Journal Article

Trigeminal-Rostral Ventromedial Medulla Circuitry is Involved in Orofacial Hyperalgesia Contralateral to Tissue Injury

Ren, Ke, Chai, Bryan, Dubner, Ronald, Guo, Wei, Wei, Feng

2012

Overview

Background: Our previous studies have shown that complete Freund's adjuvant (CFA)-induced masseter inflammation and microinjection of the pro-inflammatory cytokine interleukin-1β (IL-1β) into the subnucleus interpolaris/subnucleus caudalis transition zone of the spinal trigeminal nucleus (Vi/Vc) can induce contralateral orofacial hyperalgesia in rat models. We have also shown that contralateral hyperalgesia is attenuated with a lesion of the rostral ventromedial medulla (RVM), a critical site of descending pain modulation. Here we investigated the involvement of the RVM-Vi/Vc circuitry in mediating contralateral orofacial hyperalgesia after an injection of CFA into the masseter muscle. Results: Microinjection of the IL-1 receptor antagonist (5 nmol, n=6) into the ipsilateral Vi/Vc attenuated the CFA-induced contralateral hyperalgesia but not the ipsilateral hyperalgesia. Intra-RVM post-treatment injection of the NK1 receptor antagonists, RP67580 (0.5-11.4 nmol) and L-733,060 (0.5-11.4 nmol), attenuated CFA-induced bilateral hyperalgesia and IL-1β induced bilateral hyperalgesia. Serotonin depletion in RVM neurons prior to intra-masseter CFA injection prevented the development of contralateral hyperalgesia 1–3 days after CFA injection. Inhibition of 5-HT3 receptors in the contralateral Vi/Vc with direct microinjection of the select 5-HT3 receptor antagonist, Y-25130 (2.6-12.9 nmol), attenuated CFA-induced contralateral hyperalgesia. Lesions to the ipsilateral Vc prevented the development of ipsilateral hyperalgesia but did not prevent the development of contralateral hyperalgesia. Conclusions: These results suggest that the development of CFA-induced contralateral orofacial hyperalgesia is mediated through descending facilitatory mechanisms of the RVM-Vi/Vc circuitry.

• Publisher: SAGE Publications,BioMed Central,BioMed Central Ltd,Sage Publications Ltd,SAGE Publishing
• Subject: Acids / Analysis / Animals / Antagonists / Behavior / Cytokines / Descending modulation / Facial Pain - complications / Facial Pain - metabolism / Facial Pain - pathology / Freund's Adjuvant / Hyperalgesia - complications / Hyperalgesia - metabolism / Hyperalgesia - pathology / IL-1β / Inflammation / Injections / Injuries / Interleukin 1 receptor antagonist / Interleukins / Intralaminar Thalamic Nuclei - metabolism / Intralaminar Thalamic Nuclei - pathology / Male / masseter muscle / Medicine / Medicine & Public Health / Medulla oblongata / Medulla Oblongata - metabolism / Medulla Oblongata - pathology / Microinjection / Models, Biological / Molecular Medicine / Nerve Net - metabolism / Nerve Net - pathology / Neurobiology / Neurokinin NK1 receptors / Neurokinin-1 Receptor Antagonists / Neurology / Neurons / Neurosciences / Pain / Pain Medicine / Pain perception / Rat / Rats / Rats, Sprague-Dawley / Receptors, Interleukin-1 - antagonists & inhibitors / Receptors, Interleukin-1 - metabolism / Receptors, Neurokinin-1 - metabolism / Receptors, Serotonin, 5-HT3 - metabolism / Reproducibility of Results / Rodents / Serotonin / Serotonin - deficiency / Serotonin - metabolism / Serotonin S3 receptors / Spinal cord / Spinal trigeminal nucleus / Substance P / Trigeminal Caudal Nucleus - metabolism / Trigeminal Caudal Nucleus - pathology / Ventromedial Hypothalamic Nucleus - metabolism / Ventromedial Hypothalamic Nucleus - pathology / Vi/Vc transition zone