Impact of surgical excision of lesions on pain in a rat model of endometriosis

Abstract

Background Chronic pain is the most common and disabling feature of endometriosis. Surgical excision of endometriosis lesions provides relief but pain relapse is common. Studies in a preclinical model of endometriosis might help to unravel the role of the ectopic lesions as the source of pain. Thus, we evaluated the impact of lesion excision on mechanical hyperalgesia in a preclinical model of endometriosis pain. Methods Endometriosis was induced by implanting autologous uterine tissue onto the gastrocnemius muscle. Surgical excision or aspiration drainage of the cystic lesion was performed at different times post-implant and mechanical nociceptive thresholds assessed at the site of the lesion. Results Lesions at 2, 8 and 16 weeks post-implant, produced mechanical hyperalgesia of similar magnitude (n = 6/group). Excision of lesions (n = 6/group) produced a longer inhibition, with a magnitude and time-course depending on the timing of excision. Excision at 2 and 8 weeks produced a rapid onset marked attenuation of hyperalgesia, which returned to pre-excision values by postsurgical week 3. In contrast, excision of the lesion at 16 weeks produced a peak of inhibition of hyperalgesia 2 weeks post-excision, but then the inhibition was sustained. Aspiration of fluid from cysts in the lesions briefly attenuated mechanical hyperalgesia (n = 6/group). Conclusions In this preclinical model we demonstrate that endometriosis pain is alleviated by surgical excision of the ectopic lesion or drainage of its cysts, providing support for the clinical observation that endometriosis pain is dependent on the ongoing presence of the lesions.

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

“…This may be a primary difference between our model of sciatic endometriosis and other rat endometriosis models: the primary cause of pain as measured by hindpaw testing may be essentially neuropathic. This could account for the faster resolution of the pain compared to the gastrocnemius muscle model, in which mechanical pain is undiminished at 16 weeks (Alvarez et al, 2015). In that model, the implant itself is mechanically stimulated whereas in our study the heel region innervated by the affected nerve was tested.…”

“…Normalized pain behaviors were also observed following implant removal in the gastrocnemius muscle model, although only a transient effect was observed when removal was performed at earlier time points (at 2 or 8 weeks in this much longer lasting model). One suggested explanation for the transience was the difficulty in removing all of the endometrial and stromal cells, which invade the muscle in this model (Alvarez et al, 2015). In contrast, in our model there was no infiltration of the adjacent nerve by endometrial cells, perhaps facilitating a more complete removal.…”

Research Priorities for Endometriosis: Recommendations From a Global Consortium of Investigators in Endometriosis

“…A rat model has been developed in which endometrial tissue is transplanted to the gastrocnemius muscle; this has subsequently been used to explore the role of leptin in estrogen-dependent chronic pain. [103][104][105] Five recommendations on endometriosis-related pain were unchanged from 2011, whereas 2 were either no longer relevant or superseded.…”

Prostaglandin levels, vaginal innervation, and cyst innervation as peripheral contributors to endometriosis-associated vaginal hyperalgesia in rodents

“…Further, similar to women, the amount of ectopic growth in endometriosis rats fails to correlate with symptom presence and pain severity; however, ectopic growth excision can provide long-term relief of painful symptoms (Alvarez et al, 2014; McAllister et al, 2009) suggesting some aspect of the growth contributes to the pain. One possibility is that the growth's sprouted sensory and sympathetic nerve supply opens a two-way line of communication between the growths and CNS that is capable of generating pain (Stratton and Berkley, 2011).…”