Research Papers Parabrachial area and nucleus raphe magnus inhibition of corneal units in rostral and caudal portions of trigeminal subnucleus caudalis in the rat Ian D. Meng a,1 , James W. Hu b , David A. Bereiter a,c, * a Department of Neuroscience, Brown University/Rhode Island Hospital, Providence, RI 02903, USA b Faculty of Dentistry, University of Toronto, Toronto, Ontario M5G 1G6, Canada c Department of Surgery, Neuroendocrine Laboratory, Brown University/Rhode Island Hospital, Providence, RI 02903-4970, USA Received 6 July 1999; received in revised form 8 February 2000; accepted 9 March 2000 Abstract The cornea has been used extensively as a means to selectively stimulate trigeminal nociceptive neurons. The aim of this study was to determine the effects of descending modulatory control pathways on corneal unit activity by comparing the effects of conditioning stimulation of the pontine parabrachial area (PBA CS) and nucleus raphe magnus (NRM CS). Electrical stimulation of the cornea at A- and C-®ber intensities was used to activate neurons in two regions of the trigeminal spinal nucleus, the subnucleus interpolaris/caudalis transition (Vi/Vc, `rostral units') and laminae I±II at the subnucleus caudalis/cervical cord transition (Vc/C1, `caudal units'), in chloralose- anesthetized rats. Corneal units were further classi®ed according to convergent cutaneous receptive ®eld properties and PBA projection status. None of 48 rostral and 23/28 caudal units projected to the ipsilateral or contralateral PBA. PBA CS inhibited the cornea-evoked responses (,75% change from control) of approximately 65% of rostral and caudal units regardless of neuronal class. For rostral corneal units, PBA CS inhibited A- and C-®ber input equally (15 ^ 3 and 18 ^ 14% of control, respectively), whereas among caudal units, A-®ber input was inhibited more than C-®ber input (26 ^ 5 and 64 ^ 12% of control, respectively, P , 0:01). The magnitude of NRM CS inhibition on cornea-evoked activity of both rostral and caudal units was not different from that seen after PBA CS. Glutamate microinjections into PBA also inhibited rostral and caudal corneal units (6/9 tested). These results indicate that corneal input to rostral and caudal units is modi®ed by activation of descending controls from the PBA and NRM. The signi®cance for processing corneal sensory information is discussed in terms of functional differences between rostral and caudal neurons. q 2000 International Association for the Study of Pain. Published by Elsevier Science B.V. All rights reserved. Keywords: Cornea; Descending modulation; Parabrachial; A7; Ko Èlliker±Fuse nucleus; Nucleus raphe magnus 1. Introduction The corneal afferent system has been used as a model for the study of trigeminal nociception. The corneal surface is accessible, innervated exclusively by small diameter primary afferents, and psychophysical studies have demon- strated that corneal stimulation evokes mainly sensations of irritation or pain (Zander and Weddell, 1951; Kenshalo, 1960; Whitear, 1960; Beuerman and Tanelian, 1979). Tract tracing of central projections of corneal primary affer- ent ®bers (Marfurt and Del Toro, 1987) and c-fos immuno- cytochemistry after noxious corneal stimulation (Lu et al., 1993; Strassman and Vos, 1993; Meng and Bereiter, 1996) have identi®ed two regions of the trigeminal spinal nucleus (Vsp) as receiving corneal input: the ventral portion of Vsp at the transition between trigeminal subnucleus interpolaris and subnucleus caudalis (Vi/Vc, rostral transition region), and the most caudal portion of subnucleus caudalis at the spinomedullary junction (Vc/C1, caudal transition region). It has been suggested that the rostral transition region represents an extension of laminae I±II of Vc based on similar cell morphology and neuropeptide content (South and Ritter, 1986; Kruger et al., 1988; Phelan and Falls, 1989; Schults, 1992). Despite these anatomical similarities, recent recording studies found signi®cant differences in response properties of second-order cornea-responsive neurons at the rostral and caudal transition regions (Meng et al., 1997). Neurons in laminae I±II at the caudal transition region that responded to corneal input each had a conver- gent cutaneous receptive ®eld (RF) that responded to noxious mechanical, thermal and chemical stimulation, and 80% of neurons tested projected to the contralateral Pain 87 (2000) 241±251 0304-3959/00/$20.00 q 2000 International Association for the Study of Pain. Published by Elsevier Science B.V. All rights reserved. PII: S0304-3959(00)00289-X www.elsevier.nl/locate/pain * Corresponding author. Tel.: 11-401-444-4277; fax: 11-401-444-8052. E-mail address: dbereiter@lifespan.org (D.A. Bereiter). 1 Present address: Department of Neurology, University of California, San Francisco, CA 94143-0453, USA.