Neonatal Injury Modulates Incisional Pain Sensitivity in Adulthood: An Animal Study

Kumi Soma; Suzuro Hitomi; Yoshinori Hayashi; Chihiro Soma; Jo Otsuji; Ikuko Shibuta; Akihiko Furukawa; Kentaro Urata; Ryoko Kurisu; Mamiko Yonemoto; Yasushi Hojo; Tetsuo Shirakawa; Koichi Iwata; Masamichi Shinoda

doi:10.1016/j.neuroscience.2023.03.018

Neonatal Injury Modulates Incisional Pain Sensitivity in Adulthood: An Animal Study

Neuroscience. 2023 May 21:519:60-72. doi: 10.1016/j.neuroscience.2023.03.018. Epub 2023 Mar 22.

Authors

Affiliations

¹ Department of Pediatric Dentistry, Nihon University School of Dentistry, 1-8-13 Kandasurugadai, Chiyoda-ku, Tokyo 101-8310, Japan.
² Department of Physiology, Nihon University School of Dentistry, 1-8-13 Kandasurugadai, Chiyoda-ku, Tokyo 101-8310, Japan. Electronic address: hitomi.suzuro@nihon-u.ac.jp.
³ Department of Physiology, Nihon University School of Dentistry, 1-8-13 Kandasurugadai, Chiyoda-ku, Tokyo 101-8310, Japan.
⁴ Department of Pediatric Dentistry, Nihon University School of Dentistry, 1-8-13 Kandasurugadai, Chiyoda-ku, Tokyo 101-8310, Japan; Department of Physiology, Nihon University School of Dentistry, 1-8-13 Kandasurugadai, Chiyoda-ku, Tokyo 101-8310, Japan.
⁵ Department of Oral and Maxillofacial Surgery, Nihon University School of Dentistry, 1-8-13 Kandasurugadai, Chiyoda-ku, Tokyo 101-8310, Japan.
⁶ Department of Complete Denture Prosthodontics, Nihon University School of Dentistry, 1-8-13 Kandasurugadai, Chiyoda-ku, Tokyo 101-8310, Japan.
⁷ Department of Physiology, Nihon University School of Dentistry, 1-8-13 Kandasurugadai, Chiyoda-ku, Tokyo 101-8310, Japan; Department of Orofacial Pain Clinic, Tokyo Medical and Dental University Hospital, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.

PMID: 36958596
DOI: 10.1016/j.neuroscience.2023.03.018

Abstract

Neonatal pain experiences including traumatic injury influence negatively on development of nociceptive circuits, resulting in persistent pain hypersensitivity in adults. However, the detailed mechanism is not yet well understood. In the present study, to clarify the pathogenesis of orofacial pain hypersensitivity associated with neonatal injury, the involvement of the voltage-gated sodium channel (Na_v) 1.8 and the C-C chemokine ligand 2 (CCL2)/C-C chemokine receptor 2 (CCR2) signaling in the trigeminal ganglion (TG) in facial skin incisional pain hypersensitivity was examined in 190 neonatal facial-injured and sham male rats. The whisker pad skin was incised on postnatal day 4 and week 7 (Incision-Incision group). Compared to the group without neonatal incision (Sham-Incision group), mechanical hypersensitivity in the whisker pad skin was enhanced in Incision-Incision group. The number of Na_v1.8-immunoreactive TG neurons and the amount of CCL2 expressed in the macrophages and satellite glial cells in the TG were increased on day 14 after re-incision in the Incision-Incision group, compared with Sham-Incision group. Blockages of Na_v1.8 in the incised region and CCR2 in the TG suppressed the enhancement of mechanical hypersensitivity in the Incision-Incision group. Administration of CCL2 into the TG enhanced mechanical hypersensitivity in the Sham-Sham, Incision-Sham and Sham-Incision group. Our results suggest that neonatal facial injury accelerates the TG neuronal hyperexcitability following orofacial skin injury in adult in association with Na_v1.8 overexpression via CCL2 signaling, resulting in the enhancement of orofacial incisional pain hypersensitivity in the adulthood.

Keywords: CCL2; Na(v)1.8; neonatal injury; orofacial pain; trigeminal ganglion.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Facial Pain / pathology
Hyperalgesia* / etiology
Male
Pain Threshold
Rats
Rats, Sprague-Dawley
Skin
Surgical Wound* / complications
Trigeminal Ganglion