40. Regarding Central Nervous System Mechanisms of Pain Modulation, which of the following statement is least likely: (A) Pain-modulating systems involve a network with major relays in the midbrain periaqueductal gray and rostral ventrolateral medulla. (B) This network exerts bidirectional control over dorsal horn nociceptive transmission by means of separate anti- and pro-nociceptive output from the RVM. (C) The PAG–RVM system is the central substrate for the actions of opioid and non-opioid analgesic drugs. (D) The PAG–RVM system receives direct and indirect input from nociceptive transmission pathways to modulate nociception. (E) It strongly links with the hypothalamus and limbic forebrain , through which cognitive and emotional factors can regulate pain processing.