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Procedure no significant difference in outcomes between open and closed sphincterotomies Radial incision in anoderm that exposes internal sphincter muscle Distal segment of internal anal sphincter divided for length of anal fissure Wound left open or primarily closure Closed LIS: insert narrow-bladed scalpel directly into intersphincteric groove and divide internal sphincter lateral to medial toward surgeons finger within anal canal Superior to topical nitrates, calcium channel blockers, or botulinum toxin Complications: fecal incontinence (8 30%, usually self-resolves in 30 days) Contraindications: Crohn disease, ulcerative colitis, women of childbearing age, prior obstetrical injury, history of incontinence, sphincter dysfunction Relevant Information Anal fissure locations Posterior midline (73%) most common location Anterior midline Second most common location More common in women Atypical fissure: lateral fissure or multiple fissures Requires more comprehensive evaluation due to association with other diagnoses Differential diagnosis Crohn disease Anal cancer Tuberculosis HIV Syphilis Herpes Leukemia Dentate line Lies midpoint in the anal canal Proximal: longitudinal folds of columnar epithelium (columns of Morgagni) Distal: smooth squamous epithelium (anoderm) Anal verge: where anal canal connects to the outside skin at the anus Complications Bleeding Pain Infection Incontinence Fistula formation Differential Diagnoses Hemorrhoids, external Perianal abscess Sexually transmitted infections Inflammatory bowel disease Tuberculosis Resources American Society of Colon and Rectal Surgeons

PMID 18640588

So a lower level is better

This non-peptide mechanism, elucidated through cryo-electron microscopy and published in the Proceedings of the National Academy of Sciences in 2020, overturned decades of pharmacological dogma that class B GPCRs could only be meaningfully activated by peptide ligands

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