ORPHANIN FQ or nociceptin (OFQ/N1-17) is a recently discovered peptide
which, upon intracerebroventricular administration, reverses opioid-m
ediated analgesias. OFQ/N1-17 terminals are located in the periaqueduc
tal gray (PAG), a structure known to be involved in pain modulation, s
uggesting that the functional anti-opioid effects of OFQ/N1-17 are med
iated by PAG neurons. To test this, subsequent microinjections of morp
hine or kainic acid and OFQ/N1-17 were made into the PAG of awake rats
. Administration of OFQ/N1-17 attenuated the tail flick inhibition pro
duced by both morphine and kainic acid microinjection. OFQ/N1-17 atten
uation of antinociception produced by a neuroexcitant indicates that O
FQ/N1-17 reverses opioid antinociception by inhibiting PAG output neur
ons.