Does the antihyperalgesic disruptor of endothelial cells, octoxynol-9, alter nociceptor function?

Abstract

The vasoactive mediator, endothelin-1, elicits a novel form of hyperalgesia, stimulation-dependent hyperalgesia. Acting on its cognate receptor on the vascular endothelial cell, endothelin-1 produces a state in which mechanical stimulation now elicits release of pronociceptive mediators from endothelium that, in turn, acts at receptors on sensory neurons. The only evidence that octoxynol-9, a surface-active agent that attenuates both endothelial cell function and stimulus-dependent hyperalgesia, does not affect nociceptors is indirect (i.e., octoxynol-9 treatment did not affect behavioral nociceptive threshold or hyperalgesia induced by agents that act directly on nociceptors). To help address the question of whether the attenuation of stimulation-dependent hyperalgesia by octoxynol-9 treatment is due to alteration of nociceptor function, we used in vivo single-fiber electrophysiological recordings. Consistent with our previous behavioral observations, we observed no significant effect of octoxynol-9 on mechanical threshold in nociceptors, their response to sustained suprathreshold mechanical stimulation, conduction velocity, and change in mechanical threshold in response to the direct-acting hyperalgesic agent, PGE2. Although octoxynol-9 did not produce a biologically meaningful change in parameters of nociceptor function, we cannot exclude the possibility of a type II error. However, our data provide preliminary evidence of no effect of octoxynol-9 on nociceptors and are consistent with the suggestion that the primary action of octoxynol-9 in our studies is due to its action on the endothelium.

• Authors: Xiaojie Chen, Paul G Green, Jon D Levine
• Journal: Journal of neurophysiology (J Neurophysiol) Vol. 112 Issue 2 Pg. 463-6 (Jul 15 2014) ISSN: 1522-1598 [Electronic] United States
• PMID: 24790171 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2014 the American Physiological Society.

Chemical References

• Surface-Active Agents
• Octoxynol

Topics

• Action Potentials
• Animals
• Endothelial Cells (drug effects)
• Hyperalgesia (metabolism)
• Male
• Nociception
• Nociceptors (drug effects, physiology)
• Octoxynol (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Sensory Thresholds
• Surface-Active Agents (pharmacology)