Evidence is presented that the recently discovered endogenous mu-selective
agonist, endomorphin-2, is localized in primary sensory afferents. Endomorp
hin-2-like immunoreactivity was found to be colocalized in a subset of subs
tance P- and mu opiate receptor-containing fibers in the superficial lamina
e of the spinal cord and spinal trigeminal nucleus. Disruption of primary s
ensory afferents by mechanical (deafferentation by dorsal rhizotomy) or che
mical (exposure to the primary afferent neurotoxin, capsaicin) methods virt
ually abolished endomorphin-2-like immunoreactivity in the dorsal horn. The
se results indicate that endomorphin-2 is present in primary afferent fiber
s where it can serve as the endogenous ligand for pre- and postsynaptic mu
receptors and as a major modulator of pain perception. (C) 1998 Elsevier Sc
ience Inc.