Deletion of the CCK2 receptor gene reduces mechanical sensitivity and abolishes the development of hyperalgesia in mononeuropathic mice

The European Journal of Neuroscience
K KurrikoffE Vasar

Abstract

Previous studies suggest that cholecystokinin (CCK) is implicated in the modulation of pain sensitivity and the development of neuropathic pain. We used CCK(2) receptor deficient (CCK(2) (-/-)) mice and assessed their mechanical sensitivity using Von Frey filaments, as well as the development and time course of mechanical hyperalgesia in a model of neuropathic pain. We found that CCK(2) (-/-) mice displayed mechanical hyposensitivity, which was reversed to the level of wild-type animals after administration of naloxone (0.1-10 mg/kg). On the other hand, injection of L-365260 (0.01-1 mg/kg), an antagonist of CCK(2) receptors, decreased dose-dependently, mechanical sensitivity in wild-type mice. The mechanism of reduced mechanical sensitivity in CCK(2) (-/-) mice may be explained by changes in interactions between CCK and opioid systems. Indeed, CCK(2) (-/-) mice natively expressed higher levels of lumbar CCK(1), opioid delta and kappa receptors. Next, we found that CCK(2) (-/-) mice did not develop mechanical hyperalgesia in the Bennett's neuropathic pain model. Induction of neuropathy resulted in decrease of lumbar pro-opiomelanocortin (POMC) gene expression in wild-type mice, but increase of POMC expression in CCK(2) (-/-) mic...Continue Reading

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Citations

Aug 23, 2008·Transgenic Research·Marina AunapuuAndres Arend
Dec 31, 2008·Journal of Medicinal Chemistry·Yaguo ZhengPhilip S Portoghese
Mar 3, 2007·Genes, Brain, and Behavior·L C SchalkwykS Kõks
Oct 5, 2010·Behavioural Brain Research·Jürgen InnosEero Vasar
Jun 11, 2008·Behavioural Brain Research·Urho AbramovEero Vasar
Dec 7, 2007·Behavioural Brain Research·Sulev KõksLeonard C Schalkwyk
Jul 22, 2009·Neuroscience Letters·Junesun KimYoung Wook Yoon
Apr 17, 2008·The European Journal of Neuroscience·Kaido KurrikoffEero Vasar
Jul 11, 2006·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·Kristiina RootsMihkel Zilmer
Jul 26, 2005·Peptides·Richard J Bodnar, Gad E Klein
Feb 22, 2011·Pharmacology, Biochemistry, and Behavior·Mónica Ambriz-TututiVinicio Granados-Soto
Jul 11, 2014·Progress in Neurobiology·Elaine M JenningsDavid P Finn
Dec 1, 2020·Frontiers in Pharmacology·Takafumi HayashiShinobu Sakurada

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