Which brain region is primarily involved in the descending pain modulatory pathway, and how do opioids influence this area to reduce pain?

The rostral ventromedial medulla (RVM) is a key brain region primarily involved in the descending pain modulatory pathway. The descending pain modulatory pathway is a network of brain structures that can either enhance or inhibit pain signals ascending from the spinal cord to the brain. The RVM, located in the brainstem, receives input from several other brain regions, including the periaqueductal gray (PAG) and the prefrontal cortex, and sends projections down to the dorsal horn of the spinal cord. Opioids influence the RVM to reduce pain by activating mu (μ) opioid receptors in this region. Activation of these receptors modulates the activity of RVM neurons, which include both 'on-cells' that facilitate pain and 'off-cells' that inhibit pain. Opioids inhibit the 'on-cells' and activate the 'off-cells,' thereby suppressing the transmission of pain signals from the spinal cord. The RVM then releases neurotransmitters, such as serotonin and norepinephrine, into the dorsal horn of the spinal cord, where they inhibit the activity of pain-transmitting neurons. This descending inhibition reduces the perception of pain. Therefore, the RVM acts as a critical relay station in the descending pain modulatory pathway, and opioids exert their analgesic effects, in part, by modulating the activity of this brain region to suppress pain signals.