Volume 122, Issue 4, Pages 1007-1019 (April 2002) Facilitation and attenuation of a visceral nociceptive reflex from the rostroventral medulla in the rat  Min Zhuo, G.F. Gebhart  Gastroenterology  Volume 122, Issue 4, Pages 1007-1019 (April 2002) DOI: 10.1053/gast.2002.32389 Copyright © 2002 American Gastroenterological Association Terms and Conditions

Fig. 1 Example of peritoneal musculature contraction to noxious colorectal distention (80 mm Hg; 20 seconds) quantified as the electromyogram (EMG). The EMG and corresponding peristimulus time histogram (1-second bin width) are illustrated. The horizontal dotted line represents the discriminator threshold. Gastroenterology 2002 122, 1007-1019DOI: (10.1053/gast.2002.32389) Copyright © 2002 American Gastroenterological Association Terms and Conditions

Fig. 2 Summary of sites in the rostroventral medulla where electrical stimulation produced only inhibition (○), only facilitation (▴), or biphasic modulation (●) of the visceromotor response to noxious colorectal distention (80 mm Hg, 20 seconds). Sites where electrical stimulation did not produce effects are also shown (□). Stimulation sites were reconstructed from histologic sections of the rat brainstem and are summarized on coronal brain sections26 referenced to distance in millimeters posterior to Bregma (Bregma −10.30 being most rostral). NPGCl, nucleus reticularis paragigantocellularis lateralis; Pyr, pyramidal tract; Sp5, spinal trigeminal tract; and VII, facial nucleus. Gastroenterology 2002 122, 1007-1019DOI: (10.1053/gast.2002.32389) Copyright © 2002 American Gastroenterological Association Terms and Conditions

Fig. 3 Examples of (A) biphasic and (B) inhibitory modulation of the visceromotor response produced by electrical stimulation in the RVM. (A and B) Peristimulus time histograms (1-second bin width) of the visceromotor responses to noxious colorectal distention (80 mm Hg) before and during stimulation (intensities given). The period of distention (20 seconds) is indicated by the horizontal bar, and the period of RVM stimulation (25 seconds) is indicated by the arrows. (C) Graphic representation of the data in A and B; the point above 0 represents the response to distention (total counts in 20 seconds) in the absence of stimulation. (D) Brainstem stimulation sites, illustrated on a representative coronal brain section.26 Abbreviations are the same as in Figure 2. Gastroenterology 2002 122, 1007-1019DOI: (10.1053/gast.2002.32389) Copyright © 2002 American Gastroenterological Association Terms and Conditions

Fig. 4 Summary of descending modulation of the visceromotor response from the RVM. (A–C) Visceromotor responses to noxious colorectal distention (80 mm Hg) are presented as a percentage of the control response (total counts in 20 seconds) against the intensity of stimulation in the RVM for (A) inhibitory, (B) facilitatory, and (C) biphasic modulation. (D) Summary of data in A, B, and C. Gastroenterology 2002 122, 1007-1019DOI: (10.1053/gast.2002.32389) Copyright © 2002 American Gastroenterological Association Terms and Conditions

Fig. 5 Effects of stimulation in the RVM on SRFs to graded colorectal distention. (A and C) Control SRFs of individual animals in the absence of stimulation in the brainstem. Data are plotted as the response to distention (total counts in 20 seconds) against distention pressure. (B and D) Summary of effects of (B) facilitatory and (D) inhibitory stimulation in the RVM on the mean SRFs of data illustrated in A and C, respectively. Data are presented as mean response in the absence (○, control) and presence (●) of stimulation. (E) Sites of facilitatory (● and ◑) and inhibitory (○ and ◑) stimulation. Gastroenterology 2002 122, 1007-1019DOI: (10.1053/gast.2002.32389) Copyright © 2002 American Gastroenterological Association Terms and Conditions

