Chronic inflammatory pain prevents tolerance to the antinociceptive effect of morphine microinjected into the ventrolateral periaqueductal gray of the rat

Melissa L Mehalick; Susan L Ingram; Sue A Aicher; Michael M Morgan

doi:10.1016/j.jpain.2013.08.003

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Chronic inflammatory pain prevents tolerance to the antinociceptive effect of morphine microinjected into the ventrolateral periaqueductal gray of the rat

Journal article

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Chronic inflammatory pain prevents tolerance to the antinociceptive effect of morphine microinjected into the ventrolateral periaqueductal gray of the rat

Melissa L Mehalick, Susan L Ingram, Sue A Aicher and Michael M Morgan

The journal of pain, Vol.14(12), pp.1601-1610

12/2013

DOI: https://doi.org/10.1016/j.jpain.2013.08.003

Handle:

https://hdl.handle.net/2376/104683

PMCID: PMC3876795

PMID: 24161274

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https://doi.org/10.1016/j.jpain.2013.08.003View

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Abstract

Inflammation - pathology

Chronic Pain - drug therapy

Microinjections - methods

Periaqueductal Gray - drug effects

Drug Tolerance - physiology

Rats

Male

Pain Measurement - drug effects

Treatment Outcome

Chronic Pain - pathology

Rats, Sprague-Dawley

Pain Measurement - methods

Animals

Analgesics, Opioid - administration & dosage

Inflammation - drug therapy

Periaqueductal Gray - physiology

Morphine - administration & dosage

The ventrolateral periaqueductal gray (vlPAG) contributes to morphine antinociception and tolerance. Chronic inflammatory pain causes changes within the PAG that are expected to enhance morphine tolerance. This hypothesis was tested by assessing antinociception and tolerance following repeated microinjections of morphine into the vlPAG of rats with chronic inflammatory pain. Microinjection of morphine into the vlPAG reversed the allodynia caused by intraplantar administration of complete Freund's adjuvant and produced antinociception on the hot plate test. Although there was a gradual decrease in morphine antinociception with repeated testing, there was no evidence of tolerance when morphine- and saline-treated rats with hind paw inflammation were tested with cumulative doses of morphine. In contrast, repeated morphine injections into the vlPAG caused a rightward shift in the morphine dose-response curve in rats without hind paw inflammation, as would be expected with the development of tolerance. The lack of tolerance in complete Freund's adjuvant-treated rats was evident whether rats were exposed to repeated behavioral testing or not (experiment 2) and whether they were treated with 4 or 8 prior microinjections of morphine into the vlPAG (experiment 3). These data demonstrate that chronic inflammatory pain does not disrupt the antinociceptive effect of microinjecting morphine into the vlPAG, but it does disrupt the development of tolerance. The present data show that induction of chronic inflammatory pain does not disrupt the antinociceptive effect of microinjecting morphine into the vlPAG, but it does attenuate the development of tolerance. This finding indicates that tolerance to opioids in rats with inflammatory pain is mediated by structures other than the vlPAG.

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Title: Chronic inflammatory pain prevents tolerance to the antinociceptive effect of morphine microinjected into the ventrolateral periaqueductal gray of the rat
Creators: Melissa L Mehalick - Department of Psychology, Washington State University Vancouver, Vancouver, Washington. Electronic address: mmehalick@wsu.edu
Susan L Ingram
Sue A Aicher
Michael M Morgan
Publication Details: The journal of pain, Vol.14(12), pp.1601-1610
Academic Unit: Psychology, Department of
Publisher: United States
Grant note: R01 DA027625 / NIDA NIH HHS
Identifiers: 99900547078101842
Language: English
Resource Type: Journal article