Plantar incision in rat generates spontaneous
pain behaviour. The
opioid drug,
morphine used to treat
postsurgical pain produces tolerance after long-term administration.
Loperamide, a potent mu-
opioid agonist, has documented
analgesic action in various
pain conditions. However,
loperamide analgesia and associated tolerance following continuous spinal administration in
postsurgical pain has not been reported. Chronic
spinal infusion of drugs was achieved using intrathecal
catheters connected to osmotic minipump. Coinciding with the onset of
spinal infusion of
loperamide or
morphine, rats were subjected to plantar incision.
Pain-related behaviour was assessed by Hargreaves apparatus (
thermal hyperalgesia) and von Frey filaments (
mechanical allodynia).
Morphine and
loperamide (0.5, 1 and 2 microL/h) induced
analgesia was observed until 7th day post-plantar incision in Sprague-Dawley rats.
Morphine and
loperamide produced dose-dependent
analgesia.
Loperamide, in the highest dose, produced
analgesia till 7th day. However, the highest dose of
morphine produced inhibition of
thermal hyperalgesia till 5th day and
mechanical allodynia only till 3rd day post-plantar incision.
Morphine and
loperamide produced
analgesia in
postsurgical pain, which may be mediated through different mechanisms. Longer duration of
analgesia with
loperamide could probably be due sustained blockade of
calcium channels.