Opioids are widely used in the treatment of various types of
pain and hyperalgesic states. However, opioid related side effects
are well known and are representing a great challenge in
using these drugs for the management of pain. A combined use
of opioids with nonsteroidal anti-inflammatory drugs
(NSAlDs) has been advocated in clinical practice to potentiate
each other analgesic effect and to reduce the dose and related
side effects of both drugs. Several studies on animal and human
models have shown that such combination provides greater efficacy
in pain relief. Reducing the doses of opioids used, due to
the presence of N'SAIDs, ultimately reduces potential for side
effects. It is unclear whether NSA1Ds induces its opioid analgesic
potentiating effect through inhibition of COX1 or COX2
enzymes. Both isoforms contribute to the inflammatory process,
but COX2 is of considerable therapeutic interest as its induction,
results in an enhanced formation of prostaglandins,
during acute as well as chronic i eflammation. It g enerally a
ssumed t hat N SAIDs a nti-inflammatory and analgesic activity
is mediated via COX2 inhibition, in contrast, it has been reported
that the potencies of various NSA1Ds to potentiate opioid
induced presynaptic inhibitory effect nearly matched their
inhibitory potencies at COX1. The present study was designed
to study the effect of co-administration of the non selective
COX inhibitor, indomethacin or diclofenac with pentazocine on
pain relief and to compare it with the effect of its coadministralion
with the selective COX2 inhibitors, rofecoxib and m eloxicam.
T ail flick and hot p late a ssays w ere u sal a s m odds o
f central nociception. Non selective COX inhibitors, indomethacin
and diclofenac potentiated the antinoceceptive effect of the
opioid agonist pentazocine, an effect that was abolished by naloxone.
The selective COX2 inhibitors, rofecoxib and meloxicam
failed to modify the analgesic effect of pentazocine. These
results suggest that analgesia potentiating effect of NSAIDs is
mediated through inhibition of COXI rather COX2 enzyme.
The finding support a novel therapeutic intervention by which
reduced doses of opioids can be used in the presence of
NSAIDs that act preferentially on COX1 to produce effective
pain relief with reduced side effects. |
