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Quintessence Publishing: Journals: OFPH
Journal of Oral & Facial Pain and Headache

Edited by Barry J. Sessle, BDS, MDS, BSc, PhD, FRSC

Official Journal of the American Academy of Orofacial Pain,
the European, Asian, and Ibero-Latin Academies of Craniomandibular
Disorders, and the Australian Academy of Orofacial Pain

ISSN 2333-0384 (print) • ISSN 2333-0376 (online)

Fall 2004
Volume 18 , Issue 4

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Brainstem Mechanisms of Persistent Pain Following Injury

Ronald Dubner, DDS, PhD/Ke Ren, MD, PhD

Pages: 299 - 305
PMID: 15636012

Nerve signals arising from sites of tissue or nerve injury lead to long-term changes in the central nervous system and contribute to hyperalgesia and the amplification and persistence of pain. These nociceptor activity–dependent changes are referred to as central sensitization. Central sensitization involves an increase in the excitability of medullary dorsal horn (subnucleus caudalis) and spinal dorsal horn neurons brought about by a series of events including neuronal depolarization; removal of the voltage-dependent magnesium block of the N-methyl-D-aspartate (NMDA) receptor; release of calcium from intracellular stores; phosphorylation of the NMDA, alpha amino-3-hydroxy-5-methyl-4-isoxazole-propionate (AMPA), and neurokinin (NK) 1 receptors via activation of protein kineses; a change in the neuron’s excitability; and an increase in synaptic strength. Central sensitization occurs in trigeminal nociceptive pathways, and more robust neuronal hyperexcitability occurs following deep tissue stimulation than cutaneous stimulation. Utilizing Fos protein immunocytochemistry, it has been found that 2 distinct regions are activated in the trigeminal brainstem sensory nuclei, the subnuclei interpolaris/caudalis transition zone (Vi/Vc) and the caudal part of the subnucleus caudalis. The latter is very similar to the spinal dorsal horn and is involved in the sensory discriminative aspects of pain. In contrast, the ventral pole of the Vi/Vc is unique. In addition to its role in the nociceptive sensory processing of deep tissues, it is involved bilaterally in somatovisceral and somatoautonomic processing, activation of the pituitary-adrenal axis, and descending modulatory control. The findings support our overall hypothesis that the ventral pole of Vi/Vc is involved in the coordination of bilateral sensorimotor functions of the trigeminal system associated with the response to deep tissue injury.

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