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

Kaido Kurrikoff, Sulev Kõks, Toshimitsu Matsui, Michel Bourin, Andres Arend, Marina Aunapuu, Eero Vasar

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

Previous studies suggest that cholecystokinin (CCK) is implicated in the modulation of pain sensitivity and the development of neuropathic pain. We used CCK2 receptor deficient (CCK2-/-) 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 CCK2-/- 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 CCK2 receptors, decreased dose-dependently, mechanical sensitivity in wild-type mice. The mechanism of reduced mechanical sensitivity in CCK2-/- mice may be explained by changes in interactions between CCK and opioid systems. Indeed, CCK2-l- mice natively expressed higher levels of lumbar CCK1, opioid δ and κ receptors. Next, we found that CCK2-/- 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 CCK2-l- mice. In addition, induction of neuropathy resulted in further increase of opioid δ receptor in CCK2-/- mice. Gene expression results indicate up-regulation of opioid system in CCK2-/- 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.

Original languageEnglish
Pages (from-to)1577-1586
Number of pages10
JournalEuropean Journal of Neuroscience
Volume20
Issue number6
DOIs
StatePublished - Sep 2004
Externally publishedYes

Keywords

  • CCK
  • CCK knockout mice
  • Gene expression
  • Mechanical sensitivity
  • Neuropathic pain
  • Opioid

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