Abstract
A potential role for neurotensin in the rostral ventromedial medulla (RVM) in modulation of visceral nociceptive transmission was examined in this study. Microinjection of neurotensin (3–3000 pmol) into the RVM of awake rats produced a dose-dependent inhibition of the visceromotor response (VMR) to noxious colorectal distension (CRD) that lasted 30 to 120 min. Additionally, intra-RVM injection of neurotensin (300 pmol) significantly reduced the slope of the stimulus-response function to graded CRD (20–80 mm Hg), whereas the greatest dose of neurotensin (3000 pmol) completely inhibited the VMR at all intensities of CRD. General motor function was unaffected after intra-RVM injection of neurotensin (3000 pmol). Intra-RVM injection of lesser doses of neurotensin (0.03–0.30 pmol) resulted an enhancement of the VMR to noxious CRD that had a short duration (18–30 min), and produced a leftward shift of the stimulus-response function to graded CRD without a change in the slope of the function. Additionally, intra-RVM injection of the neurotensin-receptor antagonist SR48692 (0.3–300 fmol) in naive animals produced dose-dependent inhibition of VMR to noxious CRD, whereas a lesser dose (0.03 fmol) enhanced the VMR. These data support a role for neurotensin in the RVM in biphasic modulation of visceral nociception. The results obtained with SR48692 suggest that endogenous neurotensin in the RVM modulates VMR to noxious CRD via a prominent interaction with neurotensin receptors that mediate facilitatory influences and a lesser interaction with neurotensin receptors that mediate masked inhibitory influences.
Footnotes
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Send reprint requests to: Mark O. Urban, Ph.D., Department of Pharmacology, Bowen Science Building, University of Iowa, Iowa City, IA 52242. E-mail: murban{at}blue.weeg.uiowa.edu
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↵1 The study was supported by National Institutes of Health Grants DA-11431 (M.O.U.) and DA-02879 (G.F.G.).
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↵2 Present address: UCLA/CURE Neuroenteric Disease Program, WLA VA Medical Center, Building 115, Room 223, 11301 Wilshire Boulevard, Los Angeles, CA 90073.
- Abbreviations:
- CNS
- central nervous system
- CRD
- colorectal distension
- RMg
- nucleus raphe magnus
- RVM
- rostral ventromedial medulla
- VMR
- visceromotor response
- Received December 28, 1998.
- Accepted March 2, 1999.
- The American Society for Pharmacology and Experimental Therapeutics
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