A new possibility for repairing the anal dysfunction by promoting regeneration of the reflex pathways in the enteric nervous system.
Moderate rectal distension elicits recto-rectal reflex contractions and simultaneous recto-internal anal sphincter reflex relaxations that together comprise the defecation reflex. Both reflexes are controlled by 1) pelvic nerves, 2) lumbar colonic nerves, and 3) enteric nervous system. The aim of the present study was to explore a novel approach to repairing the defecation reflex dysfunction by using the plasticity of enteric nervous pathways. Experiments were performed in anesthetized guinea pigs with ethyl carbamate. The rectum 30 mm oral from the anal verge was transected without damage to extrinsic nerves, and subsequent end-to-end one-layer anastomosis was performed. Recovery of the defecation reflex and associated reflex pathways were evaluated. Eight weeks after sectioning of intrinsic reflex nerve pathways in the rectum, the defecation reflex recovered to the control level, accompanied with regeneration of reflex pathways. The 5-HT(4)-receptor agonist mosapride (0.5 and 1.0 mg/kg) significantly (P < 0.01) enhanced the recovered defecation reflex 8 wk after surgery. Two weeks after local treatment with brain-derived neurotrophic factor (BDNF: 10(-6) g/ml) at the rectal anastomotic site, the recto-internal anal sphincter reflex relaxations recovered and some bundles of fine nerve fibers were shown to interconnect the oral and anal ends of the myenteric plexus. These results suggested a possibility for repairing the anal dysfunction by promoting regeneration of the reflex pathways in the enteric nervous system with local application of BDNF.
Katsui
Renta
R
Dept. of Physiology II, Nara Medical Univ., 840 Shijo-cho, Kashihara 634-8521, Japan.
Kojima
Yu
Y
Kuniyasu
Hiroki
H
Shimizu
Juichiro
J
Koyama
Fumikazu
F
Fujii
Hisao
H
Nakajima
Yoshiyuki
Y
Takaki
Miyako
M
D001003:Anal Canal / Q000294:innervation* / Q000503:physiopathology / Q000601:surgery; D000714:Anastomosis, Surgical; D000818:Animals; D001549:Benzamides / Q000494:pharmacology*; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology; D049109:Cell Proliferation; D003672:Defecation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D017615:Enteric Nervous System / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology* / Q000601:surgery; D005765:Gastrointestinal Agents / Q000494:pharmacology; D006168:Guinea Pigs; D018398:Homeodomain Proteins / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D009025:Morpholines / Q000494:pharmacology*; D009416:Nerve Regeneration / Q000187:drug effects; D009419:Nerve Tissue Proteins; D016900:Neurofilament Proteins / Q000378:metabolism; D009473:Neuronal Plasticity / Q000187:drug effects; D011312:Pressure; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D020813:Receptor, trkB / Q000378:metabolism; D017978:Receptors, Growth Factor; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism; D020127:Recovery of Function; D012007:Rectum / Q000294:innervation* / Q000503:physiopathology / Q000601:surgery; D012018:Reflex / Q000187:drug effects; D058828:Serotonin 5-HT4 Receptor Agonists; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism
D001549:Benzamides; D019208:Brain-Derived Neurotrophic Factor; C088334:Distal-less homeobox proteins; D005765:Gastrointestinal Agents; D018398:Homeodomain Proteins; D009025:Morpholines; D009419:Nerve Tissue Proteins; D016900:Neurofilament Proteins; D018809:Proliferating Cell Nuclear Antigen; D017978:Receptors, Growth Factor; D017475:Receptors, Nerve Growth Factor; D058828:Serotonin 5-HT4 Receptor Agonists; D017366:Serotonin Receptor Agonists; D014157:Transcription Factors; C068313:Ngfr protein, rat; D019009:Proto-Oncogene Proteins c-kit; D020813:Receptor, trkB; C062720:mosapride