Oculofacial Pain: Corneal Nerve Damage Leading to Pain Beyond the Eye

Perry Rosenthal, David Borsook, Eric A Moulton, Perry Rosenthal, David Borsook, Eric A Moulton

Abstract

The cornea is supplied principally by the ophthalmic branch of the trigeminal nerve and is the most densely innervated organ in the human body. Under normal conditions, the corneal nerve terminals incorporate sensors that monitor the thickness and integrity of the tear film, which are essential for meaningful vision. A disrupted tear film or direct noxious stimulation of these corneal nerves can produce discomfort or pain limited to the affected surface. Damage to these nerves can sometimes lead to a chronic neuropathic condition, where pain persists months following the initial insult, long after the nerves appear to have healed in the cornea itself following treatment. Neuropathic pain appears to persist indefinitely in a few patients.

Figures

Figure
Figure
Trigeminal convergence pathway for oculofacial pain. Temperature, mechanosensitive, and polymodal nociceptors transduce noxious input from acute injury or inflammation into neural signals. Innervation of the cornea supplies afferents through branches of the ophthalmic division of the trigeminal nerve. These first-order neurons converge with afferent inputs from the other two divisions of the trigeminal nerve (maxillary and mandibular) and are somatotopically organized within the trigeminal ganglion. The neuronal bodies of the trigeminal nerve, located in the ganglion, have central projections that synapse in the trigeminal nucleus. Second-order neurons cross over in their ascending pathway (trigeminothalamic tract) to nuclei within the thalamus (e.g., ventroposteriormedial thalamus). From here, third-order neurons project to the primary somatosensory cortex where the cornea is functionally represented. The boxes below show referred pain (left) to the cornea from orofacial somatic and visceral structures and (right) to orofacial viscera from the cornea and skin. Such convergence may occur within the central nervous system, potentially involving the trigeminal nucleus and/or thalamus.

