Involvement of spinal δ-opioid receptor subtypes in stress-induced antinociception caused by repeated exposure to forced walking stress in mice

We examined the effects of repeated exposure to forced walking stress for 6 hr once a day for 9 consecutive days on formalin-induced paw licking in mice. Stress-induced antinociception (SIA) was observed only in the late phase (from 10 to 30 min), but not in the early phase (from 0 to 10 min) of formalin-induced paw licking in mice. Naloxone (10 mg/kg), an opioid receptor antagonist, was effective in reducing the SIA induced by forced walking stress for 9 days. Intrathecal treatment with naltrindole, a selective δ-opioid receptor antagonist, 7-benzylidenenaltrexone, a selective δ 1 -opioid receptor antagonist or naltriben, a selective δ 2 -opioid receptor antagonist, attenuated the SIA. In contrast, intrathecal pretreatment with nor-binaltorphimine, κ-opioid receptor antagonist, had no significant effect on it. These results suggest that the repeated forced walking SIA is mediated by spinal δ 1 - and δ 2 -opioid receptors in mice.