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Relaxin: Its Role in the Pathogenesis of Fibromyalgia

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By Samuel K. Yue, M.D. • • April 16, 2001


Fibromyalgia is a debilitating disorder that is estimated to affect 2% (5 million) of the population of the United States. The ratio of female to male is approximately 9:1. It is also estimated that fibromyalgia costs the U.S. economy 9.2 billion dollars annually.


Symptoms accompanying this disorder include widespread muscular and joint pain, spasm and diffuse tenderness in most areas of the body, unrefreshing sleep, fatigue and emotional distress. The Arthritis Foundation describes fibromyalgia as a form of soft tissue and muscular rheumatism. It is frequently associated with disorders such as irritable bowel, chronic fatigue and myofascial pain syndrome.


Diagnosis of fibromyalgia is made by clinical elimination. Patients with no known diagnosis but with widespread pain, muscle spasm and fatigue of greater than three months duration; examination of specific sites of the body revealing 11 of the 18 sites on both sides of the body are painful on palpation, the diagnosis of fibromyalgia is made. These specific sites are at the base of the occiput, the cervical anterior, the trapezius, the supraspinatus, the second rib, the epicondyle on the elbow region, the greater trochanter, the gluteus and the fat pad on the knee.

Associated Disorders

Chronic fatigue is often associated with fibromyalgia as well as many other disorders. These disorders include irritable bowel and bladder, panic disorder, amnesia disorder, allergic rhinitis, blurred vision, muscle fasciculation, myasthenia, interstitial cystitis, sleep disorder, headache, bruxism, TMJ syndrome, alopecia, thermal regulatory dysfunction, lymphadenalgia, dyspnea, chemical sensitivity, endometriosis, PMS, heart palpitation, photophobia, vertigo, Raynaud's phenomenon and dysmenorrhea. The etiology of fibromyalgia is unclear and unknown, and there is no effective curative treatment. Current therapy is directed primarily to alleviation of symptoms and management of pain.

Current Therapies

Therefore, management using nonprescription medication, prescription anti-inflammatory drugs, injection of local anesthetic agents, physical therapy and exercise all are used to reduce symptoms related to the problems mentioned above. Medications such as tricyclic antidepressants are commonly prescribed to promote deeper sleep, which sometimes reduce symptoms. However, almost all current therapies are limited to reducing the severity of symptoms rather than treating the cause of the symptoms.

Observations about Female Fibromyalgia Patients

Over the course of many years I have observed fibromyalgia patients and have come to some rather interesting observations. Female fibromyalgia patients seem to have increased severity of their symptoms one week before and one week during menstruation on a regular basis. Further, many fibromyalgia patients’ symptoms appear or to be greatly aggravated during menopause between their fourth and fifth decades, or prematurely through surgically induced menopause. One other interesting observation I have made during these years was that many fibromyalgia patients reported remission of their symptoms when they were pregnant, and the return of their S/S almost within one to two months after delivery.

Myofascial pain syndrome

At about the same time, I began to utilize botulinum toxin in many patients with myofascial pain syndrome. I also found that many fibromyalgia patients with cervical neck pain or headaches responded to botulinum toxin injections to the musculature surrounding the cervical neck. This indicated to me that somehow the musculature on these patients is shortened and contracted, and that the tonicity of the muscles must play a part in the pathogenesis of their symptoms.

Discovery of Relaxin

These observations gave me insight to begin searching for any agent or hormone within our body that would have an effect on the collagen of connective tissues. This agent must have effect on the contraction or the shortening of the muscle through the effect on collagen, resulting in spasm and spasticity of the musculature. It was through this search that I came to a little known pregnancy hormone called relaxin which is produced ten times higher during pregnancy in most mammals.

Role of Relaxin

Relaxin has a diverse range of effects, including the production and remodeling of collagen, increase in elasticity and relaxation of muscles, tendons and ligaments during pregnancy, particularly in the pelvis. It is this hormone that is responsible for the remodeling of the pelvic region in preparation for descent of the fetus.

The physiology of relaxin has been well documented in the literature regarding its structure, function and property. It is a polypeptide very similar to insulin and is secreted in females in the ovaries, and in males in the seminal tubules.

Preparation of Relaxin

Relaxin hormone has been prepared from animal form, particularly the pregnant sow, and had been used quite extensively in the 50's and 60's as an agent for shortening of labor, ripening of the cervix and the treatment of scleroderma and peripheral vascular disease. More than three thousand people have been treated with relaxin with various degrees of response to the porcine relaxin. Human form of relaxin has been prepared synthetically by recombinant DNA method and is presently produced by Connetics Corporation in Palo Alto, California.


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