Corticotropin-releasing factor, urocortin 1, and their receptors in the mouse spinal cord

Corticotropin-releasing factor (CRF) and urocortin 1 (Ucn1) are involved in stress adaptation. CRF receptor 1 (CRF1) binds CRF and Ucn1 with similar high affinity, but CRF receptor 2 (CRF2) binds Ucn1 with higher affinity than CRF. We tested the hypothesis that in the spinal cord CRF and Ucn1 control peripheral components of the stress response, by assessing the distribution of CRF- and Ucn1-containing fibers, CRF1 and CRF2 mRNAs, and CRF receptor protein (CRFR) in the mouse spinal cord, by using immunofluorescence and in situ hybridization. CRF, Ucn1, and CRFR occurred throughout the spinal cord. CRF fibers predominated in laminae I, V-VII, and X of Rexed. Ucn1 fibers occurred mainly in laminae VII and X and occasionally in lamina IX. Both CRFR mRNAs occurred in all laminae except the superficial laminae of the dorsal horn, but they exhibited different distributions, CRF2 mRNA having a wider occurrence (laminae III-X) than CRF1 mRNA (laminae III-VIII). Double immunofluorescence indicated that CRF and Ucn1 fibers contacted CRFR-containing neurons, mainly in laminae VII and X. The strongest co-distribution of CRF1 and CRF2 mRNAs with CRF and Ucn1 fibers appeared in lamina VII. CRF2 mRNA predominated in lamina IX together with Ucn1, whereas CRF2 mRNA predominated in lamina X, where it had similar distributions with each ligand. In view of the lamina-specific and similar distributions of the two CRF receptor mRNAs with their ligands, we suggest that CRF1 and CRF2 are involved in peripheral stress adaptation processes, such as modulation of stress-induced analgesia and the mediation of visceral nociceptive information by CRF2.