ET-1 (100 ng, i.d. on dorsum of the hind paw) induced mechanical hyperalgesia (reading 1, 15 min post-administration) that was enhanced by repeat threshold intensity stimuli applied at the site of nociceptive testing (i.e. stimulus-dependent hyperalgesia).
A. Intravenous administration of methionine (1 mg/kg) or homocysteine (3 mg/kg), 30 min before ET-1, markedly attenuated the ET-1 hyperalgesia, and completely eliminated stimulus-dependent hyperalgesia.
B. Intravenous administration methionine (1 mg/kg) or homocysteine (3 mg/kg), 3 h before ET-1 did not affect ET-1 hyperalgesia. Stimulus-dependent hyperalgesia was completely eliminated by methionine but not by homocysteine at the 3 h pretreatment time point.
C. Intradermal administration methionine (1 μg) or homocysteine (5 μg) 30 min before ET-1 markedly attenuated ET-1 hyperalgesia, and completely eliminated stimulus-dependent hyperalgesia.
D. Intradermal administration methionine (1 μg) or homocysteine (5 μg) 3 h before ET-1 did not affect ET-1 hyperalgesia. Stimulus-dependent hyperalgesia was completely eliminated by methionine but enhanced by homocysteine, at the 3 h pretreatment time point.