Abstract
Recent studies have suggested that prolonged exposure to morphine results in the development of paradoxical, abnormal enhanced pain. It has also been suggested that this enhanced pain state may be interpreted as antinociceptive tolerance. Although the precise mechanisms that drive opioid-induced abnormal pain are not well known, considerable evidence suggests that this state may be supported by enhanced, stimulus-evoked excitatory transmission. We hypothesized that blockade of L-type calcium channels, which are critical for excitatory neurotransmitter release, would alter the development of opioid-induced hyperalgesia and antinociceptive tolerance. Male, Swiss-Webster mice received twice-daily intrathecal injections of morphine (10 microg) alone or in combination with amlodipine (10 microg) for 8 days. Mice receiving repeated morphine injections developed enhanced responses to tactile and thermal stimuli. These hypersensitivities were prevented by the coadministration of the putative selective L-type calcium channel blocker amlodipine. Moreover, mice receiving morphine for 8 days demonstrated a significant rightward shift of the morphine antinociceptive dose-response curve, indicative of antinociceptive tolerance, whereas those that also received amlodipine along with morphine did not demonstrate tolerance. These results suggest that blockade of the L-type calcium channels with amlodipine prevented opioid-induced hyperalgesia and the expression of antinociceptive tolerance to spinal morphine, presumably by reducing stimulus-induced excitatory neurotransmitter release.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.