Submitted on July 28, 2007
Accepted on February 27, 2008
A new possibility for repairing the anal dysfunction by promoting regeneration of the reflex pathways in the enteric nervous system
Renta Katsui1, Yu Kojima2, Hiroki Kuniyasu3, Juichiro Shimizu1, Fumikazu Koyama4, Hisao Fujii4, Yoshiyuki Nakajima4, and Miyako Takaki1*
1 Department of Physiology II, Nara Medical University, Kashihara, Nara, Japan
2 Departments of Physiology II, Nara Medical University, Kashihara, Nara, Japan
3 Department of Molecular Pathology, Nara Medical University, Kashihara, Nara, Japan
4 Department of Surgery, Nara Medical University, Kashihara, Nara, Japan
* To whom correspondence should be addressed. E-mail: mtakaki{at}naramed-u.ac.jp.
Moderate rectal distension elicits rectal (R-R) reflex contractions and simultaneous internal anal sphincter (R-IAS) 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 using the plasticity of enteric nervous pathways. Experiments were performed in anesthetized guinea pigs with ethyl carbamate. The rectum 30 mm oral from 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-HT4 receptor agonist, mosapride (0.5 and 1.0 mg/kg) significantly (P < 0.01) enhanced the recovered defecation reflex eight weeks after surgery. Two weeks after the local treatment with brain-derived neurotrophic factor (BDNF: 10-6 g/ml) at the rectal anastomotic site, the R-IAS 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.
