Purchase this article with an account.
Brendan Kenyon, Deshea L Harris, Fangfang Qiu, Cecilia Chao, Yashar Seyed-Razavi, Pedram Hamrah; Molecular Alterations in Trigeminal Ganglia following Ciliary Nerve Ligation Model of Neuropathic Corneal Pain. Invest. Ophthalmol. Vis. Sci. 2020;61(7):4085.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Inflammatory cytokines and ion channels are known to be involved in neuropathic pain mechanisms. Neurotrophic factors are known to be upregulated following nerve injury, and, although their precise role in neuropathic pain remains controversial, they are upregulated following induction of neuropathic pain. Thus, our aim was to characterize changes in inflammatory cytokines, neurotrophins, and pain-related ion channels within the trigeminal ganglion (TG) following induction of neuropathic corneal pain (NCP) by ciliary nerve ligation.
Adult 7-8 week-old male mice underwent ciliary nerve ligation for the induction of NCP or a sham surgery (n=5/group). Clinical outcomes included corneal fluorescein staining (CFS), sensory testing by Cochet-Bonnet esthesiometry, and application of 10 μL of [5M] saline, cold saline, and L-menthol, as well as paw wipe response within 30s following application. At 14 days post-surgery (dps), the TGs were excised and RNA isolated for qRT-PCR analysis of cytokines (IL-1β, IL-6, and TNFα), neurotrophic factors (NGF, BDNF, NT-3, and CNTF) and pain-related ion channels (P2X4 and P2X7).
Ligation did not significantly alter CFS or Cochet-Bonnet esthesiometry measures between groups (p > 0.05). Application of [5M] saline led to a sustained increase in paw wipe response in NCP vs. sham animals (p<0.001); however, there was no difference in response to cold saline or L-menthol. qRT-PCR results indicated that there was a significant 4.83-fold increase in IL-1β (p<0.05), a 1.63-fold increase in TNFα approaching significance (p = 0.072), and no change in IL-6 expression (p>0.05) at the mRNA level. For neurotrophic factors, there was a 1.96-fold increase in NT-3 (p<0.01), a 1.53-fold increase in BDNF (p<0.01), a 3.06-fold increase in CNTF (p<0.05), and 2.35-fold increase in NGF (p=0.066). Additionally, for select ion channels involved in pain, there was a 2.17-fold increase in P2X7 (p<0.05), and a 2.34-fold increase in P2X4 (p=0.071).
Our model recapitulates features of NCP, such as an enhanced response to [5M] saline challenge and altered expression of markers related to neuropathic pain within the TG. Within our NCP model, IL-1β, P2X7, BDNF, NT-3, and CNTF are significantly upregulated. Thus, our model recapitulates clinical and molecular features of neuropathic pain and will enable the elucidation of NCP mechanisms.
This is a 2020 ARVO Annual Meeting abstract.
This PDF is available to Subscribers Only