The neuroanatomy of the endomorphins
Description
The endomorphins are endogenous peptides; that have high affinity and selectivity for the mu opiate receptor and potent analgesic activity. The distributions of endomorphin 1 (Tyr-Pro-Trp-Phe-NH2, EM1) and endomorphin 2 (Tyr-Pro-Phe-Phe-NH2, EM2) in the rat central nervous system (CNS) were determined by immunocytochemistry with two antisera, each demonstrating clear preference for the target antigen Evidence is presented that EM2 is localized in primary sensory afferents. EM2-like immunoreactivity was found in a continuous column in the superficial laminae of the spinal cord dorsal horn and nucleus of the spinal trigeminal tract. EM2-like immunoreactivity was colocalized in a subset of substance P- and mu opiate receptor (MOR)-containing fibers in these regions. Disruption of primary sensory afferents; by mechanical (deafferentation by dorsal rhizotomy) or chemical (exposure to the C-fiber toxin, capsaicin) methods virtually abolished EM2-like immunoreactivity in the dorsal horn. These results indicate that EM2 is present in primary afferent fibers where it can serve as the endogenous ligand for pre- and post-synaptic MOR and as a major modulator of pain perception Perikarya expressing EM2-like immunoreactivity were present in the posterior hypothalamus, whereas those expressing EM1-like immunoreactivity were present in both the posterior hypothalamus and the nucleus of the solitary tract (NTS). EM1-like immunoreactivity was more widely and densely distributed throughout the brain than EM2 like immunoreactivity, whereas EM2-like immunoreactivity was more prevalent in the spinal cord than EM1-like immunoreactivity. The greatest density of EMI-like immunoreactive (EM1L-IR) fibers was detected in the parabrachial nucleus and the NTS. The greatest density of EM2-like immunoreactive (EM2L-IR) fibers was detected in the superficial laminae of the spinal cord dorsal horn and the nucleus of the spinal trigeminal tract. The overall pattern of immunoreactivities was similar in rat, mouse, and guinea pig, but some differences were observed. In many but not in all locations, immunoreactive fibers were prominently present in regions in which MOR are concentrated. The neuroanatomical results suggest that endomorphins participate in modulating nociceptive and autonomic nervous system processes and responsiveness to stress