| Anatomical and physiological studies conducted in the early 1960s identified the midbrain periaqueductal gray (PAG), and its descending projections to the brainstem rostral ventromedial medulla (RVM) and spinal cord dorsal horn, as a primary anatomical pathway mediating opioid-based analgesia. Since these initial studies, the PAG-RVM-spinal cord pathway has been characterized in the majority of vertebrate species. Remarkably, these studies were conducted exclusively in males; therefore, little is known about the anatomy and physiology of this circuit in females. It is now well established that morphine produces a significantly greater degree of analgesia in males compared to females, and recent studies in a rat model of persistent pain indicate that the PAG-RVM pathway contributes to the sexually dimorphic actions of morphine. Given that the PAG and its descending projections to the RVM and dorsal horn spinal cord, provide a primary pathway for the actions of exogenous opioids on pain modulation, this dissertation addressed the following questions: (1) are there sex differences in the anatomical organization of the PAG-RVM pathway; (2) is there a sexually dimorphic response of the PAG-RVM pathway to persistent pain; and (3) does administration of morphine differentially engage the PAG-RVM pathway in male and female rats?;Index words: periaqueductal gray, rostral ventromedial medulla, endogenous descending pathway, antinociception, nociception, inflammation... |
