Sensitization of trigeminal brainstem pathways in a model for tear deficient dry eye.
Chronic dry eye disease (DE) is associated with an unstable tear film and symptoms of ocular discomfort. The characteristics of symptoms suggest a key role for central neural processing; however, little is known about central neuroplasticity and DE. We used a model for tear deficient DE and assessed effects on eye blink behavior, orbicularis oculi muscle activity (OOemg), and trigeminal brainstem neural activity in male rats. Ocular-responsive neurons were recorded at the interpolaris/caudalis transition (Vi/Vc) and Vc/upper cervical cord (Vc/C1) regions under isoflurane, whereas OOemg activity was recorded under urethane. Spontaneous tear volume was reduced by ∼50% at 14 days after exorbital gland removal. Hypertonic saline-evoked eye blink behavior in awake rats was enhanced throughout the 14 days after surgery. Saline-evoked neural activity at the Vi/Vc transition and in superficial and deep laminae at the Vc/C1 region was greatly enhanced in DE rats. Neurons from DE rats classified as wide dynamic range displayed enlarged convergent periorbital receptive fields consistent with central sensitization. Saline-evoked OOemg activity was markedly enhanced in DE rats compared with controls. Synaptic blockade at the Vi/Vc transition or the Vc/C1 region greatly reduced hypertonic saline-evoked OOemg activity in DE and sham rats. These results indicated that persistent tear deficiency caused sensitization of ocular-responsive neurons at multiple regions of the caudal trigeminal brainstem and enhanced OOemg activity. Central sensitization of ocular-related brainstem circuits is a significant factor in DE and likely contributes to the apparent weak correlation between peripheral signs of tear dysfunction and symptoms of irritation.
Department of Diagnostic and Biological Sciences, University of Minnesota School of Dentistry, Minneapolis, MN, USA.
Mostafeezur
M
Rahman
Keiichiro
K
Okamoto
Randall
R
Thompson
Ayano
A
Katagiri
David A
DA
Bereiter
D000818:Animals; D001767:Blinking; D001933:Brain Stem / Q000503:physiopathology*; D066193:Cervical Cord / Q000166:cytology / Q000503:physiopathology; D004195:Disease Models, Animal; D015352:Dry Eye Syndromes / Q000503:physiopathology*; D004576:Electromyography; D005123:Eye / Q000378:metabolism / Q000503:physiopathology*; D005143:Eyelids / Q000503:physiopathology; D008297:Male; D018482:Muscle, Skeletal / Q000503:physiopathology; D009434:Neural Pathways / Q000503:physiopathology*; D009915:Orbit / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013666:Tears / Q000378:metabolism*; D014276:Trigeminal Nerve / Q000503:physiopathology*