Substance P, calcitonin gene related peptide and PGE2 co-released from the mouse colon: a new model to study nociceptive and inflammatory responses in viscera, in vitro.
Visceral inflammation is thought to play an important role in the sensitization of low and high threshold mechanosensory and polymodal afferents and to recruit silent nociceptors. Yet, little is known about the potential role of the mediators involved in nociceptor sensitization to mechanical stimulation as compared to heat sensitization in the skin. In the present study we developed a new isolated preparation of the mouse colon which allowed to apply controlled mechanical distensions. Excised segments of colon from CD mice were immersed in synthetic interstitial fluid (SIF) exposing the serosal surface during 5 min to different types of noxious stimuli; the increase in neuropeptide and PGE(2) release were analyzed (by EIA technique). Capsaicin, heat and pH 5.2 were able to induce significant increases in calcitonin gene related peptide (CGRP) release (14.6-, 5.1-, and 2.3-fold over baseline), however, only capsaicin induced a significant increase in substance P (SP) levels (1.8-fold over baseline). When pH 3.4 was used, a massive liberation of both CGRP and SP was obtained (14- and 15-fold from baseline) which was Ca(2+)-independent and not recovering, suggesting unphysiological release. Mechanical distensions in the noxious range (45, 60 and 90 mmHg) evoked a long-linear graded release of CGRP (1.3-, 1.6- and 2.6-fold over baseline) and of PGE(2) (1.9- 3.8-, 12.3-fold over baseline). Only the 90 mmHg distension evoked a significant increase of SP (1.9-fold over baseline). We conclude that the mouse colon preparation is a suitable model to study inflammatory and nociceptive mechanisms in viscera. Furthermore, a potentially important and yet unexplored role of PGE(2) in noxious visceral distension has been revealed.
Roza
C
C
Department of Physiology and Experimental Pathophysiology, University of Erlangen-Nuremberg, Universitätsstrasse 17, D-91054 Erlangen, Germany.
Reeh
P W
PW
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism*; D003106:Colon / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism*; D005260:Female; D006358:Hot Temperature / Q000009:adverse effects; D007249:Inflammation / Q000378:metabolism*; D008297:Male; D051379:Mice; D010147:Pain Measurement / Q000379:methods*; D013373:Substance P / Q000378:metabolism*; D014781:Viscera / Q000378:metabolism
D013373:Substance P; D015740:Calcitonin Gene-Related Peptide; D015232:Dinoprostone