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Calcium/calmodulin-dependent protein kinase II is involved in the transmission and regulation of nociception in naïve and morphine-tolerant rat nucleus accumbens

  • Kai Wen Xi (Department of Physiology, Faculty of Basic Medical Science, Kunming Medical University) ;
  • De Duo Chen (Department of Physiology, Faculty of Basic Medical Science, Kunming Medical University) ;
  • Xin Geng (Second Department of Neurosurgery, The First Affiliated Hospital, Kunming Medical University) ;
  • Yan Bian (Department of Oncology, The Second Affiliated Hospital, Kunming Medical University) ;
  • Min Xin Wang (Department of Physiology, Faculty of Basic Medical Science, Kunming Medical University) ;
  • Hui Bian (Department of Physiology, Faculty of Basic Medical Science, Kunming Medical University)
  • Received : 2022.11.04
  • Accepted : 2023.02.19
  • Published : 2023.04.01

Abstract

Background: Synaptic plasticity contributes to nociceptive signal transmission and modulation, with calcium/calmodulin-dependent protein kinase II (CaMK II) playing a fundamental role in neural plasticity. This research was conducted to investigate the role of CaMK II in the transmission and regulation of nociceptive information within the nucleus accumbens (NAc) of naïve and morphine-tolerant rats. Methods: Randall Selitto and hot-plate tests were utilized to measure the hindpaw withdrawal latencies (HWLs) in response to noxious mechanical and thermal stimuli. To induce chronic morphine tolerance, rats received intraperitoneal morphine injection twice per day for seven days. CaMK II expression and activity were assessed using western blotting. Results: Intra-NAc microinjection of autocamtide-2-related inhibitory peptide (AIP) induced an increase in HWLs in naïve rats in response to noxious thermal and mechanical stimuli. Moreover, the expression of the phosphorylated CaMK II (p-CaMK II) was significantly decreased as determined by western blotting. Chronic intraperitoneal injection of morphine resulted in significant morphine tolerance in rats on Day 7, and an increase of p-CaMK II expression in NAc in morphine-tolerant rats was observed. Furthermore, intra-NAc administration of AIP elicited significant antinociceptive responses in morphine-tolerant rats. In addition, compared with naïve rats, AIP induced stronger thermal antinociceptive effects of the same dose in rats exhibiting morphine tolerance. Conclusions: This study shows that CaMK II in the NAc is involved in the transmission and regulation of nociception in naïve and morphine-tolerant rats.

Keywords

Acknowledgement

This study was supported by the National Natural Science Foundation of China (No: 81760212).

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