Differential induction of c-Fos and phosphorylated ERK by a noxious stimulus after peripheral nerve injury

ABSTRACT

Purpose: In this study, we compared induction of c-Fos and phosphorylated extracellular signal-regulated kinase (p-ERK) in the spinal dorsal horn after peripheral nerve injury.

Materials and methods: We examined the spinal dorsal horn for noxious heat-induced c-Fos and p-ERK protein-like immunoreactive (c-Fos- and p-ERK-IR) neuron profiles after tibial nerve injury. The effect of administration of a MEK 1/2 inhibitor (PD98059) on noxious heat-induced c-Fos expression was also examined after tibial nerve injury.

Results: A large number of c-Fos- and p-ERK-IR neuron profiles were induced by noxious heat stimulation to the hindpaw in sham-operated animals. A marked reduction in the number of c-Fos- and p-ERK-IR neuron profiles was observed in the medial 1/3 (tibial territory) of the dorsal horn at 3 and 7 days after nerve injury. Although c-Fos-IR neuron profiles had reappeared by 14 days after injury, the number of p-ERK-IR neuron profiles remained decreased in the tibial territory of the superficial dorsal horn. Double immunofluorescence labeling for c-Fos and p-ERK induced by noxious heat stimulation to the hindpaw at different time points revealed that a large number of c-Fos-IR, but not p-ERK-IR, neuron profiles were distributed in the tibial territory after injury. Although administration of a MEK 1/2 inhibitor to the spinal cord suppressed noxious heat-induced c-Fos expression in the peroneal territory, this treatment did not alter c-Fos induction in the tibial territory after nerve injury.

Conclusions: ERK phosphorylation may be involved in c-Fos induction in normal nociceptive responses, but not in exaggerated c-Fos induction after nerve injury.

KEYWORDS:

• c-Fos
• ERK phosphorylation
• nerve injury
• spinal dorsal horn
• neuropathic pain

Disclosure statement

The authors do not have any conflict of interest.

Additional information

Funding

This study was supported by a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science [grant number 16K11440].

Notes on contributors

Mitsuyasu Tabata

Mitsuyasu Tabata, DDS, is a fourth-year graduate student in Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences. He received a bachelor's degree in dentistry (6 years) from Okayama University.

Ryuji Terayama

Ryuji Terayama, DDS, PhD, is an associate professor in the Department of Oral Function and Anatomy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences. He received a bachelor's degree in dentistry (6 years) from Kyushu Dental College. He received his PhD (Medical science) from Miyazaki Medical College.

Kotaro Maruhama

Kotaro Maruhama, DDS, PhD, is an assistant professor in the Department of Oral Function and Anatomy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences. He received a bachelor's degree in dentistry (6 years) from Okayama University. He received his PhD (Dental science) from Okayama University.

Seiji Iida

Seiji Iida, DDS, PhD, is a professor in the Department of Oral and Maxillofacial Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences. He received a bachelor's degree in dentistry (6 years) from Osaka University. He received his PhD (Dental science) from Osaka University.

Tomosada Sugimoto

Tomosada Sugimoto, DDS, PhD, is a professor in the Department of Oral Function and Anatomy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences. He received a bachelor's degree in dentistry (6 years) from Osaka University. He received his PhD (Dental science) from Osaka University.