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Capsazepine decreases corneal pain syndrome in severe dry eye disease

Authors
  • Fakih, Darine1, 2
  • Guerrero-Moreno, Adrian1
  • Baudouin, Christophe1, 3, 4
  • Goazigo, Annabelle Réaux-Le1
  • Parsadaniantz, Stéphane Mélik1
  • 1 Institut de la Vision, 17 rue Moreau, Paris, F-75012, France , Paris (France)
  • 2 Laboratoires Théa, 12 rue Louis Biérot, Clermont-Ferrand, F-63000, France , Clermont-Ferrand (France)
  • 3 INSERM-DGOS CIC 1423, 17 rue Moreau, Paris, F-75012, France , Paris (France)
  • 4 University of Versailles Saint-Quentin-en-Yvelines, 9 avenue Charles de Gaulle, Boulogne-Billancourt, F-92100, France , Boulogne-Billancourt (France)
Type
Published Article
Journal
Journal of Neuroinflammation
Publisher
Springer (Biomed Central Ltd.)
Publication Date
May 11, 2021
Volume
18
Issue
1
Identifiers
DOI: 10.1186/s12974-021-02162-7
Source
Springer Nature
Keywords
License
Green

Abstract

BackgroundDry eye disease (DED) is a multifactorial disease of the ocular surface accompanied by neurosensory abnormalities. Here, we evaluated the effectiveness of transient receptor potential vanilloid-1 (TRPV1) blockade to alleviate ocular pain, neuroinflammation, and anxiety-like behavior associated with severe DED.MethodsChronic DED was induced by unilateral excision of the Harderian and extraorbital lacrimal glands of adult male mice. Investigations were conducted at 21 days after surgery. The mRNA levels of TRPV1, transient receptor potential ankyrin-1 (TRPA1), and acid-sensing ion channels 1 and 3 (ASIC1 and ASIC3) in the trigeminal ganglion (TG) were evaluated by RNAscope in situ hybridization. Multi-unit extracellular recording of ciliary nerve fiber activity was used to monitor spontaneous and stimulated (cold, heat, and acid) corneal nerve responsiveness in ex vivo eye preparations. DED mice received topical instillations of the TRPV1 antagonist (capsazepine) twice a day for 2 weeks from d7 to d21 after surgery. The expression of genes involved in neuropathic and inflammatory pain was evaluated in the TG using a global genomic approach. Chemical and mechanical corneal nociception and spontaneous ocular pain were monitored. Finally, anxiety-like behaviors were assessed by elevated plus maze and black and white box tests.ResultsFirst, in situ hybridization showed DED to trigger upregulation of TRPV1, TRPA1, ASIC1, and ASIC3 mRNA in the ophthalmic branch of the TG. DED also induced overexpression of genes involved in neuropathic and inflammatory pain in the TG. Repeated instillations of capsazepine reduced corneal polymodal responsiveness to heat, cold, and acidic stimulation in ex vivo eye preparations. Consistent with these findings, chronic capsazepine instillation inhibited the upregulation of genes involved in neuropathic and inflammatory pain in the TG of DED animals and reduced the sensation of ocular pain, as well as anxiety-like behaviors associated with severe DED.ConclusionThese data provide novel insights on the effectiveness of TRPV1 antagonist instillation in alleviating abnormal corneal neurosensory symptoms induced by severe DED, opening an avenue for the repositioning of this molecule as a potential analgesic treatment for patients suffering from chronic DED.

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