Investigation of Lake Hévíz Mineral Water Balneotherapy and Hévíz Mud Treatment in Murine Osteoarthritis and Rheumatoid Arthritis Models.

Arthritic diseases are the most frequent causes of chronic pain and disability. Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovial inflammation and progressive structural joint damage. Osteoarthritis is a degenerative process of the articular cartilage associated with hypertrophic changes in the bone. The aim of the present study was to investigate the anti-inflammatory and analgesic effects of Hévíz thermal water and mud in monosodium iodoacetate- (MIA-) (25 mg/ml, 20 µl i.a.) induced osteoarthritis and Complete Freund's adjuvant- (CFA-) (1 mg/ml, 50-50 µl s.c) induced rheumatoid arthritis murine models. The mechanonociceptive threshold of female NMRI mice (n=6- 8 mice/ group) was measured by aesthesiometry, and paw volume was monitored with plethysmometry, knee joint diameter with digital micrometer, and dynamic weight bearing on the hind limbs with a Bioseb instrument. Periarticular bone destruction was assessed by SkyScan 1176 in vivo micro-CT. Inflammatory cytokines were detected by ELISA in plasma samples. Treatments (30 min, every working day) with tap water, sand, and a combined therapy of tap water and sand served as controls. Hévíz medicinal water and combined treatment with water and mud significantly decreased the mechanical hyperalgesia and knee oedema in MIA-induced osteoarthritis model. However, balneotherapy did not influence mechanical hyperalgesia, weight bearing, or oedema formation induced by CFA. Neither medicinal water nor mud treatment ameliorated deep structural damage of the bones or the joints in the animal models. On the basis of the present findings, we conclude that balneotherapy is an effective complementary treatment to reduce the pain sensation and swelling in degenerative joint diseases such as osteoarthritis. Our experimental data are in agreement with the previous human studies that also confirmed antinociceptive and anti-inflammatory effects of thermal water and Hévíz mud treatments.

Upregulation of extraneuronal TRPV1 expression in chronic rhinosinusitis with nasal polyps.

BACKGROUND: Chronic rhinosinusitis (CRS) is a multifactorial upper airway disease with unclear etiology. Neuronal Transient Receptor Potential Vanilloid 1 (TRPV1) and Ankyrin 1 (TRPA1) channels have been implicated in the pathogenesis of CRS. We aimed to detect the expression of extraneuronal TRPV1 and TRPA1 receptors in nasal polyp (NP) tissue samples. METHODOLOGY: Samples were obtained from fourty-two CRS pateints with nasal polyp and sixteen healthy controls to measure receptor gene expression by quantitative PCR, protein localization by immunohistochemistry and cytokine profile by multiplex bead immunoassay. RESULTS: Non-neuronal TRPV1, TRPA1 receptors were expressed in biopsy samples of NP. A population of mast cells and macrophages were immunopositive for TRPV1 and TRPA1. A fraction of plasma cells expressed TRPV1 but not TRPA1 and neither receptor was present on eosinophils. The local gene expression of extraneuronal TRPV1, TRPA1 receptors was also proven. TRPV1 mRNA levels were significantly increased in CRSwNP patients with asthma and allergic rhinitis compared to their NP counterparts. CONCLUSIONS: Elevated TRPV1 levels in comorbid asthma and allergy may have a function in CRSwNP. Subpopulation-specific TRPV1 presence on plasma and mast cells can indicate delicate roles in regulating activation and release of inflammatory mediators.

Marijuana smoke induces severe pulmonary hyperresponsiveness, inflammation, and emphysema in a predictive mouse model not via CB1 receptor activation.

