General Obstetrics and Gynecology: Gynecology
Uterine innervation after hysterectomy for chronic pelvic pain with, and without, endometriosis

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Objective

Chronic pelvic pain is associated with a wide range of clinical conditions that include endometriosis. The precise cause, mechanisms of pain, and natural history are imprecise. Patterns of uterine innervation have been studied after hysterectomy for chronic pelvic pain with and without endometriosis.

Study design

Tissue blocks were taken from the lower one half of the uterus after hysterectomy for advanced endometriosis (n = 16 specimens; group 1) and for chronic pelvic pain without endometriosis (n = 15 specimens; group 2). The control group consisted of uteri that were removed for painless gynecologic conditions (n = 25 specimens; group 3). Tissue sections from the lower one half of the uterus were stained with anti-S100 to demonstrate patterns of innervation, and nerve fiber profiles were counted by standardized techniques; qualitative differences were also recorded.

Results

In uteri from women with advanced endometriosis, there were increased numbers of nerve fiber profiles compared with control specimens (group 1 vs group 3; P = .0013, Mann Whitney U test). There were also increased numbers of nerve fiber profiles in uteri that were associated with chronic pelvic pain without endometriosis (group 2 vs group 3; P = .04, Mann Whitney U test). There were no differences in nerve fiber count in uteri from groups 1 and 2 (P = .35, Mann Whitney U test). Comparing both groups of uteri with controls (groups 1 and 2 vs 3) demonstrated marked differences in nerve fiber counts (P = .002, Mann Whitney U test). Two distinctive patterns of reinnervation that were observed: disruption of nerve bundles (collateral sprouting with microneuroma formation) and ingrowth around blood vessels (perivascular nerve fiber proliferation). There were increased numbers of microneuromas (groups 1 and 2 vs 3; P = .001, chi-squared test with Yates correction) and perivascular nerve fiber proliferation (groups 1 and 2 vs 3; P = .008, chi-squared test with Yates correction) in the myometrium in chronic pelvic pain with, and without, endometriosis compared with the control group.

Conclusion

Nerve fiber proliferation and other features of reinnervation have been observed in the isthmic regions of uteri that were removed at hysterectomy for chronic pelvic pain with and without endometriosis. There were no quantitative differences between the groups with chronic pelvic pain and endometriosis. These observations provide an alternative explanation for the source of pain and other clinical symptoms in these clinical settings.

Section snippets

Patients

Samples from the lower one half of the uterus of 16 consecutive patients with advanced endometriosis (revised American Fertility Society, grades III-IV) who underwent hysterectomy for endometriosis (group 1; mean age, 41.5 years [range, 27-53 years]; nulliparous, 8/16 samples; multiparous, 8/16 samples) were collected. The diagnosis of endometriosis was confirmed by histologic examination in 14 of 16 specimens. Eight uteri had incidental fibroid tumors, and 2 uteri had mild adenomyosis. Samples

Results

Increased numbers of nerve profiles were observed in the myometrium of the lower half of the uterus in endometriosis (group 1 vs group 3; P = .0013, Mann Whitney U test) and chronic pelvic pain (group 2 vs group 3; P = .04) compared with controls (Table; Figure 1, Figure 2, Figure 3, Figure 4). There were no significant differences in the nerve counts between these 2 groups (group 1 vs group 2; P = .35, Mann Whitney U test).

A comparison of uteri from women with chronic pelvic pain with and

Comment

Nerve fiber proliferation in the lower half of the uterus has been observed in women with chronic pelvic pain with and without endometriosis that may contribute to clinical symptoms in both groups. There were no quantitative differences in nerve counts that suggested a similar cause for chronic pelvic pain, irrespective of the presence of ectopic endometrium. Nerve fiber proliferation was extensive, chaotic, and, in some blocks, asymmetric, affecting one half of the uterus to a greater degree.21

Acknowledgment

We thank Peter Clark for the immunohistochemical studies and Andy Vail for the statistical analysis.

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