Orofacial deep and cutaneous tissue inflammation and trigeminal neuronal activation: Implications for persistent temporomandibular pain

Hiroki Imbe, Koichi Iwata, Qi Qi Zhou, Shiping Zou, Ronald Dubner, Ke Ren

Research output: Contribution to journalArticlepeer-review

101 Scopus citations


A rat model has been developed to characterize the responses of brainstem trigeminal neurons to orofacial deep and cutaneous tissue inflammation and hyperalgesia. Complete Freund's adjuvant (CFA) was injected unilaterally into the rat temporomandibular joint (TMJ) or perioral (PO) skin to produce inflammation in deep or cutaneous tissues, respectively. The TMJ and PO inflammation resulted in orofacial behavioral hyperalgesia and allodynia that peaked within 4-24 h and persisted for at least 2 weeks. Compared to cutaneous CFA injection, the injection of CFA into the TMJ produced a significantly stronger inflammation associated with a selective upregulation of preprodynorphin mRNA in the trigeminal spinal complex, an enhanced medullary dorsal horn hyperexcitability, and a greater trigeminal Fos protein expression, a marker of neuronal activation. The Fos-LI induced by TMJ inflammation persisted longer, was more intense, particularly in the superficial laminae, and more widespread rostrocaudally. Thus, the inflammatory irritant produces a stronger effect in deep than in cutaneous orofacial tissue. As there is heavy innervation of the TMJ by unmyelinated nerve endings, a strong nociceptive primary afferent barrage is expected following inflammation. An increase in TMJ C-fiber input after inflammation and strong central neuronal activation may initiate central hyperexcitability and contribute to persistent pain associated with temporomandibular disorders. Since deep inputs may be more effective in inducing central neuronal excitation than cutaneous inputs, greater sensory disturbances may occur in pain conditions involving deep tissues than in those involving cutaneous tissues.

Original languageEnglish (US)
Pages (from-to)238-247
Number of pages10
JournalCells Tissues Organs
Issue number3
StatePublished - 2001
Externally publishedYes


  • Complete Freund's adjuvant
  • Evans' blue extravasation
  • Fos protein
  • Paratrigeminal nucleus
  • Preprodynorphin gene

ASJC Scopus subject areas

  • Anatomy
  • Histology


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