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Prevalence of functional somatic syndromes (FSS) in the general population varies with observed overlap between syndromes. However, studies including a range of FSS are sparse. We investigated prevalence and characteristics of various FSS and the unifying diagnostic construct bodily distress syndrome (BDS), and identified mutual overlap of the FSS and their overlap with BDS. We included a stratified subsample of 1590 adults from a randomly selected Danish general population sample (n = 7493). Telephonic diagnostic interviews performed by three trained physicians were used to identify individuals with FSS and BDS. Prevalence of overall FSS was 9.3%; 3.8% for irritable bowel, 2.2% for chronic widespread pain, 6.1% for chronic fatigue, 1.5% for whiplash associated disorders, and 0.9% for multiple chemical sensitivity. Prevalence of BDS was 10.7% where 2.0% had the multi-organ type. FSS were highly overlapping with low likelihood of having a "pure" type. Diagnostic agreement of FSS and BDS was 92.0%. Multi-syndromatic FSS and multi-organ BDS were associated with female sex, poor health, physical limitations, and comorbidity. FSS are highly prevalent and overlapping, and multi-syndromatic cases are most affected. BDS captured the majority of FSS and may improve clinical management, making the distinction between multi- and mono-syndromatic patients easier.
Learn More >Migraine is recognized as the second leading cause of disability globally. Lasmiditan is a novel, selective serotonin 5-HT receptor agonist developed for acute treatment of migraine. Here we analyzed effects of lasmiditan on migraine disability assessed with the Migraine Disability Assessment (MIDAS) scale for interim data from a long-term safety study.
Learn More >Pituitary adenylate cyclase-activating polypeptide-38 (PACAP38) induces headache in healthy volunteers but the precise mechanisms by which PACAP38 leads to headache are unclear. We investigated the headache preventive effect of sumatriptan and ketorolac on PACAP38-induced headache in healthy volunteers. In addition, we explored contribution of vascular mechanisms to PACAP38-induced headache using high resolution magnetic resonance angiography.
Learn More >Burning mouth syndrome (BMS) is a neuropathic pain disorder associated with a burning sensation on oral mucosal surfaces with frequently reported xerostomia, dysgeusia and tingling or paraesthetic sensations. However, patients present no clinically evident causative lesions. The poor classification of the disorder has resulted in a diagnostic challenge, particularly for the clinician/dentist evaluating these individuals. Major research developments have been made in the BMS field in recent years to address this concern, principally in terms of the pathophysiological mechanisms underlying the disorder, in addition to therapeutic advancements. For the purpose of this review, an update on the pathophysiological mechanisms will be discussed from a neuropathic, immunological, hormonal and psychological perspective. This review will also focus on the many therapeutic strategies that have been explored for BMS, including antidepressants/antipsychotics, nonsteroidal anti-inflammatories, hormone replacement therapies, phytotherapeutic compounds and non-pharmacological interventions, overall highlighting the lack of controlled clinical studies to support the effectiveness of such therapeutic avenues. Particular focus is given to the cannabinoid system, and the potential of cannabis-based therapeutics in managing BMS patients.
Learn More >Behavioral alterations, like mechanical and thermal hyperalgesia, and modulation of biomarkers in the peripheral and central nervous systems (CNS) are markers of chronic pain. Transcranial direct current stimulation (tDCS) with exercise is a promising therapy for pain due to its neuromodulatory capacity.
Learn More >Total knee arthroplasty (TKA) is considered an effective treatment for pain relief and improved physical performances in end-stage knee osteoarthritis. However, several studies have reported less favorable outcomes after TKA with chronic pain rates of approximately 20%. Exercise might be an effective treatment strategy for chronic pain following TKA, but no randomized controlled trials have evaluated its effect. Therefore, the purpose of this randomized controlled trial is to investigate whether a 12-week neuromuscular exercise (NEuroMuscular EXercise training program for patients with knee or hip osteoarthritis assigned for total joint replacement; NEMEX-TJR) program combined with pain neuroscience education (PNE) provides greater pain relief and improvement in physical performances than PNE alone at 12 months follow-up in a population of patients with chronic pain after primary TKA.
Learn More >Mindfulness-based interventions have been receiving growing attention in cancer care.
