Abstract
Obstructive sleep apnea (OSA), characterized by low arterial oxygen saturation during sleep, is associated with an increased risk of orofacial pain. In this study, we simulated chronic intermittent hypoxia (CIH) during the sleep/rest phase (light phase) to determine the role of transient receptor potential vanilloid 1 (TRPV1) in mediating enhanced orofacial nocifensive behavior and trigeminal spinal subnucleus caudalis (Vc) neuronal responses to capsaicin (a TRPV1 agonist) stimulation in a rat model of OSA. Rats were subjected to CIH (nadir O2, 5%) during the light phase for 8 or 16 consecutive days. CIH yielded enhanced behavioral responses to capsaicin after application to the ocular surface and intraoral mucosa, which was reversed under normoxic conditions. The percentage of TRPV1-immunoreactive trigeminal ganglion neurons was greater in CIH rats than in normoxic rats and recovered under normoxic conditions after CIH. The ratio of large-sized TRPV1-immunoreactive trigeminal ganglion neurons increased in CIH rats. The density of TRPV1 positive primary afferent terminals in the superficial laminae of Vc was higher in CIH rats. Phosphorylated extracellular signal-regulated kinase (pERK)-immunoreactive cells intermingled with the central terminal of TRPV1-positive afferents in the Vc. The number of pERK-immunoreactive cells following low-dose capsaicin (0.33 µM) application to the tongue was significantly greater in the middle portion of the Vc of CIH rats than of normoxic rats and recovered under normoxic conditions after CIH. These data suggest that CIH during the sleep (light) phase is sufficient to transiently enhance pain on the ocular surface and intraoral mucosa via TRPV1-dependent mechanisms.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 66-81 |
| Number of pages | 16 |
| Journal | Neuroscience |
| Volume | 483 |
| DOIs | |
| State | Published - Feb 10 2022 |
Bibliographical note
Funding Information:The authors thank Dr. Yoshie Okamoto and Ms. Keiko Nakano of Department of Oral Physiology Osaka University Graduate School of Dentistry and the undergraduate students of Osaka University School of Dentistry – Risa Okamoto, Risa Hayasaki, and Juri Yamada – for their technical assistance to this project. This work was supported by the SHISEIKAI Scholarship Fund for the basic researcher of medical science Keiko Watanabe Award, JSPS KAKENHI [grant numbers #20K18666, #20KK0211], the Foundation of Kinoshita Memorial Enterprise, and a research grant from MSD K.K. (Tokyo, Japan) to AK, and in part by JSPS KAKENHI [grant numbers # 16K11748 to AO, #17K19753 to TK]. We would like to thank Editage ( www.editage.com ) for English language editing.
Funding Information:
The authors thank Dr. Yoshie Okamoto and Ms. Keiko Nakano of Department of Oral Physiology Osaka University Graduate School of Dentistry and the undergraduate students of Osaka University School of Dentistry ? Risa Okamoto, Risa Hayasaki, and Juri Yamada ? for their technical assistance to this project. This work was supported by the SHISEIKAI Scholarship Fund for the basic researcher of medical science Keiko Watanabe Award, JSPS KAKENHI [grant numbers #20K18666, #20KK0211], the Foundation of Kinoshita Memorial Enterprise, and a research grant from MSD K.K. (Tokyo, Japan) to AK, and in part by JSPS KAKENHI [grant numbers # 16K11748 to AO, #17K19753 to TK]. We would like to thank Editage (www.editage.com) for English language editing.
Publisher Copyright:
© 2021 The Authors
Keywords
- TRPV1
- chronic intermittent hypoxia
- hypersensitivity
- pERK
- phenotypic change
- trigeminal nervous system
PubMed: MeSH publication types
- Journal Article
- Research Support, Non-U.S. Gov't