Nociceptive craniofacial muscle primary afferent neurons synapse in both the rostral and caudal brain stem

J Neurophysiol. 2007 Jul;98(1):214-23. doi: 10.1152/jn.00990.2006. Epub 2007 May 9.


Limited information is available on muscle afferent neurons with fine fibers despite their presumed participation in musculoskeletal disorders, including temporomandibular disorders. To study these neurons, intracellular recordings were made from the central axons of slowly conducting muscle afferent neurons in anesthetized rats. After intraaxonal impalement, axons were characterized by masseter nerve stimulation, receptive field testing, muscle stretching and intramuscular injection of hypertonic saline. Intracellular recordings were made from 310 axons (conduction velocity: 6.5-60(M)/s, mean = 27.3(M)/s; following frequency: 27-250 Hz, mean = 110Hz). No neurons responded to cutaneous palpation or muscle stretching. Some axons (n = 34) were intracellularly stained with biotinamide. These neurons were classified as group II/III noxious mechanoreceptors because their mechanical threshold exceeded 15 mN, and conduction velocities ranged from 12 to 40.2(M)/s (mean = 25.3(M)/s). Two morphological types were recognized by using an object-based, three-dimensional colocalization methodology to locate synapses. One type (IIIHTM(Vp-Vc)) possessed axon collaterals that emerged along the entire main axon and synapsed in the trigeminal principal sensory nucleus and spinal trigeminal subnuclei oralis (Vo), interpolaris (Vi), and caudalis (Vc). A second type (IIIHTM(Vo-Vc)) possessed axon collaterals that synapsed only in caudal Vo, Vi, and Vc. Our previous studies show that muscle spindle afferent neurons are activated by innocuous stimuli and synapse in the rostral and caudal brain stem; here we demonstrate that nociceptive muscle mechanoreceptor afferent axons also synapse in rostral and caudal brain stem regions. Traditional dogma asserts that the most rostral trigeminal sensory complex exclusively processes innocuous somatosensory information, whereas caudal portions receive nociceptive sensory input; the data reported here do not support this paradigm.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Afferent Pathways / physiopathology
  • Animals
  • Brain Stem / cytology*
  • Evoked Potentials / physiology
  • Facial Pain / chemically induced
  • Facial Pain / pathology*
  • Imaging, Three-Dimensional / methods
  • Male
  • Masseter Muscle / innervation*
  • Microscopy, Confocal
  • Neurons, Afferent / cytology*
  • Neurons, Afferent / physiology
  • Physical Stimulation / methods
  • Rats
  • Rats, Sprague-Dawley
  • Saline Solution, Hypertonic
  • Synapses / physiology*
  • Synaptophysin / metabolism


  • Saline Solution, Hypertonic
  • Synaptophysin