Negative modulation of spinal κ-opioid receptor-mediated antinociception by the µ-opioid receptor at selective doses of (-)-pentazocine.

Abstract:

:The mixed-action κ-opioid receptor (KOR) agonist, pentazocine, binds to both KOR and the µ-opioid receptor (MOR). Racemic (±)-pentazocine and (-)-pentazocine, each administered systemically, have been shown to produce antinociception in various animal models. In contrast, racemic (±)-pentazocine failed to produce antinociception when administered intrathecally (i.t.). However, whether spinal activation of KOR and MOR by (-)-pentazocine produces antinociception and the relative contribution of KOR and MOR in mediating antinociception remain unknown. Hence, we investigated whether i.t. (-)-pentazocine produces dose-dependent modulation of acute thermal nociception. Drugs were administered intrathecally in Sprague-Dawley rats and tail flick latency was recorded. Pentazocine produced a significant antinociceptive effect that was mediated by KOR and/or MOR at differential doses. MOR blockade restored the antinociceptive effect of an ineffective dose and prolonged the duration of an effective dose of pentazocine. Hence, spinal KOR and MOR mediated the effect of pentazocine. This study provides evidence that spinal MOR negatively modulates the KOR-mediated antinociceptive effect of i.t. pentazocine.

journal_name

Neuroreport

journal_title

Neuroreport

authors

Robinson DL Jr,Nag S,Mokha SS

doi

10.1097/WNR.0000000000001043

subject

Has Abstract

pub_date

2018-07-04 00:00:00

pages

852-855

issue

10

eissn

0959-4965

issn

1473-558X

journal_volume

29

pub_type

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