These discoveries were followed by the realization that deeply infiltrating endometriosis (defined by disease infiltration of more than 5 mm, often in the uterosacral ligaments) was more likely to be painful than superficial disease, said Dr. Rapkin. “In some women with endometriosis, the disease we see laparoscopically is really the tip of the iceberg.”
In 2005, landmark studies performed by Karen J. Berkley, PhD, were summarized in a paper coauthored by Dr. Berkley, Dr. Rapkin, and Raymond E. Papka, PhD.13 “In a rodent model where endometriosis was developed by suturing pieces of endometrium in the mesentery, the endometriosis implants developed a vascular supply and a nerve supply. These nerves were not just functioning to govern the dilation and contraction of the blood vessels (in other words the sympathetic type nerves), but these nerves stained for neurotransmitters associated with pain (algesic agents, such as substance P and CGRP),” said Dr. Rapkin. “At UCLA, we acquired tissue from women with endometriosis and analyzed in Dr. Papka’s lab. Those tissues also showed nerves staining for pain-producing chemicals.” Other studies performed worldwide also demonstrated nerve endings with neurotrophic and algesic chemicals in endometriotic tissues. In addition to prostaglandins and cytokines, increased expression of various neuropeptides, neurotrophins, and alterations in ion channels contribute to hypersensitivity and pain.
Q What other chronic pain conditions might women with endometriosis experience?
Overlapping chronic pain conditions are common in women with endometriosis. “There is a very high co-occurrence of interstitial cystitis/painful bladder syndrome,” said Dr. Rapkin. “Irritable bowel syndrome is more common in women with endometriosis, as is vulvodynia. Fibromyalgia, migraine headache, temporo-mandibular joint pain (TMJ), anxiety, and depression also commonly co-occur in women with endometriosis.”
“Two concepts may be relevant to why these overlapping pain conditions develop,” Dr. Rapkin continued. “First, visceral sensitization: If one organ or tissue is inflamed and becomes hyperalgesic then other organs in the adjacent region with shared thoracolumbar and sacral innervation can become sensitized through shared cell bodies in the spinal cord, cross-sensitization in the cord, or at higher regions of the CNS. In addition, visceral somatic conversion occurs, whereby somatic tissues such as muscles and subcutaneous tissues with the same nerve supply as the affected organs become sensitized. This process may explain why abdominal wall and pelvic floor muscles become painful. The involvement of surrounding musculature is an important contributor to the pain in many women with endometriosis.”
“Finally, genetic studies of alterations in genes that encode for chemicals affecting the sensitivity and perception of pain are shedding light on the development of chronic pain. Ultimately these studies will advance our understanding of pain related to endometriosis.”
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