Controversy persists in relation to the
analgesic efficacy of
opioids in
neuropathic pain. In the present study the effects of acute, subcutaneous administration of the
mu-opioid receptor agonists
morphine,
methadone and
codeine were examined in rat models of peripheral and central
neuropathic pain. In the spared nerve injury (SNI) and chronic constriction injury (CCI) models of peripheral
neuropathic pain, both
morphine (6mg/kg) and
methadone (3mg/kg) attenuated
mechanical allodynia,
mechanical hyperalgesia and cold
allodynia for up to 1.5h post-injection (P<0.05);
codeine (30mg/kg) minimally alleviated mechanical
hypersensitivity in SNI, but not CCI rats. When administered to rats with photochemically-induced
spinal cord injury (SCI),
morphine (2 and 6mg/kg) and
methadone (0.5-3mg/kg) robustly attenuated mechanical and cold
allodynia for at least 2h post-injection (P<0.05).
Codeine (10 and 30mg/kg) also attenuated mechanical and cold
allodynia in this model for at least 3h after injection. The magnitude of
opioid-mediated antinociception was similar between SNI, SCI and non-injured rats as measured in the tail flick test. At antinociceptive doses, no motor impairment as determined by the rotarod test was observed. The therapeutic window (based on antiallodynia versus
ataxia) obtained for
codeine, was vastly superior to that obtained with
morphine or
methadone in SNI and SCI rats. Furthermore, the therapeutic window for
codeine in SCI rats was 4-fold greater than in SNI rats. Our results further support the efficacy of
mu-opioid receptor agonists in alleviating signs of
neuropathic pain in animal models of peripheral and especially central nerve injury.