Project: Research project

Project Details


Opioids are classically viewed as having analgesic actions with
little-to-no anti-inflammatory activity. It is generally recognized that
opioids produce analgesia through activation of receptors located in the
central nervous system (CNS) at both spinal and supraspinal levels.
However, recent studies indicate that opioids also act in the periphery to
suppress sensitized nociceptive afferent nerve fibers and to produce a
peripherally-mediated antinociception. These observations that opioids act
in inflamed tissue to produce antinociception suggest that they may also
act to alter the development of tissue inflammation. A possible anti-inflammatory action of opioids is supported by several
lines of evidence. For example, opioid receptors have been reported to be
present on peripheral afferent and sympathetic fibers, and leukocytes, all
of which are thought to be involved in inflammation. In addition,
peripheral effects of opioids on plasma extravasation have been
demonstrated using an animal preparation involving electrical stimulation
of the saphenous nerve. Furthermore, recent studies using actual models of
inflammation have demonstrated that opioids suppress edema, hyperthermia
and plasma extravasation, in parallel to their reduction of hyperalgesia.
These anti-inflammatory opioids are stereospecific, dose-related and
naltrexone-reversible [see preliminary results]. However, the opioid
receptor subtype mediating these anti-inflammatory effects and the
site/mechanism of action undetermined. This proposal will extend our knowledge in this area by characterizing the
receptor sub-type mediating the anti-inflammatory effects of opioids and
determining its mechanism of action. Specifically, the proposed studies
will evaluate the effects of opioids on carrageenan-induced edema,
hyperthermia, plasma extravasation and hyperalgesia. In addition, opioid
suppression of released levels of inflammatory mediators will be evaluated
using microdialysis probes implanted into the hindpaws of rats injected
with carrageenan. The proposed studies will: 1) determine the receptor
sub-type(s) mediating anti-inflammatory actions of opioids and their
location by comparing ED50 values of mu, delta and kappa selective opioids
after peripheral (ipl), systemic (ip) or central (icv) administration; 2)
determine whether the anti-inflammatory . action of opioids is due to
suppression of primary afferent nociceptor fiber activity; 3) determine
whether the anti-inflammatory action of opioids is due to suppression of
leukocyte activity; and 4) determine whether the anti-inflammatory action
of opioids is due to suppression of sympathetic fiber activity.
Effective start/end date3/15/922/28/94


  • National Institutes of Health: $70,000.00


  • Medicine(all)


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