Neurophysiology of Orofacial Pain

  • Koichi IwataEmail author
  • Mamoru Takeda
  • Seog Bae Oh
  • Masamichi Shinoda
Reference work entry


It is well known that unmyelinated C-fibers and small-diameter Aδ-fibers innervate the orofacial skin, mucous membrane, orofacial muscles, teeth, tongue, and temporomandibular joint. Peripheral terminals consist of free nerve endings, and thermal and mechanical receptors such as transient receptor potential (TRP) channels and purinergic receptors exist in nerve endings. Ligands for each receptor are released from peripheral tissues following a variety of noxious stimuli applied to the orofacial region and bind to these receptors, following which action potentials are generated in these fibers and conveyed mainly to the trigeminal spinal subnucleus caudalis (Vc) and upper cervical spinal cord (C1-C2). Neurons receiving noxious inputs from the orofacial regions are somatotopically organized in the Vc and C1-C2. The third branch (mandibular nerve) of the trigeminal nerve innervates the dorsal portion of the Vc, and the first branch (ophthalmic nerve) of the trigeminal nerve innervates the ventral part of the Vc; the middle portion of them receives the second branch (maxillary nerve) of the trigeminal nerve. Various neurotransmitters such as glutamate and substance P (SP) are released from primary afferent terminals and bind to receptors such as AMPA and NMDA glutamate receptors and neurokinin 1 receptors in Vc and C1-C2 nociceptive neurons. Further, noxious information from the orofacial region reaching Vc and C1-C2 is sent to the somatosensory and limbic cortices via the ventral posterior medial thalamic nucleus (VPM) and medial thalamic nuclei (parafascicular nucleus, centromedial nucleus, and medial dorsal nucleus), respectively, and finally, orofacial pain sensation is perceived. It is also known that descending pathways in the brain act on Vc and C1-C2 nociceptive neurons to modulate pain signals. Under pathological conditions such as trigeminal nerve injury or orofacial inflammation, trigeminal ganglion (TG) neurons become hyperactive, and a barrage of action potentials is generated in TG neurons, and these are sensitized a long time after the hyperactivation of TG neurons. Furthermore, there is an increase in Vc and C1-C2 neuronal activities, and these neurons can be sensitized in association with TG-neuron sensitization, and then orofacial pain hypersensitivity can occur. Recent studies have also reported that glial cells are involved in pathological orofacial pain states related to trigeminal nerve injury and orofacial inflammation. Peripheral and central mechanisms of orofacial pain under physiologic and pathologic conditions are viewed in this chapter, and future insights regarding the pathogenesis of persistent orofacial pain are discussed.


Trigeminal nerve Orofacial pain Brainstem Medial system Lateral system Descending modulation Persistent pain 


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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Koichi Iwata
    • 1
    Email author
  • Mamoru Takeda
    • 2
  • Seog Bae Oh
    • 3
  • Masamichi Shinoda
    • 1
  1. 1.Department of Physiology, School of DentistryNihon UniversityTokyoJapan
  2. 2.Laboratory of Food and Physiological Sciences, Department of Food and Life Sciences, School of Life and Environmental SciencesAzabu UniversitySagamiharaJapan
  3. 3.Department of Neurobiology and Physiology, School of DentistrySeoul National UniversitySeoulRepublic of Korea

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