INTRODUCTION It is known that spinal nociception is subject to descending inhibitory modulation from supraspinal structures (see Basbaum & Fields, 1978, 1984; Hammond, 1986; Gebhart & Randich, 1990; Fields et al., 1991; Willis, 1988; Sandkühler, 1996; Willis & Westlund, 1997 for reviews). Descending inhibition of spinal nociception from the periaqueductal gray (PAG) and rostral ventral medulla (RVM) has been characterized. Activation of neurons within the PAG or RVM decreases responses to noxious stimuli of spinal dorsal horn neurons, including ascending projection neurons [e.g. spinothalamic tract cells (STTs)], and inhibits behavioral nociceptive reflexes. Descending inhibitory influences are believed to be impor- tant for the analgesic effects of opioids and cannabinoids as well as stimulation-produced analgesia (Basbaum & Fields, 1984; Fields et al., 1988; 1991; Meng et al., 1998; Mitchell et al., 1998). It has been suggested that the anterior cingu- late cortex (ACC) forms part of the affective Descending facilitatory modulation of a behavioral nociceptive response by stimulation in the adult rat anterior cingulate cortex Amelita A. Calejesan a , Susan J. Kim a and Min Zhuo* ,b a Department of Anesthesiology, b Department of Anatomy and Neurobiology, Washington University Medical Center, Washington University in St. Louis, St. Louis, MO 63110, USA It is well documented that the descending endogenous analgesia system, including the periaqueductal gray (PAG) and the rostral ventral medulla (RVM), play an important role in modulation of nociceptive transmis- sion and morphine- and cannabinoid-produced analgesia.Neurons in the PAG receive inputs from different nuclei of higher structures, including the anterior cingulate cortex (ACC). However, it is unclear if stimulation of neurons in the ACC modulates spinal nociceptive transmission. The present study has examined the effects of electrical stimulation and chemical activation of metabotropic glutamate receptors (mGluRs) in the ACC on a spinal nociceptive tail-flick (TF) reflex induced by noxious heating. Activation of the ACC at high inten- sities (up to 500 μA) of electrical stimulation did not produce any antinociceptive effect. Instead, at most sites within the ACC (n = 36 of 41 sites), electrical stimulation produced significant facilitation of the TF reflex (i.e. decreases in TF latency). Chemical activation of mGluRs within the ACC also produced a facilitatory effect. Descending facilitation from the ACC apparently relays at the RVM. Electrical stimulation in the RVM produces a biphasic modulatory effect, showing facilitation at low intensities and inhibition at higher intensi- ties. The present study provides evidence that activation of mGluRs within the ACC can facilitate spinal noci- ception. © 2000 European Federation of Chapters of the International Association for the Study of Pain KEYWORDS: descending facilitation, anterior cingulate cortex, tail-flick reflex, rostral ventral medulla, metabotropic glutamate receptor, rat. Paper received 1 July 1999 and accepted in revised form 27 December 1999. Correspondence to: Min Zhuo, Department of Anesthesiology, Washington University Medical Center, Washington University in St. Louis, St. Louis, MO63110, USA Tel: 314 747 0416; Fax: 314 862 1571; Email: Zhuom@morpheus.wustl.edu 1090-3801/00/010083 + 14 $35.00/0 © 2000 European Federation of Chapters of the International Association for the Study of Pain European Journal of Pain (2000) 4: 83–96 doi:10.1053/eujp.1999.0158, available online at http://www.idealibrary.com on