Estrous changes in vaginal nociception in a rat model of endometriosis

Cason, Angie M.; Samuelsen, Chad L.; Berkley, Karen J.

doi:10.1016/s0018-506x(03)00121-1

Cited by 83 publications

(112 citation statements)

References 27 publications

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“…Regardless of the mechanisms by which the cysts become innervated, the demonstration of a robust sensory innervation by C fibers raises the distinct possibility that this innervation contributes to both the vaginal hyperalgesia and the reduced fertility that occur in this rat model (9,10), probably via central effects, as follows. The cysts are known to contain proinflammatory cytokines, prostaglandins, and other neuroactive agents (8,10) that could readily activate the CGRP-and SP-positive C-fiber nociceptive afferents (32,33) found here to be located in the cyst's epithelium.…”

Section: Discussionmentioning

confidence: 99%

“…The cysts are known to contain proinflammatory cytokines, prostaglandins, and other neuroactive agents (8,10) that could readily activate the CGRP-and SP-positive C-fiber nociceptive afferents (32,33) found here to be located in the cyst's epithelium. Although the route by which the information conveyed by these activated fibers enters the CNS is not yet known, given the location of the cysts in the upper abdomen, it is most likely that this route will be found to include the splanchnic nerve, with fibers traveling in the superior mesenteric, inferior mesenteric, and celiac ganglia to the lower thoracic͞upper lumbar segments (9,11). Such activated input to the spinal cord could then influence the sensitivity of neurons in the lower lumbar and upper sacral segments that receive vaginal input (9,11,33) via the extensive communication known to exist between the two sets of segments (34), a process which has been called viscero-visceral referred hyperalgesia (35).…”

Section: Discussionmentioning

confidence: 99%

“…Rats were killed when cysts were known to be fully grown (Ϸ7.5 weeks postsurgery; ref. 8), when they were in proestrus, the estrous stage in which ovarian hormonal levels are highest and the severity of vaginal hyperalgesia is greatest (9). They were anesthetized with urethane (1.2 g͞kg, i.p.)…”

Section: Surgical Procedures (Endo)mentioning

confidence: 99%

“…Like women with ENDO, rats with cysts (but not the controls) display reduced fertility (8). They also display one of the symptoms of increased pelvic pain in women, that is, vaginal hyperalgesia (9). Furthermore, the ectopic cysts in rats bear clear similarities to human ectopic endometriotic growths.…”

mentioning

confidence: 98%

“…Specifically, the cysts in rats and the growths in women respond similarly to steroids, and the cysts synthesize or induce synthesis by cultured peritoneal cells of many of the same abnormal substances found in the ectopic endometrial growths and peritoneal fluid of women with ENDO (10). This rat model, therefore, seems suitable for investigating new ideas concerning mechanisms underlying signs and symptoms of ENDO (9,10). Accordingly, here we tested the hypothesis that the cysts in this rat model develop their own nerve supply and then determined whether that supply included both sensory and sympathetic efferent fibers.…”

mentioning

confidence: 99%

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Innervation of ectopic endometrium in a rat model of endometriosis

Berkley

Dmitrieva

Curtis

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

194

161

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Endometriosis (ENDO) is a disorder in which vascularized growths of endometrial tissue occur outside the uterus. Its symptoms include reduced fertility and severe pelvic pain. Mechanisms that maintain the ectopic growths and evoke symptoms are poorly understood. One factor not yet considered is that the ectopic growths develop their own innervation. Here, we tested the hypothesis that the growths develop both an autonomic and a sensory innervation. We used a rat model of surgically induced ENDO whose growths mimic those in women. Furthermore, similar to women with ENDO, such rats exhibit reduced fertility and increased pelvic nociception. The ENDO was induced by autotransplanting, on mesenteric cascade arteries, small pieces of uterus that formed vascularized cysts. The cysts and healthy uterus were harvested from proestrous rats and immunostained using the pan-neuronal marker PGP9.5 and specific markers for calcitonin gene-related peptide (CGRP) (sensory C and A␦ fibers), substance P (SP) (sensory C and A␦ fibers) and vesicular monoamine transporter (sympathetic fibers). Cysts (like the uterus) were robustly innervated, with many PGP9.5-stained neurites accompanying blood vessels and extending into nearby luminal epithelial layers. CGRP-, SP-, and vesicular monoamine transporter-immunostained neurites also were observed, with CGRP and SP neurites extending the furthest into the cyst lining. These results demonstrate that ectopic endometrial growths develop an autonomic and sensory innervation. This innervation could contribute not only to symptoms associated with ENDO but also to maintenance of the ectopic growths.uterus ͉ fertility ͉ pain ͉ transplant ͉ neuropeptides

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Surgical Procedures (Endo)mentioning

confidence: 99%

mentioning

confidence: 98%

mentioning

confidence: 99%

See 3 more Smart Citations

Innervation of ectopic endometrium in a rat model of endometriosis

Berkley

Dmitrieva

Curtis

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

194

161

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Neuroendocrine Aspects of Endometriosis‐Associated Pain

Stratton

Berkley

2011

Endometriosis

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Sciatic endometriosis induces mechanical hypersensitivity, segmental nerve damage, and robust local inflammation in rats

Chen

Xie

Strong

et al. 2015

European Journal of Pain

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Background Endometriosis is a common cause of pain including radicular pain. Ectopic endometrial tissue may directly affect peripheral nerves including the sciatic, which has not been modelled in animals. Methods We developed a rat model for sciatic endometriosis by grafting a piece of autologous uterine tissue around the sciatic nerve. Control animals underwent a similar surgery but received a graft of pelvic fat tissue. Results The uterine grafts survived and developed fluid filled cysts; the adjacent nerve showed signs of swelling and damage. Mechanical and cold hypersensitivity and allodynia of the ipsilateral hindpaw developed gradually over the first two weeks after the surgery, peaked at 2 to 5 weeks, and was almost resolved by 7 weeks. Control animals showed only minor changes in these pain behaviors. Histological signs of inflammation in the uterine graft and in the adjacent nerve were observed at 3 weeks but were resolving by 7 weeks. In vivo fiber recording showed increased spontaneous activity, especially of C fibers, in sciatic nerve proximal to the uterine graft. Several pro-inflammatory cytokines including interluekin-18, VEGF, fractalkine, and MIP-1α, were elevated in the uterine graft plus sciatic nerve samples, compared to samples from normal nerve or nerve plus fat graft. Growth associated protein 43 (GAP43), a marker of regenerating nerve fibers, was observed in the adjacent sciatic nerve as well as in the uterine graft. Conclusions This model shared many features with other rat models of endometriosis, but also had some unique features more closely related to neuropathic pain models.

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Estrous changes in vaginal nociception in a rat model of endometriosis

Cited by 83 publications

References 27 publications

Innervation of ectopic endometrium in a rat model of endometriosis

Innervation of ectopic endometrium in a rat model of endometriosis

Neuroendocrine Aspects of Endometriosis‐Associated Pain

Sciatic endometriosis induces mechanical hypersensitivity, segmental nerve damage, and robust local inflammation in rats

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