Neurons in the rostral ventromedial medulla (RVM) are the major source of serotonergic projections to the dorsal horn. A large body of evidence implicates RVM serotonergic neurons in the modulation of spinal nociceptive transmission. Three physiological classes of RVM neurons, on, off, and neutral cells, are postulated to have different nociceptive modulatory effects on spinal nocifensor reflexes. This study was undertaken to determine which RVM cell class(es) contains 5- HT. In anesthetized rats, RVM neurons were identified by their responses to noxious cutaneous stimuli, intracellularly labeled, and processed for 5-HT immunocytochemistry. Labeled neurons were examined with epifluorescence and imaged using a confocal laser microscope. A total of 25 RVM neurons were intracellularly labeled. No off (n = 9) or on (n = 8) cells were serotonergic. Half of the neutral cells (4 of 8) demonstrated 5-HT immunoreactivity. These results call for a reevaluation of the mechanisms of RVM modulatory influence on spinal cord nociceptive transmission. The finding that some neutral cells are serotonergic strongly suggests that serotonergic neutral cells are involved in the modulation of spinal nociceptive transmission. Additionally, inhibition of spinal nociceptive transmission by off cells is unlikely to involve 5-HT release. Finally, since opioid administration does not alter the firing of RVM neutral cells, the results of the present study indicate that serotonergic RVM neurons do not directly mediate the effects of supraspinal opioids in the rat.

Methods: A Choosing Wisely Working Group of 10 AAN members was formed to oversee the process and craft the evidence-based recommendations. AAN members were solicited for recommendations, the recommendations were sent out for external review, and the Working Group members (article authors) used a modified Delphi process to select their Top Five Recommendations. Results and recommendations:The Working Group submitted 5 neurologic recommendations to the AAN Practice Committee and Board of Directors; all 5 were approved by both entities in September 2012. Recommendation 1: Don't perform EEGs for headaches. Recommendation 2: Don't perform imaging of the carotid arteries for simple syncope without other neurologic symptoms. Recommendation 3: Don't use opioids or butalbital for treatment of migraine, except as a last resort. Recommendation 4: Don't prescribe interferon-b or glatiramer acetate to patients with disability from progressive, nonrelapsing forms of multiple sclerosis. Recommendation 5: Don't recommend carotid endarterectomy for asymptomatic carotid stenosis unless the complication rate is low (,3%). Alzheimer disease, Parkinson disease, stroke, and multiple sclerosis affect approximately 15 million people and account for more than $290 billion in health care spending annually in the United States.