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Item Induction of chronic migraine phenotypes in a rat model after environmental irritant exposure(Lippincott, Williams & Wilkins, 2018-03) Kunkler, Phillip Edward; Zhang, LuJuan; Johnson, Philip Lee; Oxford, Gerry Stephen; Hurley, Joyce Harts; Biochemistry and Molecular Biology, School of MedicineAir pollution is linked to increased emergency department visits for headache and migraine patients frequently cite chemicals or odors as headache triggers, but the association between air pollutants and headache is not well understood. We previously reported that chronic environmental irritant exposure sensitizes the trigeminovascular system response to nasal administration of environmental irritants. Here, we examine whether chronic environmental irritant exposure induces migraine behavioral phenotypes. Male rats were exposed to acrolein, a transient receptor potential channel ankyrin-1 (TRPA1) agonist, or room air by inhalation for 4 days before meningeal blood flow measurements, periorbital cutaneous sensory testing, or other behavioral testing. Touch-induced c-Fos expression in trigeminal nucleus caudalis was compared in animals exposed to room air or acrolein. Spontaneous behavior and olfactory discrimination was examined in open-field testing. Acrolein inhalation exposure produced long-lasting potentiation of blood flow responses to a subsequent TRPA1 agonist and sensitized cutaneous responses to mechanical stimulation. C-Fos expression in response to touch was increased in trigeminal nucleus caudalis in animals exposed to acrolein compared with room air. Spontaneous activity in an open-field and scent preference behavior was different in acrolein-exposed compared with room air-exposed animals. Sumatriptan, an acute migraine treatment blocked acute blood flow changes in response to TRPA1 or transient receptor potential vanilloid receptor-1 agonists. Pretreatment with valproic acid, a prophylactic migraine treatment, attenuated the enhanced blood flow responses observed after acrolein inhalation exposures. Environmental irritant exposure yields an animal model of chronic migraine in which to study mechanisms for enhanced headache susceptibility after chemical exposure.Item Morphologic Changes in the Mandibular Condyle of Growing Sprague-Dawley Rats After Electrolytic Lesioning of the Trigeminal Motor Nucleus(1994) Hurst, Charles A.; Byrd, Kenneth E.; Roberts, W. Eugene; Garetto, Lawrence P.; Hohlt, William; Burr, DavidLesioning motoneurons in the brainstem alters biomechanical forces and affects craniofacial growth by producing skeletal asymmetries. The purpose of this study was to examine changes that occur in the mandibular condyle in rats that have had their trigeminal motor nucleus (TMN) lesioned. The following null hypothesis was tested: unilateral electrolytic lesioning of the TMN has no effect on condylar morphology in growing rats. To accomplish this, experimental rats received a small electrolytic lesion in their left side TMN. The controls received a sham lesion that caused TMN stimulation with no electrolytic lesion produced. Seven rats from each group were sacrificed at 28, 56, and 84 days postoperatively. The rats were decapitated and their skulls were dried. Mandibular condyles were harvested from the dry rat skulls. The specimens were embedded and sectioned. The sections were stained with H&E. The following parameters were measured: condyle perimeter, condylar widths at 125 μm increments measured with a grid aligned with the condylar neck, width of the condylar neck, and bone surface area proximal to the condylar neck measurement. Experimental groups were compared with control groups by means of factorial analysis of variance, ANOVA, with the factors being the experimental operation and the time of sacrifice. Findings show significant or near borderline significant F tests for right-left differences and side-by-group interactions for width at 625 μm, 750 μm, 875 μm, and 1000 μm from the top of the condyle; but not at the other widths measured. Right-left difference and side-by-time interaction for shape factor measurement were also shown to be significant. The null hypothesis stating unilateral electrolytic lesioning of the TMN has no effect on condylar morphology in growing rats was therefore rejected. The failure to reach significance in some parameters may have been due to the small number of specimens. Due to the fragile nature of the dried specimens, group numbers ranged from seven to four condyle pairs per group. In conclusion, lesions to the TMN of growing rats affect the morphology of the mandibular condyle in the medial-lateral plane. Alterations in morphology during growth after lesioning the TMN were likely caused by changes in the neuromuscular activity of masticatory muscles and their biomechanical effects on bone. Data in this study suggest that it is valuable to view mandibular condyles from a frontal view (i.e., frontal tomography) when altered condylar morphology in human patients is suspected.