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

K. Kurrikoff; S. Kõks; T. Matsui; M. Bourin; A. Arend; M. Aunapuu; E. Vasar

doi:10.1111/j.1460-9568.2004.03619.x

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

Journal article

Peer reviewed

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

K. Kurrikoff, S. Kõks, T. Matsui, M. Bourin, A. Arend, M. Aunapuu and E. Vasar

European Journal of Neuroscience, Vol.20(6), pp.1577-1586

2004

DOI: https://doi.org/10.1111/j.1460-9568.2004.03619.x

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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) (-/-) mice. In addition, induction of neuropathy resulted in further increase of opioid delta receptor in CCK(2) (-/-) mice. Gene expression results indicate up-regulation of opioid system in CCK(2) (-/-) mice, which apparently result in decreased neuropathy score. Our study suggests that not only pain sensitivity, but also mechanical sensitivity and the development of neuropathic pain are regulated by antagonistic interactions between CCK and opioid systems.

Details

Title: Deletion of the CCK2 receptor gene reduces mechanical sensitivity and abolishes the development of hyperalgesia in mononeuropathic mice
Authors/Creators: K. Kurrikoff (Author/Creator) - University of Tartu
S. Kõks (Author/Creator) - University of Tartu
T. Matsui (Author/Creator) - Kobe University
M. Bourin (Author/Creator) - Nantes Université
A. Arend (Author/Creator) - University of Tartu
M. Aunapuu (Author/Creator) - University of Tartu
E. Vasar (Author/Creator) - University of Tartu
Publication Details: European Journal of Neuroscience, Vol.20(6), pp.1577-1586
Publisher: Wiley
Identifiers: 991005542207107891
Murdoch Affiliation: Murdoch University
Language: English
Resource Type: Journal article

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Collaboration types: Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.195 Neuroendocrine & Intestinal Disorders; 1.195.1096 Gastrin/CCK Functions
Web Of Science research areas: Neurosciences
ESI research areas: Neuroscience & Behavior