References

    1. Kalangara JP,, Galor A,, Levitt RC,, Felix ER,, Alegret R,, Sarantopoulos CD. Burning eye syndrome: do neuropathic pain mechanisms underlie chronic dry eye? Pain Med. 2016; 17: 746–755.
    1. Galor A,, Levitt RC,, Felix ER,, Martin ER,, Sarantopoulos CD. Neuropathic ocular pain: an important yet underevaluated feature of dry eye. Eye (Lond). 2015; 29: 301–312.
    1. Galor A,, Zlotcavitch L,, Walter SD,, et al. Dry eye symptom severity and persistence are associated with symptoms of neuropathic pain. Br J Ophthalmol. 2015; 99: 665–668.
    1. Rosenthal P,, Borsook D. Ocular neuropathic pain. Br J Ophthalmol. 2016; 100: 128–134.
    1. Rosenthal P,, Borsook D. The corneal pain system. Part I: the missing piece of the dry eye puzzle. Ocul Surf. 2012; 10: 2–14.
    1. Bower KS,, Sia RK,, Ryan DS,, Mines MJ,, Dartt DA. Chronic dry eye in photorefractive keratectomy and laser in situ keratomileusis: manifestations, incidence, and predictive factors. J Cataract Refract Surg. 2015; 41: 2624–2634.
    1. Taneri S,, Oehler S,, Asimellis G,, Kanellopoulos AJ. Influence of corneal cross-linking for keratoconus on several objective parameters of dry eye. J Refract Surg. 2013; 29: 612–616.
    1. Han KE,, Yoon SC,, Ahn JM,, et al. Evaluation of dry eye and meibomian gland dysfunction after cataract surgery. Am J Ophthalmol. 2014; 157: 1144–1150.e1.
    1. Kosker M,, Duman F,, Suri K,, Hammersmith KM,, Nagra PK,, Rapuano CJ. Long-term results of keratoplasty in patients with herpes zoster ophthalmicus. Cornea. 2013; 32: 982–986.
    1. Kehlet H,, Jensen TS,, Woolf CJ. Persistent postsurgical pain: risk factors and prevention. Lancet. 2006; 367: 1618–1625.
    1. Kinard KI,, Smith AG,, Singleton JR,, et al. Chronic migraine is associated with reduced corneal nerve fiber density and symptoms of dry eye. Headache. 2015; 55: 543–549.
    1. Goadsby PJ,, Charbit AR,, Andreou AP,, Akerman S,, Holland PR. Neurobiology of migraine. Neuroscience. 2009; 161: 327–341.
    1. Digre KB,, Brennan KC. Shedding light on photophobia. J Neuroophthalmol. 2012; 32: 68–81.
    1. Dolgonos S,, Ayyala H,, Evinger C. Light-induced trigeminal sensitization without central visual pathways: another mechanism for photophobia. Invest Ophthalmol Vis Sci. 2011; 52: 7852–7858.
    1. Okamoto K,, Tashiro A,, Chang Z,, Bereiter DA. Bright light activates a trigeminal nociceptive pathway. Pain. 2010; 149: 235–242.
    1. Moulton EA,, Becerra L,, Borsook D. An fMRI case report of photophobia: activation of the trigeminal nociceptive pathway. Pain. 2009; 145: 358–363.
    1. Moulton EA,, Becerra L,, Rosenthal P,, Borsook D. An approach to localizing corneal pain representation in human primary somatosensory cortex. PLoS One. 2012; 7: .
    1. Siqueira SR,, Siviero M,, Alvarez FK,, Teixeira MJ,, Siqueira JT. Quantitative sensory testing in trigeminal traumatic neuropathic pain and persistent idiopathic facial pain. Arq Neuropsiquiatr. 2013; 71: 174–179.
    1. Falace DA,, Reid K,, Rayens MK. The influence of deep (odontogenic) pain intensity, quality and duration on the incidence and characteristics of referred orofacial pain. J Orofac Pain. 1996; 10: 232–239.
    1. Drummond PD. Photophobia and autonomic responses to facial pain in migraine. Brain J Neurol. 1997; 120 (pt 10): 1857–1864.
    1. Shibuta K,, Suzuki I,, Shinoda M,, et al. Organization of hyperactive microglial cells in trigeminal spinal subnucleus caudalis and upper cervical spinal cord associated with orofacial neuropathic pain. Brain Res. 2012; 1451: 74–86.
    1. Sikandar S,, Dickenson AH. Visceral pain: the ins and outs the ups and downs. Curr Opin Support Palliat Care. 2012; 6: 17–26.
    1. Li Y,, Dorsi MJ,, Meyer RA,, Belzberg AJ. Mechanical hyperalgesia after an L5 spinal nerve lesion in the rat is not dependent on input from injured nerve fibers. Pain. 2000; 85: 493–502.
    1. Sang CN,, Gracely RH,, Max MB,, Bennett GJ. Capsaicin-evoked mechanical allodynia and hyperalgesia cross nerve territories. Evidence for a central mechanism. Anesthesiology. 1996; 85: 491–496.
    1. Sessle BJ. Neural mechanisms and pathways in craniofacial pain. Can J Neurol Sci. 1999; 26 (suppl 3): S7–S11.
    1. Sessle BJ,, Hu JW,, Amano N,, Zhong G. Convergence of cutaneous, tooth pulp, visceral neck and muscle afferents onto nociceptive and non-nociceptive neurones in trigeminal subnucleus caudalis (medullary dorsal horn) and its implications for referred pain. Pain. 1986; 27: 219–235.
    1. Ugurlu S,, Bartley GB,, Otley CC,, Baratz KH. Factitious disease of periocular and facial skin. Am J Ophthalmol. 1999; 127: 196–201.
    1. Sandrini G,, Alfonsi E,, Ruiz L,, et al. Impairment of corneal pain perception in cluster headache. Pain. 1991; 47: 299–304.
    1. Belmonte C,, Acosta MC,, Merayo-Lloves J,, Gallar J. What causes eye pain? Curr Ophthalmol Rep. 2015; 3: 111–121.

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