Learn More >No adequate treatment is available for painful urinary bladder disorders such as interstitial cystitis/bladder pain syndrome, and the identification of new urological therapeutic targets is an unmet need. The sigma-1 receptor (σ-R) modulates somatic pain, but its role in painful urological disorders is unexplored. The urothelium expresses many receptors typical of primary sensory neurons (e.g. TRPV1, TRPA1 and P2 × 3) and high levels of σ-R have been found in these neurons; we therefore hypothesized that σ-R may also be expressed in the urothelium and may have functional relevance in this tissue. With western blotting and immunohistochemical methods, we detected σ-R in the urinary bladder in wild-type (WT) but not in σ-R-knockout (σ-KO) mice. Interestingly, σ-R was located in the bladder urothelium not only in mouse, but also in human bladder sections. The severity of histopathological (edema, hemorrhage and urothelial desquamation) and biochemical alterations (enhanced myeloperoxidase activity and phosphorylation of extracellular regulated kinases 1/2 [pERK1/2]) that characterize cyclophosphamide-induced cystitis was lower in σ-KO than in WT mice. Moreover, cyclophosphamide-induced pain behaviors and referred mechanical hyperalgesia were dose-dependently reduced by σ-R antagonists (BD-1063, NE-100 and S1RA) in WT but not in σ1-KO mice. In contrast, the analgesic effect of morphine was greater in σ-KO than in WT mice. Together these findings suggest that σ-R plays a functional role in the mechanisms underlying cyclophosphamide-induced cystitis, and modulates morphine analgesia against urological pain. Therefore, σ-R may represent a new drug target for urinary bladder disorders.
Learn More >Despite the growing knowledge of the mechanisms of chronic pain, the treatment of this disorder in the clinic remains a major challenge. Src-family protein tyrosine kinases (SFKs), a group of non-receptor protein tyrosine kinases, have been implicated in neuronal development and synaptic plasticity. SFKs are critical for the regulate of N-methyl-D-aspartic acid receptor (NMDAR) 2B subunit phosphorylation by various transmembrane receptors, e.g., G-protein coupled receptors (GPCRs), EphB receptors (EphBRs), increased intracellular calcium, epidermal growth factor (EGF) and other growth factors, and thus contribute to the development of chronic pain. SFKs have also been regarded as important points of convergence of intracellular signalling components for the regulation of microglial functions and the immune response. Additionally, the intrathecal administration of SFK inhibitors significantly alleviates mechanical allodynia in different chronic pain models. Here, we reviewed the current evidence for the role of SFKs in the development of chronic pain caused by complete Freund's adjuvant (CFA) injection, peripheral nerve injury (PNI), streptozotocin (STZ) injection and bone metastasis. Moreover, the role of SFKs in the development of morphine tolerance is also discussed. The regulation of SFKs therefore has emerged as a potential therapeutic target for the treatment of chronic pain in terms of safety and efficacy.
Learn More >The trigeminal ganglion with its three trigeminal nerve tracts consists mainly of clusters of sensory neurons with their peripheral and central processes. Most neurons are surrounded by satellite glial cells and the axons are wrapped by myelinating and non-myelinating Schwann cells. Trigeminal neurons express various neuropeptides, most notably, calcitonin gene-related peptide (CGRP), substance P, and pituitary adenylate cyclase-activating polypeptide (PACAP). Two types of CGRP receptors are expressed in neurons and satellite glia. A variety of other signal molecules like ATP, nitric oxide, cytokines, and neurotrophic factors are released from trigeminal ganglion neurons and signal to neighboring neurons or satellite glial cells, which can signal back to neurons with same or other mediators. This potential cross-talk of signals involves intracellular mechanisms, including gene expression, that can modulate mediators of sensory information, such as neuropeptides, receptors, and neurotrophic factors. From the ganglia cell bodies, which are outside the blood-brain barrier, the mediators are further distributed to peripheral sites and/or to the spinal trigeminal nucleus in the brainstem, where they can affect neural transmission. A major question is how the sensory neurons in the trigeminal ganglion differ from those in the dorsal root ganglion. Despite their functional overlap, there are distinct differences in their ontogeny, gene expression, signaling pathways, and responses to anti-migraine drugs. Consequently, drugs that modulate cross-talk in the trigeminal ganglion can modulate both peripheral and central sensitization, which may potentially be distinct from sensitization mediated in the dorsal root ganglion.
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