical prophylaxis given are first-generation cephalosporins (cefalexin, cefazolin) at the time of implantation. If deep infection is suspected, imaging in the form of CT scan should be obtained as physical exam is not always sufficient. For infections involving the epidural space, vertebra, or intervertebral discs, MRI is the preferred imaging modality. If meningitis is suspected, a lumbar puncture is recommended. Positive cultures can help guide antibiotic therapy.

The main objective of this study is to examine chronic pain and limping in relation to lower extremity and pelvic fracture location in addition to fracture combinations if multiple fractures are present on the same leg that have not been previously reported. We hypothesize that fracture pattern and location of lower extremity and pelvis fractures of multiple injured patients influence their long-term pain outcome.

Psoriasis is a chronic, immune-mediated, skin disease with a significantly negative impact on patients' quality of life. Moderate-to-severe disease often requires systemic therapies and currently available ones still have numerous disadvantages or limitations. Tyrosine kinase 2 (TYK2) mediates immune signaling of IL-12, IL-23, and type I interferons, without interfering with other critical systemic functions. This article aims to review the current knowledge on deucravacitinib, a new oral drug which selectively inhibits TYK2, granting it a low risk of off-target effects. Two phase 3, 52-week trials evaluated deucravacitinib 6 mg against placebo and apremilast – POETYK PSO-1 and PSO-2 -, enrolling 1688 patients with moderate-to-severe psoriasis. At week 16, over 50% of patients treated with deucravacitinib reached PASI75, significantly superior to placebo and apremilast. Symptomatic improvement was also reported, with greater impact on itch. Deucravacitinib was well tolerated and safe. There were no reports of serious infections, thromboembolic events, or laboratory abnormalities. Persistent efficacy and consistent safety profiles were reported for up to 2 years. Deucravacitinib has the potential to become a safe, effective, and well-tolerated treatment for patients with moderate-to-severe disease. Future studies will be important to determine the exact role of this drug in the treatment of psoriasis.