title: Evidence for TRPA1 involvement in central neural mechanisms in a rat model of dry eye.
abstract: Dry eye (DE) disease is commonly associated with ocular surface inflammation, an unstable tear film and symptoms of irritation. However, little is known about the role of central neural mechanisms in DE. This study used a model for persistent aqueous tear deficiency, exorbital gland removal, to assess the effects of mustard oil (MO), a transient receptor potential ankyrin (TRPA1) agonist, on eyeblink and eyewipe behavior and Fos-like immunoreactivity (Fos-LI) in the trigeminal brainstem of male rats. Spontaneous tear secretion was reduced by about 50% and spontaneous eyeblinks were increased more than 100% in DE rats compared to sham rats. MO (0.02-0.2%) caused dose-related increases in eyeblink and forelimb eyewipe behavior in DE and sham rats. Exorbital gland removal alone was sufficient to increase Fos-LI at the ventrolateral pole of trigeminal interpolaris/caudalis (Vi/Vc) transition region, but not at more caudal regions of the trigeminal brainstem. Under barbiturate anesthesia ocular surface application of MO (2-20%) produced Fos-LI in the Vi/Vc transition, in the mid-portions of Vc and in the trigeminal caudalis/upper cervical spinal cord (Vc/C1) region that was significantly greater in DE rats than in sham controls. MO caused an increase in Fos-LI ipsilaterally in superficial laminae at the mid-Vc and Vc/C1 regions in a dose-dependent manner. Smaller, but significant, increases in Fos-LI also were seen in the contralateral Vc/C1 region in DE rats. TRPA1 protein levels in trigeminal ganglia from DE rats ipsilateral and contralateral to gland removal were similar. Persistent tear reduction enhanced the behavioral and trigeminal brainstem neural responses to ocular surface stimulation by MO. These results suggested that TRPA1 mechanisms play a significant role in the sensitization of ocular-responsive trigeminal brainstem neurons in this model for tear deficient DE.
authors: Department of Diagnostic and Biological Sciences, University of Minnesota School of Dentistry, Moos Tower 18-214, 515 Delaware Street SE, Minneapolis, MN 55455, USA.
authors: A
authors: A
authors: Katagiri
authors: Department of Diagnostic and Biological Sciences, University of Minnesota School of Dentistry, Moos Tower 18-214, 515 Delaware Street SE, Minneapolis, MN 55455, USA.
authors: R
authors: R
authors: Thompson
authors: Department of Diagnostic and Biological Sciences, University of Minnesota School of Dentistry, Moos Tower 18-214, 515 Delaware Street SE, Minneapolis, MN 55455, USA.
authors: M
authors: M
authors: Rahman
authors: Department of Diagnostic and Biological Sciences, University of Minnesota School of Dentistry, Moos Tower 18-214, 515 Delaware Street SE, Minneapolis, MN 55455, USA.
authors: K
authors: K
authors: Okamoto
authors: Department of Diagnostic and Biological Sciences, University of Minnesota School of Dentistry, Moos Tower 18-214, 515 Delaware Street SE, Minneapolis, MN 55455, USA. Electronic address: bereiter@umn.edu.
authors: D A
authors: DA
authors: Bereiter
mesh_terms: D000818:Animals; D001767:Blinking / Q000187:drug effects / Q000502:physiology; D001933:Brain Stem / Q000187:drug effects / Q000503:physiopathology*; D002491:Central Nervous System Agents / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D015352:Dry Eye Syndromes / Q000503:physiopathology*; D005552:Forelimb / Q000503:physiopathology; D007839:Functional Laterality; D015151:Immunoblotting; D007150:Immunohistochemistry; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009149:Mustard Plant; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010784:Photomicrography; D010938:Plant Oils / Q000494:pharmacology; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels / Q000819:agonists / Q000378:metabolism*; D013666:Tears / Q000187:drug effects / Q000378:metabolism; D012668:Trigeminal Ganglion / Q000187:drug effects / Q000503:physiopathology*
chemical_list: D002491:Central Nervous System Agents; D010938:Plant Oils; D016760:Proto-Oncogene Proteins c-fos; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels; C480976:Trpa1 protein, rat; C027793:mustard oil
keywords: TRPA1; c-Fos; central sensitization; dry eye; eyeblink behavior
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