Pain MechanismResearch PaperInflammation-induced increase in hyperpolarization-activated, cyclic nucleotide-gated channel protein in trigeminal ganglion neurons and the effect of buprenorphine
Section snippets
Animals
Experiments were conducted on 40 male Sprague–Dawley rats of 60–150 g and 3–5 weeks of age from the Anatomy and Cell Biology colony at the University of Melbourne. All procedures were approved by the University of Melbourne Animal Experimentation Ethics Committee and comply with the guidelines of the Committee for Research and Ethical Issues of IASP (Zimmermann, 1983). Every effort was made to minimize the number of animals used and their suffering.
Retrograde tracing and induction of inflammation
Animals were anesthetized with a mixture of
HCN channel protein in trigeminal ganglion neurons
The presence of HCN isoforms 1 and 2 was determined in trigeminal ganglia using Western blot analysis. Olfactory bulb was used as a positive control tissue; it expressed both HCN isoforms as has been previously reported (Notomi and Shigemoto, 2004). Liver was used as negative control tissue and no HCN isoforms were detected, as previously reported (Arroyo et al., 2006). Bands immunoreactive for HCN1 and HCN2 antibodies were detected in both trigeminal ganglia and rat olfactory bulb (Fig. 1A).
Discussion
The present results show that levels of HCN protein in the trigeminal ganglion are increased and the proportion of dura projecting neurons that are immunoreactive for HCN more than doubles 3–4 days after an inflammation of the dura is induced. These increases were not observed after treatment with buprenorphine.
Conclusion
The present work shows that inflammation of the dura causes an increase in the protein levels and in the numbers of HCN1 and HCN2 expressing neurons in the trigeminal ganglion. These increases were not seen following buprenorphine treatment. These data suggest that HCN1 and HCN2 may contribute to inflammation-induced hyperexcitability and that one mechanism of opioid-mediated reduction of inflammatory hypersensitivity is to prevent upregulation of HCN protein. These data have potential
Acknowledgments
This work was supported by the National Health and Medical Research Council (Australia; grant # 454606). The authors thank Dr. Paul Strijbos (GlaxoSmithKline) for supplying the anti-HCN1 and anti-HCN2 antibodies. The authors thank Prof. Colin Anderson, Dr. Jason Ivanusic and Mr. Michael Williams for their helpful discussions.
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2023, Neurochemistry InternationalCitation Excerpt :Studies have shown that the hyperactivity of HCN channels drive abnormal discharge, resulting in hyperexcitability of sensory neurons, which contributes to the development of pathological pain (Ma et al., 2021; Robinson and Siegelbaum, 2003). Moreover, studies have shown that blockage of HCN channels significantly reduce the ectopic discharges and pain behaviors caused by inflammation and peripheral nerve injury (Chaplan et al., 2003; Emery et al., 2011; Notomi and Shigemoto, 2004; Schnorr et al., 2014; Cho et al., 2009; Lee et al., 2005; Sun et al., 2005; Takasu et al., 2010; Yao et al., 2003). In this study, the amplitude of Ih in vlPAG neurons of bone cancer rats was significantly up regulated, leading to hyperexcitability of vlPAG neurons, which may impair the function of descending endogenous analgesia system and promote bone cancer pain.
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2018, Biochemical PharmacologyCitation Excerpt :Major HCN transcripts in DRG are HCN1 and HCN2 [245,246]. HCN1 and HCN2 are also expressed in trigeminal ganglion [247]. Since HCN is the key regulator for cardiac rhythmic activity, HCN channel blockers, particularly inhibitors of the major sinoatrial isoform, HCN4, are suited for lowering heart rate.