Elsevier

Neuroscience

Volume 169, Issue 1, 11 August 2010, Pages 455-462
Neuroscience

Pain Mechanisms and Sensory Neuroscience
Research Paper
Behavioral and neurophysiological correlates of nociception in an animal model of photokeratitis

https://doi.org/10.1016/j.neuroscience.2010.04.034Get rights and content

Abstract

Ocular exposure to ultraviolet irradiation (UVR) induces photokeratitis, a common environmental concern that inflames ocular tissues and causes pain. The central neural mechanisms that contribute to the sensory aspects of photokeratitis after UVR are not known. In awake male rats, ocular surface application of hypertonic saline evoked eye wipe behavior that was enhanced 2–3 days after UVR and returned to control levels by 7 days. Similarly, under isoflurane anesthesia, hypertonic saline-evoked activity of ocular neurons in superficial laminae at the trigeminal subnucleus caudalis/cervical (Vc/C1) region was enhanced 2 days, but not 7 days, after UVR. By contrast, the response of neurons at the interpolaris/caudalis (Vi/Vc) transition region to hypertonic saline was not affected by UVR. The background activity and convergent cutaneous receptive field areas of Vc/C1 or Vi/Vc neurons were not affected by UVR. Aqueous humor protein levels were elevated 2 and 7 days after UVR. UVR enhanced nociceptive behavior, after a latent period, with a time course similar to that of ocular neurons in superficial laminae at the Vc/C1 region. The Vc/C1 region plays a key role in primary hyperalgesia induced by UVR, whereas the Vi/Vc region likely mediates other aspects of ocular function.

Section snippets

Experimental procedures

The animal protocols were approved by the Institutional Animal Care and Use Committee of the University of Minnesota and conformed to the established guidelines set by The National Institutes of Health guide for the care of laboratory animals (PHS Law 99–158, revised 2002).

General effects of UVR

There were no visible signs of ocular inflammation immediately and for several hours after UVR regardless of intensity. By 1 day after moderate or high intensity UVR (200 or 300 mJ/cm2) the irradiated eye displayed a dilated pupil and signs of inflammation such as hyperemia of the sclera and corneal opacities that gradually diminished over 7 days. After low intensity UVR (100 mJ/cm2), the pupil was dilated slightly for 1–2 days, with some hyperemia of the sclera and corneal opacity that

Discussion

These data indicated that acute exposure of the eye to UVR produced, after a 1 day latent period, a transient increase in ocular-specific nociceptive behavior evoked by hypertonic saline applied to the ocular surface. The time course for UVR-induced changes in behavior matched well the increase in responsiveness of neurons in superficial laminae at the Vc/C1 region to hypertonic saline. By contrast, although ocular neurons at the Vi/Vc transition region, located 4–5 mm rostral to the Vc/C1

Acknowledgments

The authors thank Randall Thompson for excellent technical assistance. This work was supported in part by a grant from the NIH (NS26137).

References (53)

  • R. Farazifard et al.

    Eye-wiping test: a sensitive animal model for acute trigeminal pain studies

    Brain Res Brain Res Protoc

    (2005)
  • R.T. Hoffmann et al.

    Time course of UVA- and UVB-induced inflammation and hyperalgesia in human skin

    Eur J Pain

    (1999)
  • W. Koppert et al.

    Mechanically induced axon reflex and hyperalgesia in human UV-B burn are reduced by systemic lidocaine

    Eur J Pain

    (2004)
  • Y. Matsumura et al.

    Toxic effects of ultraviolet radiation on the skin

    Toxicol Appl Pharmacol

    (2004)
  • A.J. Rozsa et al.

    Density and organization of free nerve endings in the corneal epithelium of the rabbit

    Pain

    (1982)
  • R. Rukwied et al.

    Nociceptor sensitization to mechanical and thermal stimuli in pig skin in vivo

    Eur J Pain

    (2008)
  • L. Urban et al.

    Activity of deep dorsal horn neurons in the anaesthetized rat during hyperalgesia of the hindpaw induced by ultraviolet irradiation

    Neuroscience

    (1993)
  • H. Wenk et al.

    Silver nitrate cauterization: characterization of a new model of corneal inflammation and hyperalgesia in the rat

    Pain

    (2003)
  • J.N. Baraniuk et al.

    Hypertonic saline nasal provocation stimulates nociceptive nerves, substance P release, and glandular mucous exocytosis in normal humans

    Am J Respir Crit Care Med

    (1999)
  • C. Belmonte et al.

    Excitation by irritant chemical substances of sensory afferent units in the cat's cornea

    J Physiol

    (1991)
  • D.A. Bereiter et al.

    Trigeminal mechanisms of nociception: peripheral and brainstem organization

  • D.A. Bereiter et al.

    Endotoxin-induced uveitis causes long-term changes in trigeminal subnucleus caudalis neurons

    J Neurophysiol

    (2005)
  • J.P. Bergmanson

    Corneal damage in photokeratitis—why is it so painful?

    Optom Vis Sci

    (1990)
  • J. Cejkova et al.

    UV rays, the prooxidant/antioxidant imbalance in the cornea and oxidative eye damage

    Physiol Res

    (2004)
  • C.Y. Chiang et al.

    Central sensitization of nociceptive neurons in trigeminal subnucleus orlais depends on the integrity of subnucleus caudalis

    J Neurophysiol

    (2002)
  • A.J. Cook et al.

    Dynamic receptive field plasticity in rat spinal cord dorsal horn following C-primary afferent input

    Nature

    (1987)
  • Cited by (37)

    • Pharmacotherapy of dry eye disease and ocular pain

      2022, Handbook of Basic and Clinical Ocular Pharmacology and Therapeutics
    • Corneal pain and experimental model development

      2019, Progress in Retinal and Eye Research
    • Magnesium sulfate reduces formalin-induced orofacial pain in rats with normal magnesium serum levels

      2018, Pharmacological Reports
      Citation Excerpt :

      About 26% of the population is affected by some form of orofacial pain [1], most of which are dental-related, with over 5% of instances that are chronic [2]. Nondental forms of pain which specifically affect the trigeminal nerve include trigeminal neuralgia, migraine, temporomandibular disorders, burning mouth syndrome [3–5], eye pain [6], and salivary gland pain [7]. Following substantial injury to trigeminal nerve branches, chronic pain develops in about 3–5% of patients [8].

    View all citing articles on Scopus
    View full text