Rogelio Garrido

Gonyautoxin: New Treatment for Healing Acute and Chronic Anal Fissures

PURPOSE:The mayor symptoms of chronic anal fissure are permanent pain, intense pain during defecation that lasts for hours, blood in the stools, and sphincter cramps. It is subsequent to formation of fibrosis infiltrate that leads to an increased anal tone with poor healing tendency. This vicious circle leads to fissure recurrence and chronicity. This study was designed to show the efficacy of gonyautoxin infiltration in healing patients with anal fissures.METHODS:Gonyautoxin is a paralyzing phytotoxin produced by dinoflagellates. Fifty recruited patients received clinical examination, including proctoscopy and questionnaire to evaluate the symptoms. Anorectal manometries were performed before and after toxin injection. Doses of 100 units of gonyautoxin in a volume of 1 ml were infiltrated into both sides of the anal fissure in the internal anal sphincter.RESULTS:Total remission of acute and chronic anal fissures were achieved within 15 and 28 days respectively. Ninety-eight percent of the patients healed before 28 days with a mean time healing of 17.6 ± 9 days. Only one relapsed during 14 months of follow-up. Neither fecal incontinence nor other side effects were observed. All patients showed immediate sphincter relaxation. The maximum anal resting pressures recorded after two minutes decreased to 56.2 ± 12.5 percent of baseline.CONCLUSIONS:Gonyautoxin breaks the vicious circle of pain and spasm that leads to anal fissure. This study proposes gonyautoxin anal sphincter infiltration as safe and effective alternative therapeutic approach to conservative, surgical, and botulinum toxin therapies for anal fissures.

The Gonyautoxin 2/3 epimers reduces anal tone when injected in the anal sphincter of healthy adults

The primary clinical symptom of Paralytic Shellfish Poisoning is acute paralytic illness produced by paralyzing toxins. Paralytic shellfish poison is formed by a mixture of phycotoxins and their toxicity is due to its reversible binding to a receptor site on the voltage-gated sodium channel on excitable cells, thus blocking neuronal transmission. We studied the effect of the gonyautoxin 2/3 epimers by local infiltration in the anal internal sphincter of healthy voluntary adults in order to reduce anal tone. The toxin was injected after prior clinical evaluation, anoscopy and anorectal manometry. Post injection clinical examination, electromyography and anorectal manometry were performed. Resting and voluntary contraction pressures were measured and the anorectal inhibitory and anocortical reflexes were tested by manometry. Blood and urine samples were obtained from each participant, and hemogram, basic metabolic panel, and urinalysis were done both before and one week after the injection. This study shows, for the first time, that gonyautoxin 2/3 reduces the anal tone by relaxing the anal sphincters in 100 % of the participants. Manometric recordings showed a significant decrease in anal maximal voluntary contraction pressure after the toxin injection, dropping to 55.2+/-6.2 % and 47.0+/-6.8% (Mean Value+/-Std.Dev.) of the baseline values at 2 minutes and at 24 hours respectively after the injection. Post-injection electromyography showed that activity of the muscle was abolished. We conclude that local administration of gonyautoxin 2/3 to the anal sphincter produces immediate relaxation and a statistically significant decrease in the anal tone (p <0.001).

Treatment of chronic anal fissure by gonyautoxin

Objective  The use of gonyautoxin has been reported to be safe and effective in healing acute and chronic anal fissures. This study was designed to show better efficacy in healing patients with chronic anal fissure by increasing the frequency of toxin injection.