The kappa opioid agonist GR89696 blocks hyperalgesia and allodynia in rat models of peripheral neuritis and neuropathy

Previous work demonstrated that, in rats, intrathecal GR89 696, a putative kappa-2 opioid receptor agonist, inhibited hyperalgesia to noxious heat in an inflamed hind paw (anti-hyperalgesic effect). Non-inflamed paws were not influenced by kappa-2 receptor activation. The question addressed in this study was whether GR89 696 was as effective in blocking hyperalgesia and al lodynia in nerve injury models as it was in the inflammation model. GR89 69 6 (6 nmoles, i.t.) completely reversed the hyperalgesia and allodynia obser ved in both the neuropathy and neuritis models in all sensory tests. Howeve r, it did not alter sensory function in non-injured limbs nor in sham opera ted animals. Naloxone (1 mg/kg, i.p.) reversed the anti-hyperalgesic and an ti-allodynic effects of GR89 696. The mu agonist DAMGO (6 nmoles, i.t.) and the kappa-1 agonist U69 593 (100 nmoles, i.t.) only partially reversed hyp eralgesia and allodynia. These findings suggest that kappa-2 opioid recepto rs may be a useful target for the pharmacological control of hyperalgesia a nd allodynia. (C) 1999 Published by Elsevier Science B.V.