title: Trigeminal-rostral ventromedial medulla circuitry is involved in orofacial hyperalgesia contralateral to tissue injury.
abstract: 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-HT(3) receptors in the contralateral Vi/Vc with direct microinjection of the select 5-HT(3) 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.
authors.affiliation: Department of Neural and Pain Sciences, School of Dentistry, University of Maryland, Baltimore, MD 21201, USA.
authors.forename: Bryan
authors.initials: B
authors.lastname: Chai
authors.forename: Wei
authors.initials: W
authors.lastname: Guo
authors.forename: Feng
authors.initials: F
authors.lastname: Wei
authors.forename: Ronald
authors.initials: R
authors.lastname: Dubner
authors.forename: Ke
authors.initials: K
authors.lastname: Ren
mesh_terms: D000818:Animals; D005157:Facial Pain / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D005620:Freund's Adjuvant; D006930:Hyperalgesia / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D007267:Injections; D020646:Intralaminar Thalamic Nuclei / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008526:Medulla Oblongata / Q000378:metabolism / Q000473:pathology*; D008954:Models, Biological; D009415:Nerve Net / Q000378:metabolism / Q000473:pathology*; D064729:Neurokinin-1 Receptor Antagonists; D051381:Rats; D017207:Rats, Sprague-Dawley; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D018040:Receptors, Neurokinin-1 / Q000378:metabolism; D044406:Receptors, Serotonin, 5-HT3 / Q000378:metabolism; D015203:Reproducibility of Results; D012701:Serotonin / Q000172:deficiency / Q000378:metabolism; D014275:Trigeminal Caudal Nucleus / Q000378:metabolism / Q000473:pathology*; D014697:Ventromedial Hypothalamic Nucleus / Q000378:metabolism / Q000473:pathology*
chemical_list: D064729:Neurokinin-1 Receptor Antagonists; D017472:Receptors, Interleukin-1; D018040:Receptors, Neurokinin-1; D044406:Receptors, Serotonin, 5-HT3; D012701:Serotonin; D005620:Freund's Adjuvant