Fig. 6 Example of the inhibitory effect of glutamate microinjection (50 nmol) into the RVM on the visceromotor response to noxious colorectal distention (80 mm Hg). (A) Peristimulus time histograms (1-second bin width) illustrating responses to distention before (top) and 1, 4, 7, and 10 minutes after glutamate microinjection. (B) Graphic representation of data in A. The point above C represents the baseline response to distention (total counts in 20 seconds) and the points above stim indicate inhibitory effects produced by electrical stimulation (intensities given) at the same site in the brainstem. Glutamate (50 nmol) was subsequently given into the same site as stimulation and inhibited the response to distention. (C) Site of brainstem stimulation/glutamate microinjection. Abbreviations are the same as in Figure 2. Gastroenterology 2002 122, 1007-1019DOI: (10.1053/gast.2002.32389) Copyright © 2002 American Gastroenterological Association Terms and Conditions

Fig. 7 Summary of glutamate-produced effects. (A) Mean peristimulus time histograms (PSTHs; 1-second bin width) representing the mean visceromotor response before glutamate administration (unfilled PSTHs) and at 1 minute after glutamate administration (filled PSTHs). The period of distention (20 seconds) is indicated below by the horizontal bar. (B) Graphic representation of the data in A and time course of effect. The data are presented as a percentage of the control response (total counts in 20 seconds). (C) Brainstem sites for glutamate microinjection at a low dose (5 nmol; ●) and a greater dose (50 nmol; ○). At 3 sites (indicated by ◑), both doses of glutamate (5 and 50 nmol) were tested. Gastroenterology 2002 122, 1007-1019DOI: (10.1053/gast.2002.32389) Copyright © 2002 American Gastroenterological Association Terms and Conditions

Fig. 8 Summary of reproducibility of glutamate-produced facilitation and inhibition. (A) Mean peristimulus time histograms (PSTHs; 1-second bin width) representing the mean visceromotor responses before glutamate administration (unfilled PSTHs) and at 1 minute after glutamate administration (filled PSTHs). The period of distention (20 seconds) is indicated below by the horizontal bar. On the left, mean responses before and after the first glutamate administration at doses of 5 or 50 nmol are illustrated on top and bottom, respectively. Responses before and after the second glutamate administration at the same site are illustrated on the right top and bottom, respectively. (B) Graphic illustrations of the data in A expressed as a percentage of control responses to distention. (C) Summary of sites where glutamate at a low dose (5 nmol; ○) or greater dose (50 nmol; ●) was administered. At 2 sites (◑), both low and high doses of glutamate were tested. Abbreviations are the same as in Figure 2. Gastroenterology 2002 122, 1007-1019DOI: (10.1053/gast.2002.32389) Copyright © 2002 American Gastroenterological Association Terms and Conditions

Fig. 9 Summary of effects of unilateral (ipsilateral or contralateral) lidocaine microinjection into the ventral part of the spinal cord. (A and B) Effects on stimulation-produced facilitation and inhibition of the visceromotor response, respectively. The mean response to noxious colorectal distention (80 mm Hg) is presented as a percentage of control (total counts in 20 seconds). Stimulation-produced effects before lidocaine microinjection are indicated by unfilled bars. (C) Histologic reconstruction of sites in the spinal cord for lidocaine microinjection. (D) Brainstem stimulation sites for inhibitory (○) or facilitatory (●) modulation. At 5 sites (indicated by ◑), both facilitatory and inhibitory modulation produced by stimulation at lesser and greater intensities, respectively, was tested. Abbreviations are the same as in Figure 2. *Significantly less than corresponding control (P < 0.05). Gastroenterology 2002 122, 1007-1019DOI: (10.1053/gast.2002.32389) Copyright © 2002 American Gastroenterological Association Terms and Conditions

Fig. 10 Summary of effects of bilateral transection of the DLFs. (A) Effects on stimulation-produced facilitatory and inhibitory effects. Responses to noxious colorectal distention (80 mm Hg) are presented as percentage of control (total counts in 20 seconds). □, Stimulation-produced effects before bilateral DLF transections. (B) Brainstem stimulation sites for inhibitory (○) or facilitatory (●) modulation. At 1 site (◑), both facilitatory and inhibitory modulation produced by stimulation at lesser and greater intensities, respectively, were tested. (C) Histologic reconstruction of DLF transections. Abbreviations are the same as in Figure 2. *Significantly different from corresponding control (P < 0.05). Gastroenterology 2002 122, 1007-1019DOI: (10.1053/gast.2002.32389) Copyright © 2002 American Gastroenterological Association Terms and Conditions