Poster-abstracts from SASP 2013 / Scandinavian Journal of Pain 4 (2013) 255–260B6B7The mineralocorticoid receptor antagonistspironolactone enhances morphineantinociceptionExpression of calcium/calmodulin-dependentprotein kinase II in dorsal root ganglia indiabetic rats 6 months and 1 year after diabetesinductionViljami Jokinen 1 , Tuomas O. Lilius 1 , Mikko S.Neuvonen 2 ,Antti J. Väänänen 1,3 , Mikko O. Niemi 2,4 , Pekka V.Rauhala 1 ,Eija A. Kalso 1,5259L. Ferhatovic, A. Jelicic, M. Boric, A. Banozic, D.Sapunar, L. PuljakDepartment of Histology and Embryology, School ofMedicine, University of Split, Split, Croatia1Institute of Biomedicine, Pharmacology, Universityof Helsinki, Helsinki, Finland2 Institute of Clinical Medicine, Department ofClinical Pharmacology, University of Helsinki,Helsinki, Finland3 Department of Anaesthesia and Intensive CareMedicine, Helsinki University, Central Hospital,Helsinki, Finland4 HUSLAB, Helsinki University Central Hospital,Helsinki, Finland5 Pain Clinic, Department of Anaesthesia andIntensive Care Medicine, Helsinki University CentralHospital, Helsinki, FinlandAims: Spironolactone, an antimineralocorticoid, has beenreported to potentiate the cataleptic effect of morphine in the rat.Since no previous research exists on the matter and the interaction might be clinically signiﬁcant, the effects of spironolactone onmorphine antinociception and pharmacokinetics in the rat wereinvestigated.Methods: Male SD rats were used to assess the effectsof spironolactone on acute morphine-induced antinociception,development of morphine tolerance, and established morphinetolerance in the tail-ﬂick and hot plate tests. Spironolactone wasalso administered with loperamide to assess whether spironolactone enhances the brain distribution of the acknowledgedP-glycoprotein substrate across the blood–brain barrier.Results: Spironolactone had no antinociceptive effects of itsown but when co-administrated with morphine the antinociceptive effect of morphine was greatly enhanced. Morphineconcentrations in the brain were increased fourfold in the spironolactone co-administrated group. Spironolactone did not inhibitthe formation of pro-nociceptive morphine-3-glucuronide, nor didinhibit the development of tolerance. The peripherally restrictedopioid, loperamide, had no antinociceptive effects by itself, but coadministration with spironolactone produced a clear change in thehot plate test.Conclusions: Although mineralocorticoids have been proposedto take part in pain signaling, in our setting spironolactone did nothave antinociceptive properties of its own. The increased antinociceptive effect of morphine is apparently caused by the increasedmorphine brain concentrations. We suggest this to be due to Pglycoprotein inhibition, as indicated by the loperamide assay. Theclinical relevance of P-glycoprotein inhibition by spironolactoneshould be studied.http://dx.doi.org/10.1016/j.sjpain.2013.07.013Aim: The aim of this study was to compare expression of totalcalcium/calmodulin-dependent protein kinase II (tCaMKII) and its␣, ␤, ␥ and ␦ isoforms in dorsal root ganglion (DRG) in rat models ofdiabetes mellitus type I (DM1), 6 months and 1 year after diabetesinduction.Methods: A total of 45 male Sprague-Dawley rats weighing160–200 g were assigned into four experimental groups: 6-monthsDM1 and its control group, 1-year and its control group. For theinduction of DM1, after overnight fasting animals were injectedintraperitonealy with 55 mg/kg of the streptozotocine (STZ). Ratswere sacriﬁced 6 months and 1 year after the diabetes induction.The L4 and L5 ganglions were removed, ﬁxed, embedded in freezingmedium and sectioned on a cryostat. Immunoﬂuorescence analysis was performed for detection of tCaMKII and its ␣, ␤, ␥ and ␦isoforms. Image J software was used for analysis of immunoﬂuorescence.Results: The diabetes was successfully induced as conﬁrmedby measurement of glucose levels and weight increase. Analysis oftCaMKII expression in DRGs revealed no differences between DM1and control animals after 6 and 12 months. In diabetic animals,the expression of ␣ and ␤ isoforms decreased signiﬁcantly after 6months, compared to the controls, while decrease of ␥ and ␦ wasobserved after one year of diabetes in diabetic animals.Conclusions: The observed changes in the expression of CaMKIIisoforms reveal plastic changes of this enzyme during the chronicdiabetic state and may be involved in the chronic neuropathic paindevelopment.http://dx.doi.org/10.1016/j.sjpain.2013.07.014B8Histamine in the locus coeruleus attenuatesneuropathic hypersensitivityCong-Yu Jin, Hong Wei, Kaj Karlstedt, AnttiPertovaaraInstitute of Biomedicine/Physiology, University ofHelsinki, Helsinki, FinlandAims: Among brain structures receiving efferent projectionsfrom the histaminergic tuberomammillary nucleus is the pontinelocus coeruleus (LC), a structure involved in descending noradrenergic control of pain. Here we studied whether histamine in the LC isinvolved in descending regulation of neuropathic hypersensitivity.Methods: Peripheral neuropathy was induced by unilateralspinal nerve ligation (SNL) in the rat with a chronic intracerebral and intrathecal catheter for drug administrations. Mechanicalhypersensitivity in the injured limb was assessed by monoﬁlaments. Heat nociception was assessed by determining radiantheat-induced paw ﬂick.Results: Histamine in the LC (ipsilateral to nerve injury) produced a dose-related (1–10 g) mechanical antihypersensitivityeffect (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
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