Susan F Evans1, Yuen H Kwok2, Ann Solterbeck3, Jiajun Liu2, Mark R Hutchinson1,4, M Louise Hull5, Paul E Rolan6. 1. Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia. 2. Faculty of Health Science, University of Adelaide, Adelaide, South Australia, Australia. 3. Statistical Revelations, Melbourne, Victoria, Australia. 4. Australian Research Council Centre of Excellence for Nanoscale BioPhotonics, University of Adelaide, Adelaide, South Australia, Australia. 5. Robinson Research Institute, School or Pediatrics and Reproductive Health, University of Adelaide, Adelaide, South Australia, Australia. 6. School of Medicine, University of Adelaide, Adelaide, South Australia, Australia.
Abstract
PURPOSE: Dysmenorrhea is a common disorder that substantially disrupts the lives of young women. To determine whether there is evidence of activation of the innate immune system in dysmenorrhea and whether the degree of activation may be used as a biomarker for pain, we compared the responsiveness of peripheral blood mononuclear cells (PBMCs) to toll-like receptor (TLR) 2 or 4 stimulation. We also investigated whether this effect is modulated by the use of the oral contraceptive pill (OC). PATIENTS AND METHODS: Fifty-six women aged 16-35 years, with either severe or minimal dysmenorrhea, and use or non-use of the OC, were enrolled. PBMCs were collected on two occasions in a single menstrual cycle: the menstrual phase and the mid-follicular phase. PBMCs were exposed to lipopolysaccharide (LPS), a TLR4 agonist, and PAM3CSK4 (PAM), a TLR2 agonist, and the resulting interleukin-1beta (IL-1β) output was determined. Statistical analysis compared the EC50 between groups as a measure of TLR responsiveness of PBMCs. RESULTS: The key finding following LPS stimulation was a pain effect of dysmenorrhea (p=0.042) that was independent of use or non-use of OC, and independent of day of testing. Women with dysmenorrhea showed a large 2.15-fold (95% CI -4.69, -0.09) increase in IL-1β release when compared with pain-free participants across both days. CONCLUSION: This is the first study to demonstrate an ex vivo immune relationship in women with dysmenorrhea-related pelvic pain. It provides evidence for the potential of immune modulation as a novel pharmacological target for future drug development in the management of dysmenorrhea.
PURPOSE: Dysmenorrhea is a common disorder that substantially disrupts the lives of young women. To determine whether there is evidence of activation of the innate immune system in dysmenorrhea and whether the degree of activation may be used as a biomarker for pain, we compared the responsiveness of peripheral blood mononuclear cells (PBMCs) to toll-like receptor (TLR) 2 or 4 stimulation. We also investigated whether this effect is modulated by the use of the oral contraceptive pill (OC). PATIENTS AND METHODS: Fifty-six women aged 16-35 years, with either severe or minimal dysmenorrhea, and use or non-use of the OC, were enrolled. PBMCs were collected on two occasions in a single menstrual cycle: the menstrual phase and the mid-follicular phase. PBMCs were exposed to lipopolysaccharide (LPS), a TLR4 agonist, and PAM3CSK4 (PAM), a TLR2 agonist, and the resulting interleukin-1beta (IL-1β) output was determined. Statistical analysis compared the EC50 between groups as a measure of TLR responsiveness of PBMCs. RESULTS: The key finding following LPS stimulation was a pain effect of dysmenorrhea (p=0.042) that was independent of use or non-use of OC, and independent of day of testing. Women with dysmenorrhea showed a large 2.15-fold (95% CI -4.69, -0.09) increase in IL-1β release when compared with pain-free participants across both days. CONCLUSION: This is the first study to demonstrate an ex vivo immune relationship in women with dysmenorrhea-related pelvic pain. It provides evidence for the potential of immune modulation as a novel pharmacological target for future drug development in the management of dysmenorrhea.
Authors: Willem Brinkert; Georg Dimcevski; Lars Arendt-Nielsen; Asbjørn M Drewes; Oliver H G Wilder-Smith Journal: Pain Date: 2007-01-25 Impact factor: 6.961
Authors: E Somigliana; P Viganò; B Gaffuri; M Candiani; M Busacca; A M Di Blasio; M Vignali Journal: Am J Reprod Immunol Date: 1996-11 Impact factor: 3.886
Authors: Helen Slater; Markus Paananen; Anne J Smith; Peter O'Sullivan; Andrew M Briggs; Martha Hickey; Jenny Mountain; Jaro Karppinen; Darren Beales Journal: Pain Date: 2015-12 Impact factor: 6.961
Authors: Peter M Grace; Vivianne L Tawfik; Camilla I Svensson; Michael D Burton; Marco L Loggia; Mark R Hutchinson Journal: J Neurosci Date: 2020-11-25 Impact factor: 6.167
Authors: Susan F Evans; Yuen Kwok; Ann Solterbeck; Carmen Pyragius; Mary Louise Hull; Mark R Hutchinson; Paul Rolan Journal: J Pain Res Date: 2021-03-03 Impact factor: 3.133