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

Abstract

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.

Behavioural and neural responses to aversive visceral stimuli in women with primary dysmenorrhoea

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A model for radiating leg pain of endometriosis

“…Here we report initial observations of a model, in which a section of uterus was autotransplanted to the sciatic nerve. A similar model has recently been published which demonstrated behavioral hypersensitivities and increased afferent drive (Chen et al, 2015). …”

Perineural invasion in endometriotic lesions contributes to endometriosis-associated pain

“…It seems that nerve compression and distortion or damage by endometrial cells may be a crucial mechanism of inflammation around the lesion. 33 , 34 However, inflammatory factors can inversely facilitate the invasive behavior of endometrial cells to endometriosis-associated nerve fibers. The invasion of the ectopic implant triggers the formation of a complicated interaction net.…”