Is hypovitaminosis D associated with fibromyalgia? A systematic review Yandara A Martins, Camila A E F Cardinali, Maria Ida Ravanelli, Kellen Brunaldi Nutrition Reviews, 2020 Context Recent findings have suggested a high prevalence of vitamin D deficiency or insufficiency in fibromyalgia (FM) patients despite the lack of clinical and pathophysiological evidence. Objective A systematic review was conducted to examine the association between vitamin D status and FM, including the effect of vitamin D supplementation. Data source PubMed, LILACS, Scopus, SciELO, Cochrane, and EMBASE were searched, from January 2000 to July 2018, using the descriptors “Fibromyalgia” and “Vitamin D.” Study selection Trials including FM patients in whom vitamin D levels were assessed were eligible for inclusion. Data extraction Data comprised age, gender, country, aims, bias, diagnosis criteria, cutoff point, and status of vitamin D, together with FM symptoms and vitamin D supplementation protocol. Results A total of 26 articles were selected. Most of the studies were found to present unreliable control groups and small samples. Experimental data on vitamin D supplementation indicated improvement in certain FM symptoms. Conclusion Prevalence of hypovitaminosis D in the FM population and the cause-effect relationship were inconclusive. Nevertheless, vitamin D supplementation may be considered as a co-adjuvant in FM therapy.
Glucocorticoids downregulate systemic nitric oxide synthesis and counteract overexpression of hepatic heme oxygenase-1 during endotoxin tolerance Renato N. Soriano, Maria I. Ravanelli, Marcelo E. Batalhao, Evelin C. Carnio, Luiz G.S. Branco Canadian Journal of Physiology and Pharmacology, 2013 Heme oxygenase (HO)-1 has antioxidant and cytoprotective properties if properly expressed, whereas nitric oxide (NO) impairs tissue perfusion when greatly increased in the blood circulation. Here we hypothesized that the NO and HO-1 systems are altered during lipopolysaccharide (LPS) tolerance, and that glucocorticoids are crucial modulators of systemic NO production and hepatic HO-1 expression during this intriguing phenomenon of cellular reprogramming. Adrenalectomized (ADX) rats with or without administration of dexamethasone (DEX) were challenged with LPS for 3 consecutive days. The plasma levels of corticosterone and nitrate (NOx), and expression of HO-1 protein were assessed. During tolerance, corticosterone levels were elevated, NOx reduced, and HO-1 overexpressed. ADX rats challenged with LPS for 3 consecutive days exhibited a ∼9-fold increase in NOx and a ∼6-fold increase in HO-1, reverted by DEX. Our findings strongly support the fact that glucocorticoids downregulate systemic NO synthesis and counteract hepatic HO-1 overexpression during LPS tolerance.
Plasma corticosterone levels in mouse models of pain M. Benedetti, R. Merino, R. Kusuda, M.I. Ravanelli, F. Cadetti, et al. European Journal of Pain United Kingdom, 2012 BackgroundPain markedly activates the hypothalamic‐pituitary‐adrenal (HPA) axis and increases plasma corticosterone release interfering significantly with nociceptive behaviour as well as the mechanism of action of analgesic drugs.Aims/MethodsIn the present study, we monitored the time course of circulating corticosterone in two mouse strains (C57Bl/6 and Balb/C) under different pain models. In addition, the stress response was investigated following animal handling, intrathecal (i.t.) manipulation and habituation to environmental conditions commonly used in nociceptive experimental assays. We also examined the influence of within‐cage order of testing on plasma corticosterone.ResultsSubcutaneous injection of capsaicin precipitated a prompt stress response whereas carrageenan and complete Freund's adjuvant induced an increased corticosterone release around the third hour post‐injection. However, carrageenan induced a longer increased corticosterone in C57Bl/6 mice. In partial sciatic nerve ligation, neuropathic pain model corticosterone increased only in the first days whereas mechanical hypersensitivity remained much longer. Animal handling also represents an important stressor whereas the i.t. injection per se does not exacerbate the handling‐induced stress response. Moreover, the order of testing animals from the same cage does not interfere with plasma corticosterone levels in the intrathecal procedure. Animal habituation to the testing apparatus also does not reduce the immediate corticosterone increase as compared with non‐habituated mice.ConclusionOur data indicate that HPA axis activation in acute and chronic pain models is time dependent and may be dissociated from evoked hyperalgesia. Therefore, HPA‐axis activation represents an important variable to be considered when designing experimental assays of persistent pain as well as for interpretation of data.
