Selective ablation of mu-opioid receptor expressing neurons in the rostral ventromedial medulla attenuates stress-induced mechanical hypersensitivity.

Abstract

AIMS:

Chronic stress-related conditions are often associated with stress-induced hyperalgesia. However, the neural circuitry responsible for producing stress-induced hyperalgesia is not well characterized. The aim of this study was to determine the contribution of mu-opioid expressing brainstem neurons to the expression of stress-induced hyperalgesia.

MAIN METHODS:

The present study utilized a model of stress-induced mechanical hypersensitivity that involved application of repeated, light tactile whisker pad stimulation (WPS) in rats. Repeated WPS (10 applications/session, 4 sessions/h in 1 day, sessions on days 1-5 and 8-12) increased defensive-aggressive and hypervigilant behaviors, and produced hypersensitivity to tactile stimulation of the hind paw. In order to test the possible involvement of mu-opioid receptor expressing neurons in the rostral ventral medulla (RVM) to this response, rats received RVM microinjections of the toxin conjugate dermorphin-saporin or its control, saporin. Fourteen days later rats underwent either WPS or sham conditioning.

KEY FINDINGS:

Repeated WPS produced defensive-aggressive behaviors directed towards the stimulus and mechanical hypersensitivity of the hind paw that persisted for up to 2 weeks after the final WPS session. Dermorphin-saporin, but not saporin, microinjections prevented the development of hind paw mechanical hypersensitivity, but did not affect the defensive-aggressive behaviors.

SIGNIFICANCE:

The finding that chronic stress produces mechanical hypersensitivity through circuitry that involves the RVM provides a potential neurobiological basis for the complex interaction between chronic stress and pain.

• Authors: Jacques Reynolds, Edward J Bilsky, Ian D Meng
• Journal: Life sciences (Life Sci) Vol. 89 Issue 9-10 Pg. 313-9 (Aug 29 2011) ISSN: 1879-0631 [Electronic] Netherlands
• PMID: 21763327 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2011. Published by Elsevier Inc.

Chemical References

• Opioid Peptides
• Receptors, Opioid, mu
• Ribosome Inactivating Proteins, Type 1
• dermorphin-saporin
• Saporins

Topics

• Animals
• Behavior, Animal (drug effects, physiology)
• Brain Mapping
• Hyperalgesia (metabolism, prevention & control, psychology)
• Male
• Medulla Oblongata (drug effects, metabolism, pathology)
• Microinjections
• Neurons (drug effects, metabolism)
• Opioid Peptides (administration & dosage, pharmacology)
• Physical Stimulation
• Rats
• Rats, Sprague-Dawley
• Receptors, Opioid, mu (antagonists & inhibitors, biosynthesis)
• Ribosome Inactivating Proteins, Type 1 (administration & dosage, pharmacology)
• Saporins
• Stress, Psychological (metabolism, psychology)
• Touch
• Vibrissae