Elsevier

Neuroscience

Volume 159, Issue 2, 17 March 2009, Pages 787-794
Neuroscience

Pain Mechanism
Ocular surface-evoked Fos-like immunoreactivity is enhanced in trigeminal subnucleus caudalis by prior exposure to endotoxin

https://doi.org/10.1016/j.neuroscience.2008.12.015Get rights and content

Abstract

Endotoxin-induced uveitis (EIU) is a common animal model for anterior uveitis in humans that causes long-term changes in trigeminal brain stem neurons. This study used c-fos immunohistochemistry to assess the effects of different routes of administration of endotoxin on activation of trigeminal brain stem neurons produced by ocular surface stimulation. A single dose of endotoxin (lipopolysaccharide (LPS)) given to male rats by systemic (i.p., 1 mg/kg) or intraocular (ivt, 20 μg) routes increased the number of Fos-positive neurons in rostral (trigeminal subnucleus interpolaris/subnucleus transition (Vi/Vc)) and caudal portions of trigeminal subnucleus caudalis (trigeminal subnucleus caudalis/upper cervical spinal cord transition (Vc/C1–2)) by 20% mustard oil (MO) applied to the ocular surface 7 days, but not at 2 days, after LPS compared with naïve rats. I.c.v. (20 μg) LPS did not affect MO-evoked Fos. To determine if the pattern of enhanced Fos expression after systemic LPS also depended on the nature of the ocular surface stimulus, additional groups received ocular stimulation by 10% histamine or dry eye conditions. Seven days, but not 2 days, after i.p. LPS both histamine- and dry eye–evoked Fos was increased at the Vi/Vc transition, while smaller effects were seen at other regions. These results suggested that EIU modulation of trigeminal brain stem neuron activity was mediated mainly by peripheral actions of LPS. Enhancement of Fos at the Vi/Vc region after MO, histamine and dry eye conditions supports the hypothesis that this region integrates innocuous as well as noxious sensory information, while more caudal portions of Vc process mainly nociceptive signals from the eye.

Section snippets

Experimental procedures

The experimental 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 and use of laboratory animals (Publications No. 99–158, revised 2002). All efforts were made to minimize the number of animals used for experiments and their suffering.

General effects of LPS

Naïve rats gained 6.1±1.3% and 21.5±5.4% of initial body weight by 2 and 7 days, respectively, over the course of the experimental period. Rats given systemic LPS had minor weight loss at 2 days (−3.3±1.5%, P>0.05) and a significant gain at 7 days (7.7±2.2%, P<0.01) compared with naïve rats. Rats given ivt injections of LPS also had minor weight loss by 2 days (0.3±0.8%, P>0.05) and gained weight at 7 days (5.3±2.7%, P<0.05) compared with naïve rats. By contrast, rats given i.c.v. LPS rats lost

Discussion

The main finding of this study was that systemic or intraocular administration of LPS enhanced Fos-LI expression in multiple TSNC regions after noxious chemical stimulation of the ocular surface in a time-dependent manner, while intracerebral LPS had only minor effects. Noxious sensory stimulation of the ocular surface by MO significantly increased Fos-LI in the ViVcvl transition and Vc/C1–2 junction regions, responses that were further enhanced by 7 days, but not 2 days, after systemic or

Acknowledgments

This was supported by NIH grant NS26137. The authors wish to thank J. Cioffi for excellent technical assistance.

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