Screening the Role of Pronociceptive Molecules in a Rodent Model of Endometriosis Pain

Abstract

Chronic pain is a major symptom in patients with endometriosis, a common gynecologic condition affecting women in their reproductive years. While many pro-algesic substances are produced by endometriosis lesions, experimental evidence supporting their relative roles is still lacking. Furthermore, it is unclear whether these pro-algesic agents directly activate nociceptors to induce endometriosis pain. To determine their relative contribution to pain associated with endometriosis we evaluated the intrathecal administration of oligodeoxynucleotides antisense to mRNA for receptors for three pro-nociceptive mediators known to be produced by ectopic endometrium. Two weeks after the implant of autologous uterine tissue onto the gastrocnemius muscle, local mechanical hyperalgesia was observed in operated rats. Intrathecal antisense oligodeoxynucleotides (AS ODN) targeting mRNA for the interleukin 6 receptor-signaling complex subunit glycoprotein 130 and the NGF tyrosine kinase receptor A (TrkA), but not their mismatch ODNs, reversibly attenuated mechanical hyperalgesia at the implant site. In contrast, intrathecal AS ODN targeting the tumor necrosis factor receptor 1 (TNFR1), at a dose that markedly inhibited intramuscularly injected TNFα had only a small antihyperalgesic effect in this model. These results indicate the relative contribution of pronociceptive mediators produced by ectopic endometrial tissue to endometriosis pain. The experimental approach presented here provides a novel method to evaluate for the differential contribution of mediators produced by other painful lesions as well as endometriosis solutions lesions as targets for novel treatment of pain syndromes. Perspective This article presents evidence for the relative contribution of pro-algesic mediators to primary hyperalgesia displayed by rats submitted to a model of endometriosis pain. This approach can be used to identify potential targets for the treatment of endometriosis pain.

Joint problems arising from lack of repair mechanisms: can cannabinoids help?

“…This is interesting at a number of levels. IL‐6 is known to induce pain (Alvarez and Levine, ) along with MMP3 having a role in matrix turn over, which may diffuse from the synovium into cartilage in parallel to MMP13 (Moore et al ., ). Fukoda et al .…”

Endometriosis: current challenges in modeling a multifactorial disease of unknown etiology

“…These models offered insights into the effects of ectopic endometrial tissue growth [ 55 ], in vitro fertilization, embryo development and implantation, and oviduct transport [ 56 ]. Pain mechanisms [ 57 ], as well as inflammation [ 58 ] and organ adhesion [ 59 ] were also studied in mice. However, one of the major problems of using rodents in endometriosis research is that only superficial lesions can be induced in these animals and those are the simplest and perhaps the least clinically important types of lesion.…”

Chronic pelvic pain in women with endometriosis and uterine myoma (a review)

“…P. Alvarez и соавт. [21] выяснили, что огромную роль в патогенезе боли в первую очередь играют такие медиаторы, как IL-6 и МСР-1, (а не TNF-α), действуя на рецепторы TrkA, TNFR1, рецептор цитокинов 1-го типа (комплекс рецептора IL-6 и gp130).…”