Traction on the mesentery as a model of visceral nociception.
Traction of the mesentery is known to induce strong autonomic reactions in patients undergoing abdominal surgery. An experimental model using this stimulus in anaesthetized rats has been developed, which allows the comparison of noxious mechanical and chemical stimulation of the mesentery. Graded traction on a bundle of jejunal vessels with 2-30 g led to reflex changes in blood pressure and intragastric pressure, the size of which correlated with the strength of the stimulus. Comparable responses were elicited by clamping the same vessels either at their distal or proximal end or by applying 100 microl 0.6% acetic acid or 0. microM bradykinin. These reflexes are fairly insensitive towards impairment of the autonomic system. Only the combination of phentolamine and propranolol reduced the cardiovascular responses to all stimuli but at the same time, significantly lowered basal blood pressure. The adrenoceptor antagonists affected the gastric response to acid only. Atropine on its own was ineffective. Administered together with the combination of adrenoceptor blockers it had no further influence on the cardiovascular reflexes but significantly reduced the gastric responses to stretch, proximal clamping and acid. Acute desensitization of small diameter afferents with capsaicin almost abolished the reflex responses to acid. The cardiovascular, but not the gastric, response to traction was reduced by capsaicin. Morphine led to dose-dependent reductions of the reflex responses in a naloxone-reversible manner, whereas indomethacin was inactive. The bradykinin B2-antagonist icatibant abolished the reflex in response to the application of bradykinin but not to acid or traction. It is concluded that the measurement of the cardiovascular and gastric responses of anaesthetized rats to traction on the mesentery is a suitable method to investigate acute visceral nociception. Chemical stimuli to the mesentery are transmitted by capsaicin-sensitive afferents, but there is a dichotomy regarding capsaicin's influence on visceral mechanonociception. Opioid mechanisms are always involved, whereas prostaglandins or bradykinin have no role in the reflexes evoked by acid or traction. Intact alpha- or beta-adrenergic (as tested with unselective receptor antagonists) or muscarinic mechanisms are required for the reaction of the end organs in the reflex but they have no role in the afferent or central processing.
Holzer-Petsche
U
U
Department of Experimental and Clinical Pharmacology, Karl-Franzens-University, Graz, Austria. ulrike.holzer@kfunigraz.ac.at
Brodacz
B
B
D000758:Anesthesia; D000818:Animals; D001341:Autonomic Nervous System / Q000503:physiopathology; D001794:Blood Pressure; D004195:Disease Models, Animal; D005260:Female; D008643:Mesentery / Q000503:physiopathology*; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology; D009619:Nociceptors / Q000502:physiology*; D010146:Pain / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013270:Stomach / Q000503:physiopathology; D013314:Stress, Mechanical; D014781:Viscera / Q000503:physiopathology*