Saturday, April 5, 2014

Nerve fibers in endo pts (new way to diagnose??)

We have talked before of nerve generation in endometriosis and it's role in pain (see and the summary in the study below). In 2009, two small studies demonstrated that the density of nerve fibers (ie amount) was greater in the endometrium of endometriosis patients than of women without endometriosis. They proposed that an endometrial biopsy could be a potential diagnostic tool to detect if endometriosis could be present without having to do surgery (still would need surgery to treat).

"Pain generation in EM is an intricate interplay of several factors such as the endometriotic lesions themselves and the pain-mediating substances, nerve fibres and cytokine-releasing immune cells such as macrophages. These interactions seem to induce a neurogenic inflammatory process. Recently published data demonstrated an increased peptidergic and decreased noradrenergic nerve fibre density in peritoneal lesions. These data could be substantiated by in vitro analyses demonstrating that the peritoneal fluids of patients suffering from EM induced an enhanced sprouting of sensory neurites from chicken dorsal root ganglia and decreased neurite outgrowth from sympathetic ganglia. These findings might be directly involved in the perpetuation of inflammation and pain. Furthermore, the evidence of EM-associated smooth muscle-like cells seems another important factor in pain generation. The peritoneal endometriotic lesion leads to reactions in the surrounding tissue and, therefore, is larger than generally believed. The identification of EM-associated nerve fibres and smooth muscle-like cells fuel discussions on the mechanisms of pain generation in EM, and may present new targets for innovative treatments."

"In a separate study also published online in Human Reproduction, another research group from Belgium and Hungary has found that the density of nerve fibres in the endometrium was about 14 times higher in women with endometriosis than in healthy women, and that using specific markers to identify the presence of nerve fibres could predict with nearly 100% accuracy the presence of minimal to mild endometriosis/

In the first study, led by Professor Ian S. Fraser, head of the Queen Elizabeth II Research Institute for Mothers and Infants at the University of Sydney and Dr Moamar Al-Jefout, assistant professor in reproductive medicine at Mu'tah University, researchers took endometrial biopsies from 99 women who had consulted doctors about pelvic pain, infertility or both and who were undergoing laparoscopy for the condition.

The results from the endometrial biopsies were compared with the results of the laparoscopies, and the researchers found that in 64 women who had endometriosis confirmed by laparoscopy, all but one tested positive for the presence of nerve fibres in the endometrial biopsy. In the 35 women who were found not to have endometriosis by laparoscopy, no nerve fibres were found in 29 of the endometrial biopsies. In the other six cases, the biopsy found there were nerve fibres present; three of these women had severely painful periods and painful sex, and also a history of infertility, and of the other three, one had adhesions that were considered too slight to be endometriosis, while the other had a previous history of endometriosis.
Women with endometriosis and painful symptoms had significantly higher nerve fibre density in comparison with women with infertility but no pain (2.3 nerve fibres per mm2 compared to 0.8 per mm2 respectively). The mean average of nerve fibre density in the women with a laparoscopic diagnosis of endometriosis was 2.7 per mm2.
The study showed that testing endometrial biopsies for the presence of nerve fibres was able to diagnose endometriosis with 83% specificity (the proportion of negative cases of endometriosis correctly identified) and 98% sensitivity (proportion of positive cases correctly identified). This double blind study confirmed the results of a pilot study published in 2007 by the same group.
Dr Al-Jefout said: "This study has shown that testing for nerve fibres in endometrial biopsies is a valid and highly accurate diagnostic test for endometriosis. This test is probably as accurate as assessment via laparoscopy, the current gold standard, especially as it is unclear how often endometriosis is overlooked, even by experienced gynaecologists. Endometrial biopsy is clearly less invasive than laparoscopy, and this test could help to reduce the current lengthy delay in diagnosis of the condition, as well as allowing more effective planning for formal surgical or long-term medical management. It may be particularly helpful in cases of infertility....

In the second study, led by Professor Thomas D'Hooghe, coordinator of the University of Leuven Fertility Centre (Belgium), researchers looked at 40 endometrial samples, half taken from women with minimal to mild endometriosis diagnosed by laparoscopy and histology (microscopic examination of tissue), and half from women without the condition. They analysed the tissues for several markers indicating the presence of four types of nerve fibres (sensory C, A∂, adrenergic and cholinergic nerve fibres).

Dr Attila Bokor, a doctoral fellow at the University of Leuven, who did the study as part of his PhD project said: "We observed nerve fibres in the endometrial samples of ninety percent (18 out of 20) of the women with endometriosis. The density varied throughout the samples, with few specimens showing counts above 30 per mm2, and with most between 0 and 10 per mm2. None, or very few, nerve fibres, were detected in any of the samples from women without endometriosis. The density of the small nerve fibres was about 14 times higher in endometrium from patients with minimal to mild endometriosis when compared with women with a normal pelvis."
Prof D'Hooghe said: "Our data show that the combination of three different neural markers increases the sensitivity, specificity and diagnostic accuracy of this method of testing for endometriosis. The test diagnosed endometriosis with 95% sensitivity and 100% specificity."
Dr Bokor and the team of Prof D'Hooghe will do a blinded validation study in September 2009 to confirm the results of their research. "If this confirms our findings, we believe our research can be a solid base for a simple, reliable and relatively cheap method for non-invasive diagnosis of minimal and mild endometriosis, since trans-cervical endometrium sampling and immunohistochemical analysis are routine gynaecological and pathological procedures. Our research programme is also aimed at discovering new biomarkers that can enable a blood test for endometriosis to be developed," said Prof D'Hooghe."

Story Source:
The above story is based on materials provided by European Society for Human Reproduction and Embryology. Note: Materials may be edited for content and length."

 SO I"m wondering since patients with endometriosis have nerve fibers found in their endo lesions and higher density of nerves in their endometrium, then could the inflammatory condition created by endo be causing more nerve growth in other areas it's close to? Thereby, playing a role in creating more pain for things like IC, making PFD worse, etc?