Met-Enkephalin-Arg 6-Phe 7-like immunoreactive substances mediate electroacupuncture analgesia in the periaqueductal gray of the rabbit

Abstract

The present study was undertaken to investigate whether the C-terminal extended Met-enkephalin heptapeptide (Met-enkephalin-Arg 6-Phe 7, MEAP) played a role in mediating the analgesic effect of electroacupuncture in rabbits. MEAP and its degrading enzyme inhibitor captopril as well as antiserum against MEAP were injected into the periaqueductal gray (PAG) via a previously implanted cannula. Their effects on nociception were tested by the escape response latency (ERL) elicited by radiant heat applied on the skin of the snout. (1) Microinjection of MEAP (30–240 nmol) into PAG produced a dose-dependent analgesic effect which was 2.5 times more potent than Met-enkephalin (MEK) and 3 times less potent than morphine. The complete reversal of the analgesia elicited by 240 nmol of MEAP by a small dose of naloxone (0.1 mg/kg, i.v.) indicates that the effect of MEAP is mediated by naloxone sensitive opioid receptors. (2) In rabbits, a dose-dependent analgesia was elicited by an intra-PAG injection of captopril (60–240 nmol). A single dose of 240 nmol captopril increased ERL by more than 100%. This effect could be reversed by 30 nmol of naloxone injected into the same site, or by antiserum recognizing MEAP (1 μL, titer 1:1500) but not by antiserum recognizing MEK (1 μl, 1:8000) suggesting that captopril was able to protect MEAP from degradation. (3) Intra-PAG injection of 60 nmol of captopril significantly potentiated the after effect of electroacupuncture (EA) induced analgesia. This effect could be blocked either by 30 nmol (but not 7.5 nmol) of naloxone, or by 1 μl (but not 0.1 μl) of MEAP antiserum. These results suggest that MEAP may cause analgesia by acting in PAG, and could be operative in EA analgesia.