Effects of Peripheral Nerve Injury on the Induction of c-Fos and Phosphorylated ERK in the Brainstem Trigeminal Sensory Nuclear Complex

Abstract

Background Sequential changes in brainstem and spinal cord neurons after traumatic injury to peripheral nerves are related to neuropathic pain symptoms. Purpose This study was conducted to elucidate the influence of nerve insult on stimulus-induced c-Fos expression and ERK phosphorylation by brainstem neurons. Methods The brainstem trigeminal sensory nuclear complex (BTSNC) was examined for neuronal profiles immunolabeled with c-Fos and phosphorylated ERK (p-ERK) antibodies elicited by stimulation of the tongue with capsaicin after lingual or inferior alveolar nerve (IAN) injury. Results Abundant neuronal profiles immunolabeled for c-Fos and p-ERK elicited by capsaicin were distributed in the spinal trigeminal nucleus caudalis (Vc) without nerve injury. The spinal trigeminal nucleus oralis (Vo) contained limited numbers of these neuronal profiles after stimulation of the tongue. A significant reduction of these neuronal profiles in the ipsilateral Vc was detected after lingual nerve injury. After IAN injury, an increased number of neuronal profiles immunolabeled for c-Fos elicited by capsaicin was noted, while that of p-ERK was left unchanged in the ipsilateral Vc. On the both sides of the Vo, an increased number of capsaicin-induced neuronal profiles immunolabeled for c-Fos and p-ERK was detected after lingual or IAN injury. Conclusion Differential effects of lingual or IAN injury on stimulus-induced c-Fos expression and ERK phosphorylation by Vo and Vc neurons may be involved in the complex nature of symptoms of trigeminal neuralgia.