Involvement of oxidative stress in orofacial mechanical pain hypersensitivity following neonatal maternal separation in rats

Chihiro Soma, Suzuro Hitomi, Eri Oshima, Yoshinori Hayashi, Kumi Soma, Ikuko Shibuta, Yoshiyuki Tsuboi, Tetsuo Shirakawa, Takashi Kikuiri, Koichi Iwata, Masamichi Shinoda

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Patients with persistent pain have sometimes history of physical abuse or neglect during infancy. However, the pathogenic mechanisms underlying orofacial pain hypersensitivity associated with early-life stress remain unclear. The present study focused on oxidative stress and investigated its role in pain hypersensitivity in adulthood following early-life stress. To establish an early-life stress model, neonatal pups were separated with their mother in isolated cages for 2 weeks. The mechanical head-withdrawal threshold (MHWT) in the whisker pad skin of rats received maternal separation (MS) was lower than that of non-MS rats at postnatal week 7. In MS rats, the expression of 8-hydroxy-deoxyguanosine, a marker of DNA oxidative damage, was enhanced, and plasma antioxidant capacity, but not mitochondrial complex I activity, decreased compared with that in non-MS rats. Reactive oxygen species (ROS) inactivation and ROS-sensitive transient receptor potential ankyrin 1 (TRPA1) antagonism in the whisker pad skin at week 7 suppressed the decrease of MHWT. Corticosterone levels on day 14 increased in MS rats. Corticosterone receptor antagonism during MS periods suppressed the reduction in antioxidant capacity and MHWT. The findings suggest that early-life stress potentially induces orofacial mechanical pain hypersensitivity via peripheral nociceptor TRPA1 hyperactivation induced by oxidative stress in the orofacial region.

Original languageEnglish
Article number22760
JournalScientific Reports
Volume13
Issue number1
DOIs
Publication statusPublished - Dec 2023

Fingerprint

Dive into the research topics of 'Involvement of oxidative stress in orofacial mechanical pain hypersensitivity following neonatal maternal separation in rats'. Together they form a unique fingerprint.

Cite this