PMID- 18308859 OWN - NLM STAT- MEDLINE DCOM- 20080522 LR - 20201209 IS - 0193-1857 (Print) IS - 0193-1857 (Linking) VI - 294 IP - 4 DP - 2008 Apr TI - A new possibility for repairing the anal dysfunction by promoting regeneration of the reflex pathways in the enteric nervous system. PG - G1084-93 LID - 10.1152/ajpgi.00345.2007 [doi] AB - 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. FAU - Katsui, Renta AU - Katsui R AD - Dept. of Physiology II, Nara Medical Univ., 840 Shijo-cho, Kashihara 634-8521, Japan. FAU - Kojima, Yu AU - Kojima Y FAU - Kuniyasu, Hiroki AU - Kuniyasu H FAU - Shimizu, Juichiro AU - Shimizu J FAU - Koyama, Fumikazu AU - Koyama F FAU - Fujii, Hisao AU - Fujii H FAU - Nakajima, Yoshiyuki AU - Nakajima Y FAU - Takaki, Miyako AU - Takaki M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20080228 PL - United States TA - Am J Physiol Gastrointest Liver Physiol JT - American journal of physiology. Gastrointestinal and liver physiology JID - 100901227 RN - 0 (Benzamides) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Distal-less homeobox proteins) RN - 0 (Gastrointestinal Agents) RN - 0 (Homeodomain Proteins) RN - 0 (Morpholines) RN - 0 (Nerve Tissue Proteins) RN - 0 (Neurofilament Proteins) RN - 0 (Proliferating Cell Nuclear Antigen) RN - 0 (Receptors, Growth Factor) RN - 0 (Receptors, Nerve Growth Factor) RN - 0 (Serotonin 5-HT4 Receptor Agonists) RN - 0 (Serotonin Receptor Agonists) RN - 0 (Transcription Factors) RN - 136958-07-1 (Ngfr protein, rat) RN - EC 2.7.10.1 (Proto-Oncogene Proteins c-kit) RN - EC 2.7.10.1 (Receptor, trkB) RN - I8MFJ1C0BY (mosapride) SB - IM MH - Anal Canal/*innervation/physiopathology/surgery MH - Anastomosis, Surgical MH - Animals MH - Benzamides/*pharmacology MH - Brain-Derived Neurotrophic Factor/pharmacology MH - Cell Proliferation MH - *Defecation/drug effects MH - Dose-Response Relationship, Drug MH - Enteric Nervous System/drug effects/metabolism/*physiopathology/surgery MH - Gastrointestinal Agents/pharmacology MH - Guinea Pigs MH - Homeodomain Proteins/metabolism MH - Immunohistochemistry MH - Male MH - Morpholines/*pharmacology MH - *Nerve Regeneration/drug effects MH - Nerve Tissue Proteins MH - Neurofilament Proteins/metabolism MH - *Neuronal Plasticity/drug effects MH - Pressure MH - Proliferating Cell Nuclear Antigen/metabolism MH - Proto-Oncogene Proteins c-kit/metabolism MH - Receptor, trkB/metabolism MH - Receptors, Growth Factor MH - Receptors, Nerve Growth Factor/metabolism MH - Recovery of Function MH - Rectum/*innervation/physiopathology/surgery MH - *Reflex/drug effects MH - Serotonin 5-HT4 Receptor Agonists MH - Serotonin Receptor Agonists/pharmacology MH - Time Factors MH - Transcription Factors/metabolism EDAT- 2008/03/01 09:00 MHDA- 2008/05/23 09:00 CRDT- 2008/03/01 09:00 PHST- 2008/03/01 09:00 [pubmed] PHST- 2008/05/23 09:00 [medline] PHST- 2008/03/01 09:00 [entrez] AID - 00345.2007 [pii] AID - 10.1152/ajpgi.00345.2007 [doi] PST - ppublish SO - Am J Physiol Gastrointest Liver Physiol. 2008 Apr;294(4):G1084-93. doi: 10.1152/ajpgi.00345.2007. Epub 2008 Feb 28.