Sex differences in the anatomical and functional organization of the periaqueductal gray-rostral ventromedial medullary pathway in the rat: A potential circuit mediating the sexually dimorphic actions of morphine
Version of Record online: 13 APR 2006
Copyright © 2006 Wiley-Liss, Inc.
Journal of Comparative Neurology
Volume 496, Issue 5, pages 723–738, 10 June 2006
How to Cite
Loyd, D. R. and Murphy, A. Z. (2006), Sex differences in the anatomical and functional organization of the periaqueductal gray-rostral ventromedial medullary pathway in the rat: A potential circuit mediating the sexually dimorphic actions of morphine. J. Comp. Neurol., 496: 723–738. doi: 10.1002/cne.20962
- Issue online: 13 APR 2006
- Version of Record online: 13 APR 2006
- Manuscript Accepted: 10 JAN 2006
- Manuscript Revised: 8 SEP 2005
- Manuscript Received: 24 JUN 2005
- National Institutes of Health. Grant Numbers: DA16272, AR49555
- endogenous descending pathway;
- morphine analgesia
Previous studies have demonstrated that morphine, administered systemically or directly into the periaqueductal gray (PAG), produces a significantly greater degree of antinociception in males in comparison with females. Because the midbrain PAG and its descending projections to the rostral ventromedial medulla (RVM) constitute an essential neural circuit for opioid-based analgesia, the present studies were conducted to determine whether sex differences in the anatomical organization of the PAG-RVM pathway, and its activation during persistent inflammatory pain, could account for sex-based differences in opioid analgesia. In the rat, retrograde tracing was combined with Fos immunocytochemistry to investigate sexual dimorphism in the organization of the PAG-RVM circuit and its activation by persistent inflammatory pain induced by intraplantar injection of complete Freund's adjuvant (CFA). The ability of morphine to suppress the activation of the PAG-RVM circuit was also examined. Sexually dimorphic retrograde labeling was observed within the dorsomedial and lateral/ventrolateral PAG at all rostrocaudal levels, with females having significantly more PAG-RVM output neurons in comparison with males. While no sex differences were noted in the activation of the PAG by persistent inflammatory pain, significantly more PAG-RVM cells were activated in males in comparison with females. Systemic administration of morphine significantly suppressed CFA-induced Fos in the PAG in males only. The results of these studies demonstrate that both the anatomical organization and the functional activation of the PAG-RVM circuit are sexually dimorphic and may provide the anatomical substrate for sex-based differences in morphine analgesia. J. Comp. Neurol. 496:723–738, 2006. © 2006 Wiley-Liss, Inc.