Abstract
Primary headaches are often associated with pain in the maxillofacial region commonly classified under the term “orofacial pain” (OFP). In turn, long-lasting OFP can trigger and perpetuate headache as an independent entity, which is able to persist after the resolution of the main disorder. A close association between OFP and headache complicates their cause and effect definition and leads to misdiagnosis. The precise mechanisms underlying this phenomenon are poorly understood, partly because of the deficiency of research-related findings. We combined the animal models of OFP and headache—the orofacial formalin test and the model of trigeminovascular nociception—to investigate the neurophysiological mechanisms underlying their comorbidity. In anesthetized rats, the ongoing activity of single convergent neurons in the spinal trigeminal nucleus was recorded in parallel to their responses to the electrical stimulation of the dura mater before and after the injection of formalin into their cutaneous receptive fields. Subcutaneous formalin resulted not only in the biphasic increase in the ongoing activity, but also in an enhancement of neuronal responses to dural electrical stimulation, which had similar time profile. These results demonstrated that under tonic pain in the orofacial region a nociceptive signaling from the dura mater to convergent trigeminal neurons is significantly enhanced apparently because of the development of central sensitization; this may contribute to the comorbidity of OFP and headache.
Highlights
Primary headaches, especially migraine and tension-type headaches, are often associated with pain in the maxillofacial region commonly classified under the term ‘‘orofacial pain’’ (OFP) [1, 2]
Trigeminal neurons demonstrating biphasic increase in ongoing activity after subcutaneous formalin were characterized by the enhancement of responses to electrical stimulation of the dura mater with similar time profile. This is the first study to demonstrate that subcutaneous injection of formalin into the orofacial receptive field of the spinal trigeminal nucleus (STN) neurons results in biphasic increase in their ongoing activity, and in an equal enhancement of neuronal responses to electrical stimulation of the dura mater, which has similar time profile
A group of trigeminal neurons, unresponsive to subcutaneous formalin, was revealed and it did not demonstrate any changes in their ongoing activity or in evoked firing
Summary
Especially migraine and tension-type headaches, are often associated with pain in the maxillofacial region commonly classified under the term ‘‘orofacial pain’’ (OFP) [1, 2]. The latter usually accompanies the temporomandibular joint disorders (TMD), masticatory myofascial lesions as well as sinus-related and odontogenic inflammation or tumor [3, 4]. Close relationship between OFP and headache complicates their cause and effect definition and often serves as a reason to classify these pain syndromes together [3]. Patients with primary headaches are more likely than healthy people to demonstrate dysfunctions in the jaw area, which are commonly attributed to TMD [1, 10]
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