Rejected

Vestibular evoked myogenic potentials (VEMPs) are a useful and increasingly popular component of the neuro-otology test battery. These otolith-dependent reflexes are produced by stimulating the ears with air-conducted sound or skull vibration and recorded from surface electrodes placed over the neck (cervical VEMPs) and eye muscles (ocular VEMPs). VEMP abnormalities have been reported in various diseases of the ear and vestibular system, and VEMPs have a clear role in the diagnosis of superior semicircular canal dehiscence. However there is significant variability in the methods used to stimulate the otoliths and record the reflexes. This review discusses VEMP methodology and provides a detailed theoretical background for the techniques that are typically used. The review also outlines the common pitfalls in VEMP recording and the clinical applications of VEMPs.

Headache is a common complaint after mild traumatic brain injury (mTBI). Changes in the CNS lipidome were previously associated with acrolein-induced headache in rodents. mTBI caused similar headache-like symptoms in rats; therefore, we tested the hypothesis that mTBI might likewise alter the lipidome. Using a stereotaxic impactor, rats were given either a single mTBI or a series of 4 mTBIs 48 h apart. 72 h later for single mTBI and 7 days later for repeated mTBI, the trigeminal ganglia (TG), trigeminal nucleus (TNC), and cerebellum (CER) were isolated. Using HPLC/MS/MS, ~80 lipids were measured in each tissue and compared to sham controls. mTBI drove widespread alterations in lipid levels. Single mTBI increased arachidonic acid and repeated mTBI increased prostaglandins in all 3 tissue types. mTBI affected multiple TRPV agonists, including N-arachidonoyl ethanolamine (AEA), which increased in the TNC and CER after single mTBI. After repeated mTBI, AEA increased in the TG, but decreased in the TNC. Common to all tissue types in single and repeated mTBI was an increase the AEA metabolite, N-arachidonoyl glycine, a potent activator of microglial migration. Changes in the CNS lipidome associated with mTBI likely play a role in headache and in long-term neurodegenerative effects of repeated mTBI.

Pain experience is a negative complex phenomenon influenced by several mechanisms. Attachment processes may affect the way in which individuals experience and signal pain. Hence, in the last two decades, the role of attachment quality has drawn attention in pain research and practice. However, previous reviews on this topic focused on adulthood and/or specific types or pain. We conducted a narrative review examining the association between attachment and different pain conditions from infancy to adolescence. Two independent researchers searched scientific databases for relevant papers. A total of 17 articles were included. Results highlight the following: (a) children and adolescents with chronic idiopathic pain showed low rates of attachment security compared to control groups; (b) pain conditions are consistently associated with elevated rates of at-risk pattern of attachment and information processing; and (c) the presence of unresolved trauma or loss is higher in children and adolescent who experienced pain compared to healthy controls. Despite the significance of these empirical evidences, the impact of caregiving environment and interpersonal context on pain experience in infancy and preschool age is poorly investigated compared to adulthood. Research on pain and attachment needs to be extended since the majority of the studies are limited to specific pain conditions. Future research should investigate the role of anxious attachment on procedural pain and transition from acute to chronic pain, testing new conceptual models. These findings shed light on the importance of relational factors and psychosocial vulnerabilities in pain clinical practice. An attachment-informed approach to pain will help health professionals to offer adequate support during procedures and to increase effectiveness of interventions. A developmental perspective is needed to integrate familial and relational contribution into a multimodal assessment and treatment of pain. Longitudinal studies are recommended.

This study evaluates oral naproxen and intrauterine instillation of lidocaine for analgesia with intrauterine device (IUD) placement as compared to placebo.