Sporadic clinical reports suggested that marijuana smoking induces spontaneous pneumothorax, but no animal models were available to validate these observations and to study the underlying mechanisms. Therefore, we performed a systematic study in CD1 mice as a predictive animal model and assessed the pathophysiological alterations in response to 4-mo-long whole body marijuana smoke with integrative methodologies in comparison with tobacco smoke. Bronchial responsiveness was measured with unrestrained whole body plethysmography, cell profile in the bronchoalveolar lavage fluid with flow cytometry, myeloperoxidase activity with spectrophotometry, inflammatory cytokines with ELISA, and histopathological alterations with light microscopy. Daily marijuana inhalation evoked severe bronchial hyperreactivity after a week. Characteristic perivascular/peribronchial edema, atelectasis, apical emphysema, and neutrophil and macrophage infiltration developed after 1 mo of marijuana smoking; lymphocyte accumulation after 2 mo; macrophage-like giant cells, irregular or destroyed bronchial mucosa, goblet cell hyperplasia after 3 mo; and severe atelectasis, emphysema, obstructed or damaged bronchioles, and endothelial proliferation at 4 mo. Myeloperoxidase activity, inflammatory cell, and cytokine profile correlated with these changes. Airway hyperresponsiveness and inflammation were not altered in mice lacking the CB1 cannabinoid receptor. In comparison, tobacco smoke induced hyperresponsiveness after 2 mo and significantly later caused inflammatory cell infiltration/activation with only mild emphysema. We provide the first systematic and comparative experimental evidence that marijuana causes severe airway hyperresponsiveness, inflammation, tissue destruction, and emphysema, which are not mediated by the CB1 receptor.

TRPA1 receptor is upregulated in human oral lichen planus.

OBJECTIVE: Oral lichen planus (OLP) is a chronic inflammatory disease of unknown etiology with antigen-specific and non-specific mechanisms. Transient receptor potential ankyrin 1 (TRPA1) is a non-selective cation channel activated by noxious stimuli such as oxidative stress products evoking pain and release of proinflammatory mediators from sensory nerve endings culminating in neurogenic inflammation. Extraneuronal TRPA1s, for example, on immune cells possess yet unknown functions. SUBJECTS AND METHODS: We studied the buccal mRNA expression (qPCR) and protein localization (immunohistochemistry) of TRPA1 receptors and key OLP mediator transcripts in oral mucosa samples of healthy volunteers (n = 9), OLP patients (n = 43), and OLP-like hyperkeratotic patients (n = 12). RESULTS: We measured 27.7- and 25.5-fold TRPA1 mRNA increase in OLP and OLP-like hyperkeratotic patients compared to healthy controls. TRPA1 transcripts elevated 2.4-fold in hypertensive OLP but not in hyperkeratotic patients compared to counterparts, reduced by 1.6-fold by angiotensin-convertase inhibitor intake. TRPA1 messenger RNA was more coexpressed with transcripts of tumor necrosis factor α than with interferon γ. Keratinocytes, macrophages but not T cells expressed TRPA1. CONCLUSIONS: We provided evidence for the extraneuronal presence and upregulation of the proinflammatory TRPA1 receptor in buccal samples of patients with OLP. This may implicate the ion channel in the pathomechanism of OLP.

Topical acetone treatment induces neurogenic oedema on the sensitized mouse ear: an in vivo study using transient receptor potential vanilloid 1 (TRPV1) receptor knockout mice.

OBJECTIVE: The participation of sensory neurons and transient receptor potential vanilloid 1 (TRPV1) receptors in phorbol 12-myristate 13-acetate (PMA)-induced nerve-sensitizing effect was examined. MATERIALS AND METHODS: PMA dissolved in acetone and acetone were applied to the ears of TRPV1 receptor knockout and wild-type mice. Different groups of animals received ibuprofen, anti-interleukin-1 beta (IL-1beta) antibody, resiniferatoxin (RTX) or capsaicin pretreatment. Ear thickness, myeloperoxidase activity and IL-1beta content of the ears were determined. Histological evaluation was performed. RESULTS: PMA exerted potentiating action on contralateral acetone-induced ear oedema, which was inhibited by ibuprofen, topical capsaicin desensitization of the acetone-treated ear as well as by systemic RTX pretreatment. Neither the lack of TRPV1 receptors nor anti-IL-1beta antibody prevented sensitizing effect. CONCLUSIONS: The TRPV1 receptor-independent potentiating action of PMA on contralateral acetone-induced ear oedema is mediated via capsaicin-sensitive afferents and prostanoids are involved. IL-1beta is not essential in this process.