Sensitization of trigeminal brainstem pathways in a model for tear deficient dry eye

Md. M Rahman, Keiichiro Okamoto, Randall Thompson, Ayano Katagiri, David A Bereiter

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52 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)942-950
Number of pages9
Issue number5
StatePublished - May 1 2015

Bibliographical note

Publisher Copyright:
© 2015 International Association for the Study of Pain.


  • Central sensitization
  • Dry eye
  • Electromyography
  • Ocular pain
  • Orbicularis oculi
  • Synaptic blockade
  • Trigeminal brainstem


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