Early increase and later decrease in VIP and substance P nerve fiber densities following abdominal radiotherapy: a study on the human colon.
OBJECTIVE
The neuropeptides substance P (SP) and vasoactive intestinal peptide (VIP) mediate physiologic activities in the intestine, not least in relation to motility and inflammatory processes. Neuropeptides are up-regulated and play particular importance during tissue stress. This paper aims to quantify mucosal and smooth muscle SP, VIP and total innervation in human colon in short- and long-term perspectives after abdominal irradiation.


METHODS
Colon specimens from 23 irradiated or non-irradiated patients were investigated with immunohistochemistry and computerized image analysis. Plasma levels of SP and VIP in 15 additional patients receiving radiotherapy were analyzed.


RESULTS
At 4-7 days after irradiation (5 x 5 Gy), the overall innervation, and also VIP and SP nerve fiber densities, were increased in both mucosa and circular muscle layer. In contrast, 5-6 weeks as well as several years after irradiation, the VIP and SP nerve fiber densities were decreased. No peptide changes were revealed in plasma.


CONCLUSIONS
The degree of VIP and SP intestinal innervation was increased after radiotherapy in the short-term perspective but it decreased in the long-term. In the short-term, SP may have pro-inflammatory and VIP anti-inflammatory effects and the peptides may have trophic effects and be related to the occurrence of motor changes. It cannot be excluded that the decrease in VIP and SP neuronal supply seen in the long-term may contribute to intestinal malfunction.
Höckerfelt
U
U
Department of Integrative Medical Biology, Section for Anatomy, Umeå University, SE-901 87 Umeå, Sweden.
Franzén
L
L
Norrgård
O
O
Forsgren
S
S
D000005:Abdomen; D000368:Aged; D002277:Carcinoma / Q000532:radiotherapy; D002452:Cell Count; D003106:Colon / Q000294:innervation* / Q000473:pathology / Q000528:radiation effects; D003110:Colonic Neoplasms / Q000532:radiotherapy*; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000294:innervation / Q000473:pathology / Q000528:radiation effects; D008297:Male; D008875:Middle Aged; D009130:Muscle, Smooth / Q000294:innervation / Q000473:pathology / Q000528:radiation effects; D009412:Nerve Fibers / Q000378:metabolism* / Q000473:pathology / Q000528:radiation effects*; D009474:Neurons / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects; D010388:Pelvis; D011829:Radiation Dosage; D011863:Radioimmunoassay; D012004:Rectal Neoplasms / Q000532:radiotherapy*; D013373:Substance P / Q000097:blood / Q000378:metabolism*; D013869:Thiolester Hydrolases / Q000096:biosynthesis; D013995:Time; D043222:Ubiquitin Thiolesterase; D014660:Vasoactive Intestinal Peptide / Q000097:blood / Q000378:metabolism*
D013373:Substance P; D014660:Vasoactive Intestinal Peptide; D013869:Thiolester Hydrolases; D043222:Ubiquitin Thiolesterase