Accepted

To determine if the ages at pubertal milestones are associated with the prevalence of adolescent migraine.

Sphingolipids are crucial molecules of the mammalian epidermis. The formation of skin-specific ceramides contributes to the formation of lipid lamellae, which are important for the protection of the epidermis from excessive water loss and protect the skin from the invasion of pathogens and the penetration of xenobiotics. In addition to being structural constituents of the epidermal layer, sphingolipids are also key signaling molecules that participate in the regulation of epidermal cells and the immune cells of the skin. While the importance of ceramides with regard to the proliferation and differentiation of skin cells has been known for a long time, it has emerged in recent years that the sphingolipid sphingosine 1-phosphate (S1P) is also involved in processes such as the proliferation and differentiation of keratinocytes. In addition, the immunomodulatory role of this sphingolipid species is becoming increasingly apparent. This is significant as S1P mediates a variety of its actions via G-protein coupled receptors. It is, therefore, not surprising that dysregulation in the signaling pathways of S1P is involved in the pathophysiological conditions of skin diseases. In the present review, the importance of S1P in skin cells, as well as the immune cells of the skin, is elaborated. In particular, the role of the molecule in inflammatory skin diseases will be discussed. This is important because interfering with S1P signaling pathways may represent an innovative option for the treatment of inflammatory skin diseases.

Opioid drugs have analgesic properties used to treat chronic and post-surgical pain due to descending pain modulation. The use of opioids is often associated with adverse effects or clinical issues. This study aimed to evaluate the toxicity of opioids by exposing the neuroblastoma cell line (SH-SY5Y) to 0, 1, 10, and 100 µM oxycodone and naloxone for 24 h. Analyses were carried out to evaluate cell cytotoxicity, identification of cell death, DNA damage, superoxide dismutase (SOD), glutathione S-transferase (GST), and acetylcholinesterase (AChE) activities, in addition to molecular docking. Oxycodone and naloxone exposure did not alter the SH-SY5Y cell viability. The exposure to 100 µM oxycodone and naloxone significantly increased the cells' DNA damage score compared to the control group. Naloxone exposure significantly inhibited AChE, GST, and SOD activities, while oxycodone did not alter these enzymes' activities. Molecular docking showed that naloxone and oxycodone interact with different amino acids in the studied enzymes, which may explain the differences in enzymatic inhibition. Naloxone altered the antioxidant defenses of SH-SY5Y cells, which may have caused DNA damage 24 h after the exposure. On the other hand, more studies are necessary to explain how oxycodone causes DNA damage.

Fibromyalgia syndrome (FMS) is a chronic musculoskeletal disorder of unknown etiology that affects up to 5.0% of the world population. It has a high female predominance, between 80 and 96%. Due to the low number of diagnosed men, research work has focused mainly on women. The extensive body of literature on sex differences in pain in the general population suggests that men and women differ in their responses to pain, with greater sensitivity to pain and a higher risk of clinical pain commonly observed among women. This review aims to: (1) determine how pain is assessed or what types of questionnaires are used, (2) examine whether there are differences in pain characteristics between men and women with FMS and (3) describe how pain is conceptualized or manifested in patients at a qualitative level. In this study, the scoping review method of articles published in the last 5 years (2016-2022) was used. Ten articles were included. The most used questionnaires and scales to assess pain were the PVAS (Pain Visual Analogue Scale) and the FIQ (Fibromyalgia Impact Questionnaire). On the other hand, five categories were obtained: (1) qualities of pain, (2) uncertainty and chaos, (3) pain as an aggravating factor, (4) adaptation to the new reality and (5) the communication of pain. It has been observed that both subjective perception and widespread pain are higher in women. Men, on the other hand, have a worse impact of the pathology, more painful experiences and more catastrophic thoughts about pain. An updated knowledge of pain in FMS and whether it differs according to sex would be beneficial for clinicians to make an earlier diagnosis and treatment and, in turn, benefit patients suffering from this chronic disease.

Previously, a new dichotomous outcome was developed, calculated as 55% reduction in the International Hidradenitis Suppurativa 4 score (IHS4-55). It was validated in datasets of adalimumab and placebo treated HS patients. External validation is an important aspect of clinical outcomes.

Drugs enhancing the availability of noradrenaline are gaining prominence in the therapy of chronic neuropathic pain. However, underlying mechanisms are not well understood, and research has thus far focused on α2-adrenergic receptors and neuronal excitability. Adrenergic receptors are also expressed on glial cells, but their roles toward antinociception are not well deciphered. This study addresses the contribution of β2-adrenergic receptors (β2-ARs) to the therapeutic modulation of neuropathic pain in mice. We report that selective activation of β2-ARs with Formoterol inhibits pro-inflammatory signaling in microglia ex vivo and nerve injury-induced structural remodeling and functional activation of microglia in vivo. Systemic delivery of Formoterol inhibits behaviors related to neuropathic pain, such as mechanical hypersensitivity, cold allodynia as well as the aversive component of pain, and reverses chronically established neuropathic pain. Using conditional gene targeting for microglia-specific deletion of β2-ARs, we demonstrate that the anti-allodynic effects of Formoterol are primarily mediated by microglia. Although Formoterol also reduces astrogliosis at late stages of neuropathic pain, these functions are unrelated to β2-AR signaling in microglia. Our results underline the value of developing microglial β2-AR agonists for relief from neuropathic pain and clarify mechanistic underpinnings.

Most studies on interstitial cystitis/bladder pain syndrome and chronic prostatitis/chronic pelvic pain syndrome use typical or average levels of pelvic pain or urologic symptom intensity as their outcome, as both are associated with reduced quality of life (QOL). Symptom exacerbations or "flares" have also been found to be associated with reduced QOL, but no studies, to our knowledge, have investigated whether these associations are independent of typical pelvic pain levels and thus might be useful additional outcome measures (or stated differently, whether reducing flare frequency even without reducing mean pain intensity may be important to patients).

Chronic pain and ADHD are common conditions among youth that negatively impact functioning. This review fills a critical gap by summarizing current research on chronic pain and ADHD comorbidity, and it proposes a conceptual model of shared associations and underlying mechanisms. The aims of the current study were to: (1) review the extant literature and present estimates of the prevalence of comorbid non-headache chronic pain and ADHD in youth and (2) describe potential shared mechanisms for ADHD and chronic non-headache pain in youth. We also outline future directions to inform future research and interventions directed to youth with comorbid pain and ADHD. A scoping review of the literature was performed in MEDLINE, PsycInfo, and Cochrane Database of Systematic Reviews using a wide range of search terms related to pain, Attention Deficit-Hyperactivity Disorder, childhood, adolescence, and young adulthood. Eleven published studies were included in the review. These studies examined the prevalence of chronic pain among youth with ADHD, the prevalence of ADHD in chronic pain samples, and the association between chronic pain and ADHD among youth. Findings revealed results from studies indicating a higher prevalence of ADHD among youth with chronic pain and a higher prevalence of chronic pain in samples of youth with ADHD. Findings from this scoping review suggest an association between chronic pain and ADHD among youth. Little research was found to examine the etiology of this association. Future studies should examine underlying mechanisms of comorbid chronic pain and ADHD.