We describe the rational use of enteric coated and unprotected replacement pancreatic enzymes for treatment of malabsorption due to pancreatic insufficiency and for pancreatic pain. Enteric coated formulations mix poorly with food allowing separation of enzymes and nutrients when emptying from the stomach. The site of dissolution of the enteric coating in the intestine is also unpredictable and enzymes may not be released until the distal intestine. Together, these barriers result in the lack of dose-response such that the strategy of increasing the dosage following a suboptimal effect is often ineffective. The ability to maintain the intragastric pH ≥4 with the combination of proton pump inhibitors and antacids suggests that it should be possible to reliably obtain a good response with uncoated enzymes. We also discuss the recognition, treatment and prevention of nutritional deficiencies associated with pancreatic insufficiency and recommend a test and treat strategy to identify and resolve nutritional deficits. Finally, we focus on mechanisms causing pain that may be amenable to therapy with pancreatic enzymes. Pain due to malabsorbed digestive contents can be prevented by successful therapy of malabsorption. Feedback inhibition of endogenous pancreatic secretion can prevent pain associated with pancreatic secretion but requires use of non-enteric coated formulations.

Chronic pain is a highly prevalent problem, involving high costs and seriously affecting a patient's quality of life. This review aimed to systematically review economic evaluations of pharmacological-based treatments for non-malignant chronic pain and to compare different treatment approaches with regard to their economic profile.

Osteoarthritis is one of the most common chronic health conditions associated with pain and disability. Advanced therapies based on mesenchymal stem cells have become valuable options for the treatment of these pathologies. Conditioned serum (CS, "Orthokine") has been used intra-articularly for osteoarthritic patients. In this work, we hypothesized that the rich content on anti-inflammatory proteins and growth factors of CS may exert a beneficial effect on the biological activity of human adipose-derived mesenchymal stem cells (hAdMSCs). studies were designed using hAdMSCs cocultured with CS at different concentrations (2.5, 5, and 10%). Chondrogenic differentiation assays and immunomodulatory experiments using -stimulated lymphocytes were performed. Our results demonstrated that CS significantly enhanced the differentiation of hAdMSCs toward chondrocytes. Moreover, hAdMSCs pre-sensitized with CS reduced the lymphocyte proliferation as well as their differentiation toward activated lymphocytes. These results suggest that coadministration of CS and hAdMSCs may have a beneficial effect on the therapeutic potential of hAdMSCs. Moreover, these results indicate that intra-articular administration of CS might influence the biological behavior of resident stem cells increasing their chondrogenic differentiation and inherent immunomodulatory activity. To our knowledge, this is the first study reporting this combination.

Chronic granulomatous disease (CGD) is a rare primary immunodeficiency disorder caused by a defect in the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex. The disease primarily presents with recurrent infections, and patients may also present with inflammatory conditions, including noninfectious colitis, and an increased frequency of autoimmunity. We report here a patient with CGD in whom the presentation, unlike the classical presentation of CGD, was predominantly of an inflammatory and autoimmune phenotype.

This prospective, randomized and single-blinded study assesses the influence of radial extracorporeal shock wave therapy (rESWT) in patients with low back pain (LBP).

Mirogabalin, a novel ligand for the αδ subunit of voltage-gated calcium channels, has been approved for the treatment of peripheral neuropathic pain including painful diabetic peripheral neuropathy (DPNP) and postherpetic neuralgia (PHN) in Japan. Mirogabalin showed potent and selective binding affinities for the αδ subunits, and slower dissociation rates for the αδ-1 subunit than for the αδ-2 subunit. It also showed potent and long-lasting analgesic effects in rat models of neuropathic pain, and wider safety margins for the central nervous system side effects. A pharmacological study using mutant mice demonstrated that the analgesic effects of mirogabalin were mediated by binding of the drug to the αδ-1 subunit, not the αδ-2 subunit. The pharmacological properties of mirogabalin can be associated with its unique binding characteristics. The bioavailability of mirogabalin is high and its plasma exposure increases dose-proportionally. Mirogabalin is mainly excreted via the kidneys in an unchanged form, thus, mirogabalin has a low possibility of undergoing drug-drug interaction, while dose adjustment based on the creatinine clearance level is specified in patients with renal impairment. In double-blind, placebo-controlled phase 3 studies in Asian patients with DPNP and PHN, mirogabalin showed significant and dose-dependent pain relief, and all tested doses of mirogabalin were well tolerated. In summary, mirogabalin has a balanced efficacy versus safety profile, and can provide an alternative therapeutic option for the treatment of peripheral neuropathic pain.