Background & Aims
The cornea is the most densely innervated surface tissue in the body and receives somatosensory and nociceptive afferents from the ophthalmic branch of the trigeminal nerve. Corneal afferents are thought to be the primary source of nociceptive signals in the production of eye pain and may contribute to chronic ocular pain (Belmonte 1997). Functional neuroimaging studies suggest that light-induced pain may activate primary somatosensory cortex (S1) in patients with chronic ocular pain (1-4). Further, blockade of corneal afferents with ophthalmic proparacaine, a topical anesthetic, reduces light-induced pain in a subset of patients with chronic ocular pain (1).
The aim of this study was to determine whether fMRI activity in S1 is functionally correlated with different networks in proparacaine responders vs. non-responders in chronic ocular pain patients while presented with intermittent light stimuli.
Methods
43 subjects (16F:27M, 54.9±11.6 yrs old) with chronic ocular pain and photophobia (average pain rating over 1-week recall ? 1; NPSI-Eye #9 ? 1) were recruited from the Miami Veterans Affairs (VA) Eye Clinic. fMRI was performed (3T MRI Siemens Magnetom VIDA) using the following visual stimuli: a black screen with a white fixation cross (OFF 30s+jitter), and a white screen with a black fixation cross (ON 6s). Subjects rated pain intensity induced by the white screen on a 0-100 numerical rating scale. After the scan, subjects received 0.5% proparacaine in each eye and were presented the same light stimulus in the same way. Subjects were grouped into responders and non-responders based on whether their light-evoked pain ratings decreased after proparacaine. Functional connectivity analysis using CONN Toolbox was performed using the corneal representation in right S1 as the seed (MNI 56,-14,43)(2). Separate maps were created for responders and non-responders and qualitatively compared.
Results
13 patients were classified as proparacaine responders (pain intensity ratings PRE: 52.1±27.7, POST: 20.8±22.5), and 30 as non-responders (PRE: 14.6±24.3, POST: 29.5±33.8). S1-cornea functional connectivity maps revealed both unique and shared areas of connectivity in brain regions in responders and non-responders. Similar areas of connectivity included the bilateral secondary somatosensory cortex (S2), portions of the salience and dorsal attention network, and precentral central gyrus. However, non-responders further demonstrated connectivity between S1 and the left insula, visual cortex (including lateral occipital cortex and occipital pole), superior parietal lobule, angular gyrus, right frontal operculum, right inferior frontal gyrus, cerebellar vermis, and other areas. On the other hand, responders had unique S1-cornea connectivity with the right S1, right planum temporale, and right Heschl’s gyrus.
Conclusions
Proparacaine non-responders had greater S1-cornea functional connectivity in more regions brain-wide, including the left insula (associated with affective processing) and visual cortex. This is consistent with clinical reports that chronic ocular pain can be unaffected by local anesthetic eyedrops and may involve central sensitization. Responders showed S1-cornea connectivity in somatosensory networks, including S1, and S2. This suggests that different neural mechanisms of photophobia and ocular pain may be differentiable based on the response to pharmacological intervention at the level of the corneal afferents.
References
1.Choudhury A, Reyes N, Galor A, Mehra D, Felix E, Moulton EA. Clinical Neuroimaging of Photophobia in Individuals With Chronic Ocular Surface Pain. Am J Ophthalmol. 2023 Feb;246:20-30. doi: 10.1016/j.ajo.2022.09.020. Epub 2022 Oct 9. PMID: 36223850.
2.Moulton EA, Becerra L, Rosenthal P, Borsook D. An approach to localizing corneal pain representation in human primary somatosensory cortex. PLoS One. 2012;7(9):e44643. doi: 10.1371/journal.pone.0044643. Epub 2012 Sep 4. PMID: 22973463; PMCID: PMC3433421.
3.Reyes N, Huang JJ, Choudhury A, Pondelis N, Locatelli EV, Felix ER, Pattany PM, Galor A, Moulton EA. Botulinum toxin A decreases neural activity in pain-related brain regions in individuals with chronic ocular pain and photophobia. Front Neurosci. 2023 Jun 19;17:1202341. doi: 10.3389/fnins.2023.1202341. PMID: 37404468; PMCID: PMC10315909.
4.Reyes N, Huang JJ, Choudhury A, Pondelis N, Locatelli EVT, Hollinger R, Felix ER, Pattany PM, Galor A, Moulton EA. FL-41 Tint Reduces Activation of Neural Pathways of Photophobia in Patients with Chronic Ocular Pain. Am J Ophthalmol. 2023 Dec 14;259:172-184. doi: 10.1016/j.ajo.2023.12.004. Epub ahead of print. PMID: 38101593
Presenting Author
Priya Patel
Poster Authors
Priya Patel
BS, MS
Boston Children's Hospital
Lead Author
Nicholas Reyes
MD
The University of Miami Miller School of Medicine
Lead Author
Jacob Sperber
BS
Boston Children's Hospital, Harvard Medical School
Lead Author
Pradip Pattany
PhD
The University of Miami Miller School of Medicine
Lead Author
Anat Galor
MD
The University of Miami Miller School of Medicine
Lead Author
Elizabeth Felix
Univ of Miami, Miller School of Medicine
Lead Author
Scott Holmes
PhD
Boston Children's Hospital, Harvard Medical School
Lead Author
Eric Moulton
Boston Children's Hospital, Harvard Medical School
Lead Author
Topics
- Pain Imaging