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The proper identification of chronic migraine is one of the mainstays for general practitioners. This study therefore aims to assess the epidemiology and determinants of chronic migraine in primary care in Italy by testing five operational case definition algorithms.
Learn More >Prospective cohort study OBJECTIVE.: The aims of this study were to evaluate the outcome of surgical as well as non-surgical treatment for patients with lumbar herniated disc (LHD) or lumbar spinal stenosis (LSS) after two years and to identify predictors for non-success.
Learn More >The present study characterized the behavioral pharmacology of a novel, mixed-action delta-selective (78:1) opioid receptor agonist, BBI-11008. This glycopeptide drug candidate was tested in assays assessing antinociception (acute, inflammatory, and neuropathic pain-like conditions) and side-effect endpoints (respiratory depression and drug self-administration).
Learn More >Herpetic neuralgia is a painful condition following herpes zoster disease, which results from Varicella-zoster virus reactivation in the dorsal or trigeminal sensory ganglia. Nevertheless, the pathophysiological mechanisms involved in herpetic neuralgia are not well understood. Recently, we identified, that neuroimmune-glia interactions in the sensory ganglion is a critical mechanism for the development of herpetic neuralgia. Here, we investigate the contribution of S100A9, a well-known pro-inflammatory molecule produced by myeloid cells, for the development of herpetic neuralgia using a murine model of HSV-1 infection. We found that cutaneous HSV-1 infection results in an increase of S100A9 expression in the Dorsal Root Ganglia (DRGs). Infiltrating neutrophils into the DRGs were the main source of S100A9 post HSV-1 infection. Functionally, genetic or pharmacological inhibition of S100A9 impairs the development of HSV-1 infection-induced mechanical pain hypersensitivity. Finally, we found that the pronociceptive role of S100A9 in herpetic neuralgia depends on the TLR4/TNF pathway. These results unraveled previously unknown mechanisms involved in the pathophysiology of herpetic neuralgia and indicate that S100A9 might be an important target for novel therapies aiming acute herpetic neuralgia.
Learn More >While persistent opioid use after surgery has been the subject of a large number of studies, it is unknown how much variability in the definition of persistent use impacts the reported incidence across studies. The objective was to evaluate the incidence of persistent use estimated with different definitions using a single cohort of postoperative patients, as well as the ability of each definition to identify patients with opioid-related adverse events.
Learn More >The ATP1A2 coding α2 subunit of Na,K-ATPase, which is predominantly located in astrocytes, is a causative gene of familial hemiplegic migraine type 2 (FHM2). FHM2 model mice (Atp1a2 ) are susceptible to cortical spreading depression (CSD), which is profoundly related to migraine aura and headache. However, astrocytic properties during CSD have not been examined in FHM2 model mice. Using Atp1a2 crossed with transgenic mice expressing G-CaMP7 in cortical neurons and astrocytes (Atp1a2 ), we analyzed the changes in Ca concentrations during CSD. The propagation speed of Ca waves and the percentages of astrocytes with elevated Ca concentrations in Atp1a2 were higher than those in wild-type mice. Increased percentages of astrocytes with elevated Ca concentrations in Atp1a2 may contribute to FHM2 pathophysiology.
Learn More >The objective of this study is to investigate the association of clinical markers of obesity and weight trajectories with chronic musculoskeletal pain (CMP). This is a cross-sectional study using baseline data from ELSA-Brasil MSK cohort. CMP was evaluated at nine body sites (neck, shoulders, upper back, elbows, lower back, wrists/hands, hips/thighs, knees, ankles/feet), and defined as pain lasting > 6 months in the past year. General and abdominal obesity levels were classified according to accepted cut-offs for body mass index (BMI), waist circumference (WC) and waist-height ratio (WHtR). Binomial and multinomial logistic regressions tested for associations with CMP at any site, at ≥ 3 sites (multisite) and in upper + lower limbs + axial skeleton (generalized). A total of 2899 participants (mean age 56.0 ± 8.93) were included, 55.0% reported CMP, 19.1% had multisite, and 10.3% had generalized CMP. After adjustments for sex, age, education, physical activity and depressive symptoms, nearly all the investigated markers of obesity were associated with any CMP, multisite and generalized CMP, with strongest associations being observed for general obesity level II/III: OR 2.08 (95% CI 1.45-2.99), OR 3.19 (95% CI 2.06-4.94) and OR 3.65 (2.18-6.11), respectively. Having excess weight currently or both at age 20 and currently was also associated with all CMP presentations. Associations of greater magnitude were consistently observed at higher obesity levels and longer exposures to excess weight (dose-response). These results may support the contribution of obesity-derived mechanical and inflammatory mechanisms of CMP, and indicate a role for the accumulation of exposure to excess weight across the adult life course.
Learn More >TRPM8 is the main ion channel responsible for cold transduction in the somatosensory system. Nerve terminal availability of TRPM8 determines cold sensitivity, but how axonal secretory organelles control channel delivery remains poorly understood. Here we examine the distribution of TRPM8 and trafficking organelles in cold-sensitive peripheral axons and disrupt trafficking by targeting the ARF-GEF GBF1 pharmacologically or the small GTPase RAB6 by optogenetics. In axons of the sciatic nerve, inhibition of GBF1 interrupts TRPM8 trafficking and increases association with the trans-Golgi network, LAMP1, and Golgi satellites, which distribute profusely along the axonal shaft. Accordingly, both TRPM8-dependent ongoing activity and cold-evoked responses reversibly decline upon GBF1 inhibition in nerve endings of corneal cold thermoreceptors. Inhibition of RAB6, which also associates to Golgi satellites, decreases cold-induced responses in vivo. Our results support a non-conventional axonal trafficking mechanism controlling the availability of TRPM8 in axons and cold sensitivity in the peripheral nervous system.
Learn More >High-resolution structures of TRPV channels: unveiling a functionally diverse group of ion channels.
Transient receptor potential vanilloid (TRPV) channels are part of the superfamily of TRP ion channels and play important roles in widespread physiological processes including both neuronal and non-neuronal pathways. Various diseases such as skeletal abnormalities, chronic pain, and cancer are associated with dysfunction of a TRPV channel. In order to obtain full understanding of disease pathogenesis and create opportunities for therapeutic intervention, it is essential to unravel how these channels function at a molecular level. In the past decade, incredible progress has been made in biochemical sample preparation of large membrane proteins and structural biology techniques, including cryo-electron microscopy. This has resulted in high resolution structures of all TRPV channels, which has provided novel insights into the molecular mechanisms of channel gating and regulation that will be summarized in this review. This article is protected by copyright. All rights reserved.
Learn More >Despite evidence of the analgesic benefits of cannabis, there remains a relative scarcity of research on the short- and long-term effects of cannabis use in individuals with chronic pain.
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