The kappa opioid agonist GR89,696 blocks hyperalgesia and allodynia in rat models of peripheral neuritis and neuropathy.

Previous work demonstrated that, in rats, intrathecal GR89696, 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 GR89696 was as effective in blocking hyperalgesia and allodynia in nerve injury models as it was in the inflammation model. GR89696 (6 nmoles, i.t.) completely reversed the hyperalgesia and allodynia observed in both the neuropathy and neuritis models in all sensory tests. However, it did not alter sensory function in non-injured limbs nor in sham operated animals. Naloxone (1 mg/kg, i.p.) reversed the anti-hyperalgesic and anti-allodynic effects of GR89696. The mu agonist DAMGO (6 nmoles, i.t.) and the kappa-1 agonist U69593 (100 nmoles, i.t.) only partially reversed hyperalgesia and allodynia. These findings suggest that kappa-2 opioid receptors may be a useful target for the pharmacological control of hyperalgesia and allodynia.