Expression of calcium/calmodulin-dependent protein kinase II in dorsal root ganglia in diabetic rats 6 months and 1 year after diabetes induction

Expression of calcium/calmodulin-dependent protein kinase II in dorsal root ganglia in diabetic... 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 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Scandinavian Journal of Pain de Gruyter

Expression of calcium/calmodulin-dependent protein kinase II in dorsal root ganglia in diabetic rats 6 months and 1 year after diabetes induction

Free
1 page

Loading next page...
1 Page
 
/lp/degruyter/expression-of-calcium-calmodulin-dependent-protein-kinase-ii-in-dorsal-kCwSc5LpTm
Publisher
De Gruyter
Copyright
© 2013 Scandinavian Association for the Study of Pain
ISSN
1877-8860
eISSN
1877-8879
D.O.I.
10.1016/j.sjpain.2013.07.014
Publisher site
See Article on Publisher Site

Abstract

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

Journal

Scandinavian Journal of Painde Gruyter

Published: Oct 1, 2013

There are no references for this article.

You’re reading a free preview. Subscribe to read the entire article.


DeepDyve is your
personal research library

It’s your single place to instantly
discover and read the research
that matters to you.

Enjoy affordable access to
over 18 million articles from more than
15,000 peer-reviewed journals.

All for just $49/month

Explore the DeepDyve Library

Search

Query the DeepDyve database, plus search all of PubMed and Google Scholar seamlessly

Organize

Save any article or search result from DeepDyve, PubMed, and Google Scholar... all in one place.

Access

Get unlimited, online access to over 18 million full-text articles from more than 15,000 scientific journals.

Your journals are on DeepDyve

Read from thousands of the leading scholarly journals from SpringerNature, Elsevier, Wiley-Blackwell, Oxford University Press and more.

All the latest content is available, no embargo periods.

See the journals in your area

DeepDyve

Freelancer

DeepDyve

Pro

Price

FREE

$49/month
$360/year

Save searches from
Google Scholar,
PubMed

Create lists to
organize your research

Export lists, citations

Read DeepDyve articles

Abstract access only

Unlimited access to over
18 million full-text articles

Print

20 pages / month

PDF Discount

20% off