Anal fissure (or fissure-in-ano), anal ulcer, acute hemorrhoidal disease, and levator spasm (proctalgia fugax) are common, benign conditions of the anal canal which affect men and women. An anal fissure or ulcer is a tear or ulcer of the mucosa or lining tissue of the distal anal canal. An anal fissure/ulcer can be associated with other systemic or local diseases, but it is more frequently present as an isolated finding. The typical, idiopathic fissure or ulcer is confined to the anal mucosa, and usually lies in the posterior midline, distal to the dentate line. The person with an anal fissure or ulcer suffers from anal pain and bleeding, more pronounced during and after bowel movements.
Hemorrhoids are specialized vascular areas lying subjacent to the anal mucosa. Symptomatic hemorrhoidal disease is manifest by bleeding, thrombosis or prolapse of the hemorrhoidal tissues. Men and women are affected. Most commonly, internal hemorrhoidal tissue bulges into the anal canal during defecation causing bleeding. As the tissue enlarges, prolapse pain, thrombosis, and bleeding can ensue. Thrombosis of internal or external hemorrhoids is another cause of pain and bleeding.
Levator spasm (or proctalgia fugax) is a condition of unknown etiology affecting women more frequently than men. This syndrome is characterized by spasticity of the levator ani muscle, a portion of the anal sphincter complex. The patient suffering from levator spasm complains of severe, episodic rectal pain. Physical exam may reveal spasm of the puborectalis muscle. Pain may be reproduced by direct pressure on this muscle. Bleeding is not associated with this condition.
The underlying causes of these problems are poorly understood. However, all of these disorders are associated with a relative or absolute degree of anal sphincter hypertonicity. In the case of anal fissure/ulcer the abnormality appears to be an as yet unidentified problem of the internal and sphincter muscle. The internal sphincter is a specialized, involuntary muscle arising from the inner circular muscular layer of the rectum. Intra-anal pressure measurements obtained from people suffering from typical anal fissure/ulcer disease show an exaggerated pressure response to a variety of stimuli. The abnormally high intra-anal pressure is generated by the internal sphincter muscle. The abnormally elevated intra-anal pressure is responsible for non-healing of the fissure/ulcer and the associated pain.
An abnormal pressure response in the anal canal has also been observed in people suffering from symptomatic hemorrhoidal disease. Elevated intra-anal pressures may be a major etiologic factor in the development of this condition. It is postulated that the pain associated with acute hemorrhoidal disease is caused in part by spasm of the internal anal sphincter muscle. Similarly, the pain associated with levator spasm is induced by the muscle spasm itself.
Various therapies have been devised to treat these problems. Typical, non-surgical therapy includes bulk laxatives and sitz baths. Sitz baths are helpful because they induce relaxation of the anal sphincter mechanism. Topical anal therapy is used to promote healing, relieve pain, and reduce swelling and inflammation. Many preparations have been tried, including those containing local anesthetics, corticosteroids, astringents, and other agents. None of these preparations adequately addresses the underlying problem of sphincter spasm. Consequently, none has been show conclusively to favorably alter the time course to healing or to reliably ameliorate associated pain.
Those cases of anal fissure/ulcer or hemorrhoids recalcitrant to medical therapy are often referred for surgical treatment. In keeping with the proposed etiology of anal fissure/ulcer, the current standard surgical procedure for treatment of anal fissure is lateral internal anal sphincterotomy. In this procedure, the internal anal sphincter muscle is partially cut, thereby reducing the intra-anal pressure. The lowered pressure allows the fissure/ulcer to heal and also relieves the associated pain. Surgical hemorrhoidectomy removes the redundant hemorrhoidal tissue. Many surgeons will perform concomitant limited internal anal sphincterotomy to lower anal canal pressure. There is no successful surgical treatment for levator spasm.
Over the past five years a third component of the autonomic nervous system, the enteric nervous system (ENS), has been described and elucidated. This neural network innervates the gut continuously from esophagus to anus. It is composed of enteric neurons and the processes of extrinsic efferent and afferent neurons of the traditional autonomic system. This system regulates the motor and secretory function of the gut.
The most remarkably feature of the ENS is the diversity of chemical messengers that enteric neurons contain and release. In addition to acetylcholine and norepinephrine, various peptide and non-peptide substances have been identified which appear to function as neurotransmitters. Most recently, nitric oxide (NO) has been identified as an inhibitory transmitter to muscle. Rattan, Chakder, O'Kelly, and others have shown that NO mediates the anorectal inhibitory reflex in animals and man. See, Rattan et al., S. Nitric oxide pathway in rectonal inhibitory reflex of opossum internal anal sphincter, Gastroenterology 103:43-50, 1992; Chakder et al., Release of nitric oxide by activation of nonadrenergic noncholinergic neurons of internal anal sphincter, Am. J. Physiol. 264:G7-12, 1993; and O'Kelly, et al., Nerve mediated relaxation of the human internal anal sphincter: The role of nitric oxide. Gut 34:689-693, 1994, each of which is incorporated herein by reference.
Organic nitrates such as nitroglycerin (the trinitrate, NTG), isosorbide dinitrate, isosorbide mononitrate, erythrityl tetranitrate, and others have been used for decades in the clinical setting of angina pectoris. These agents act as physiologic nitric oxide donors. The use of organic nitrates has not been previously proposed for the treatment of anal disease.
Corticosteroids such as hydrocortisone, have been used for various benign anal disorders for many years. Studies of the effectiveness of this treatment have shown some benefit, but not in a reproducible or significant fashion. It has not been heretofore known to use hydrocortisone in combination with organic nitrates for treatment of anal diseases.
Topical anesthetics such as dibucaine, lidocaine, pramoxine, and others have been used for treatment of anal pain. It has not been heretofore known to use topical anesthetics in combination with organic nitrates for treatment of anal diseases.