Access the full text.
Sign up today, get DeepDyve free for 14 days.
References for this paper are not available at this time. We will be adding them shortly, thank you for your patience.
Poster-abstracts from SASP 2013 / Scandinavian Journal of Pain 4 (2013) 255–260 259 B6 B7 The mineralocorticoid receptor antagonist Expression of calcium/calmodulin-dependent spironolactone enhances morphine protein kinase II in dorsal root ganglia in antinociception diabetic rats 6 months and 1 year after diabetes induction 1 1 Viljami Jokinen , Tuomas O. Lilius , Mikko S. Neuvonen , L. Ferhatovic, A. Jelicic, M. Boric, A. Banozic, D. 1,3 2,4 Antti J. Väänänen , Mikko O. Niemi , Pekka V. Sapunar, L. Puljak Rauhala , Department of Histology and Embryology, School of 1,5 Eija A. Kalso Medicine, University of Split, Split, Croatia Institute of Biomedicine, Pharmacology, University Aim: The aim of this study was to compare expression of total of Helsinki, Helsinki, Finland calcium/calmodulin-dependent protein kinase II (tCaMKII) and its Institute of Clinical Medicine, Department of , , and isoforms in dorsal root ganglion (DRG) in rat models of Clinical Pharmacology, University of Helsinki, diabetes mellitus type I (DM1), 6 months and 1 year after diabetes Helsinki, Finland induction. Department of Anaesthesia and Intensive Care Methods: A total of 45 male Sprague-Dawley rats weighing Medicine, Helsinki University, Central Hospital, 160–200 g were assigned into four experimental groups: 6-months Helsinki, Finland DM1 and its control group, 1-year and its control group. For the HUSLAB, Helsinki University Central Hospital, induction of DM1, after overnight fasting animals were injected Helsinki, Finland intraperitonealy with 55 mg/kg of the streptozotocine (STZ). Rats Pain Clinic, Department of Anaesthesia and were sacrificed 6 months and 1 year after the diabetes induction. Intensive Care Medicine, Helsinki University Central The L4 and L5 ganglions were removed, fixed, embedded in freezing Hospital, Helsinki, Finland medium and sectioned on a cryostat. Immunofluorescence analy- Aims: Spironolactone, an antimineralocorticoid, has been sis was performed for detection of tCaMKII and its , , and reported to potentiate the cataleptic effect of morphine in the rat. isoforms. Image J software was used for analysis of immunofluo- Since no previous research exists on the matter and the interac- rescence. tion might be clinically significant, the effects of spironolactone on Results: The diabetes was successfully induced as confirmed morphine antinociception and pharmacokinetics in the rat were by measurement of glucose levels and weight increase. Analysis of investigated. tCaMKII expression in DRGs revealed no differences between DM1 Methods: Male SD rats were used to assess the effects and control animals after 6 and 12 months. In diabetic animals, of spironolactone on acute morphine-induced antinociception, the expression of and isoforms decreased significantly after 6 development of morphine tolerance, and established morphine months, compared to the controls, while decrease of and was tolerance in the tail-flick and hot plate tests. Spironolactone was observed after one year of diabetes in diabetic animals. also administered with loperamide to assess whether spirono- Conclusions: The observed changes in the expression of CaMKII lactone enhances the brain distribution of the acknowledged isoforms reveal plastic changes of this enzyme during the chronic P-glycoprotein substrate across the blood–brain barrier. diabetic state and may be involved in the chronic neuropathic pain Results: Spironolactone had no antinociceptive effects of its development. own but when co-administrated with morphine the antinoci- ceptive effect of morphine was greatly enhanced. Morphine http://dx.doi.org/10.1016/j.sjpain.2013.07.014 concentrations in the brain were increased fourfold in the spirono- B8 lactone co-administrated group. Spironolactone did not inhibit the formation of pro-nociceptive morphine-3-glucuronide, nor did Histamine in the locus coeruleus attenuates inhibit the development of tolerance. The peripherally restricted neuropathic hypersensitivity opioid, loperamide, had no antinociceptive effects by itself, but co- administration with spironolactone produced a clear change in the Cong-Yu Jin, Hong Wei, Kaj Karlstedt, Antti hot plate test. Pertovaara Conclusions: Although mineralocorticoids have been proposed Institute of Biomedicine/Physiology, University of to take part in pain signaling, in our setting spironolactone did not Helsinki, Helsinki, Finland have antinociceptive properties of its own. The increased antinoci- ceptive effect of morphine is apparently caused by the increased Aims: Among brain structures receiving efferent projections morphine brain concentrations. We suggest this to be due to P- from the histaminergic tuberomammillary nucleus is the pontine glycoprotein inhibition, as indicated by the loperamide assay. The locus coeruleus (LC), a structure involved in descending noradren- clinical relevance of P-glycoprotein inhibition by spironolactone ergic control of pain. Here we studied whether histamine in the LC is should be studied. involved in descending regulation of neuropathic hypersensitivity. Methods: Peripheral neuropathy was induced by unilateral http://dx.doi.org/10.1016/j.sjpain.2013.07.013 spinal nerve ligation (SNL) in the rat with a chronic intracere- bral and intrathecal catheter for drug administrations. Mechanical hypersensitivity in the injured limb was assessed by monofil- aments. Heat nociception was assessed by determining radiant heat-induced paw flick. Results: Histamine in the LC (ipsilateral to nerve injury) pro- duced a dose-related (1–10g) mechanical antihypersensitivity effect (maximum effect at 15 min and duration of effect 30 min), without influence on heat nociception. Pretreatment of LC with
Scandinavian Journal of Pain – de Gruyter
Published: Oct 1, 2013
You can share this free article with as many people as you like with the url below! We hope you enjoy this feature!
Read and print from thousands of top scholarly journals.
Already have an account? Log in
Bookmark this article. You can see your Bookmarks on your DeepDyve Library.
To save an article, log in first, or sign up for a DeepDyve account if you don’t already have one.
Copy and paste the desired citation format or use the link below to download a file formatted for EndNote
Access the full text.
Sign up today, get DeepDyve free for 14 days.
All DeepDyve websites use cookies to improve your online experience. They were placed on your computer when you launched this website. You can change your cookie settings through your browser.