Background & Aims
It is well established that the prevalence rate of musculoskeletal pain
is significantly higher in women with respect to males, with an even greater onset of chronic
conditions [1]. It is recently reported that fascia can be a possible source of pain: if the
connective tissue is altered, the behaviour of the fascial tissue and the underlying muscle may
become compromised causing myofascial pain. Sex hormone disorders can dysregulate the
fascial tissue: the comprehension of this mechanism is an important step for understanding
gender differences in myofascial pain, helping clinicians to diagnose and treat patients [2].
Methods
Immunohistochemical and molecular investigations (real-time PCR analysis) of
relaxin receptor 1 (RXFP1) and estrogen receptor-alpha (ER?) localization were carried out
on sample of human fascia collected from 8 volunteers patients during orthopedic surgery (all
females, between 42 and 70 yrs, divided into pre- and post-menopausal groups), and in
fibroblasts isolated from deep fascia, to examine both protein and RNA expression levels.
Moreover, an immunocytochemical analysis of collagen-I, collagen-III and fibrillin were
carried out on fibroblasts isolated from human fascia lata after in vitro treatment with various
levels of sex hormones ?-estradiol and/or relaxin-1, according to the phases of a woman’s
period (follicular, periovulatory, luteal, post-menopausal phases and pregnancy).
Results
RXFP1 and ER? are expressed in all the human fascial districts examined and in
fascial fibroblasts culture cells, to a lesser degree in the post-menopausal with respect to the
pre-menopausal women [3]. The cells of the fascia can moreover modulate the synthesis of
extracellular matrix components depending on hormone levels: when ?-estradiol levels are
low, fascial tissue becomes enriched in collagen-I (from 5.2% of control sample to 8.4%),
with a parallel decrease in collagen-III (from 2.4% to 1.5%) and elastic fibres (from 0.5% to
0.2%) [4]. Consequently, the tissue becomes less elastic and more rigid, something that
normally occurs during menopause. Conversely, when hormone levels are high, as during the
ovulatory peak or during pregnancy, the opposite takes place: collagen-III rises to 6.8%
during ovulation and 6.7% during pregnancy as does Fibrillin-1 (from 0.2% in menopause to
3.6% during pregnancy) while collagen-I falls to 1.9% [4]. The result is softer, more elastic
tissue.
Conclusions
These results highlight how hormonal disorders in women can dysregulate the
extracellular matrix synthesis, modifying the properties of tissue and evoking the
sensitization of fascial nociceptors. These results work in parallel with our findings of a tissue
modification with the aging, in which occurs a decrease of sex hormones: with aging we
demonstrated an accumulation of collagen I and a parallel reduction of hyaluronan and
elastic fibers [5].
Further studies on multifactorial effects of sex hormones on fasciae and pain mechanisms
will permit to correlate any dysfunctions in hormonal levels linked to pathologies, ageing and
period of the cycle, to the onset of myofascial pain, thus making it possible to find out a
targeted gender therapy.
References
1. Ceccarelli I, Bioletti L, Peparini S, Solomita E, Ricci C, Casini I, Miceli E, Aloisi AM.
Estrogens and phytoestrogens in body functions. Neurosci Biobehav Rev. 2022;132:648-
663. doi: 10.1016/j.neubiorev.2021.12.007.
2. Fede C, Pirri C, De Caro R, Stecco C. Myofascial pain in females and personalized care:
The key role played by sex hormones. Eur J Pain. 2022;26(4):939-940. doi:
10.1002/ejp.1920.
3. Fede C, Albertin G, Petrelli L, Sfriso MM, Biz C, De Caro R, Stecco C. Hormone receptor
expression in human fascial tissue. Eur J Histochem. 2016;60(4):2710. doi:
10.4081/ejh.2016.2710.
4. Fede C, Pirri C, Fan C, Albertin G, Porzionato A, Macchi V, De Caro R, Stecco C.
Sensitivity of the fasciae to sex hormone levels: Modulation of collagen-I, collagen-III and
fibrillin production. PLoS One. 2019;14(9):e0223195.
5. Fede C, Fan C, Pirri C, Petrelli L, Biz C, Porzionato A, Macchi V, De Caro R, Stecco C.
The Effects of Aging on the Intramuscular Connective Tissue. Int J Mol Sci. 2022 Sep
21;23(19):11061. doi: 10.3390/ijms231911061.
Presenting Author
Carla Stecco
Poster Authors
Topics
- Gender/Sex Differences