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Abstract

The rostral ventromedial medulla (RVM) regulates pain through ON- and OFF-cell populations, which facilitate or inhibit nociception. This thesis contrasts their roles in acute versus chronic pain and explores interactions with core functions such as respiration. In acute injury, ON-cell activity drives hyperalgesia, but in chronic inflammation, ON-cell inhibition exacerbates pain, indicating distinct mechanisms. Respiratory monitoring revealed that ON-cells modulate both pain and respiration, while OFF-cells primarily mediate analgesia. Opioid effects in the RVM confirmed separable pathways for analgesia and respiratory depression. These findings advance understanding of RVM physiology and suggest strategies for developing non-respiratory-depressant analgesics.

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