Estrogenic impregnation alters pain expression: analysis through functional neuropeptidomics in a surgical rat model of osteoarthritis

• Published in: Naunyn-Schmiedeberg's archives of pharmacology 2022-06, Vol.395 (6), p.703-715
• Main Authors: Keita-Alassane, Sokhna, Otis, Colombe, Bouet, Emilie, Guillot, Martin, Frezier, Marilyn, Delsart, Aliénor, Moreau, Maxim, Bédard, Agathe, Gaumond, Isabelle, Pelletier, Jean-Pierre, Martel-Pelletier, Johanne, Beaudry, Francis, Lussier, Bertrand, Lecomte, Roger, Marchand, Serge, Troncy, Eric
• Format: Article
• Language: English
• Subjects: 17β-Estradiol; Analgesics; Animals; Arthritis; Biomedical and Life Sciences; Biomedicine; Body weight; Bradykinin; Calcitonin; Calcitonin gene-related peptide; Calcitonin Gene-Related Peptide - metabolism; Dimorphism; Dynorphin; Estradiol - pharmacology; Estrogens; Female; High-performance liquid chromatography; Mass spectroscopy; Neuropeptides; Neurosciences; Original Article; Osteoarthritis; Osteoarthritis - drug therapy; Ovariectomy; Pain - metabolism; Pain perception; Pharmacology/Toxicology; Placebos; Prospective Studies; Rats; Rats, Sprague-Dawley; Rodents; Somatostatin; Substance P; Substance P - metabolism; Xenoestrogens
• ISSN: 0028-1298; 1432-1912
• DOI: 10.1007/s00210-022-02231-5

Purpose Several observational studies suggest that estrogens could bias pain perception. To evaluate the influence of estrogenic impregnation on pain expression, a prospective, randomized, controlled, blinded study was conducted in a Sprague–Dawley rat model of surgically induced osteoarthritis (OA). Methods Female rats were ovariectomized and pre-emptive 17β-estradiol (0.025 mg, 90-day release time) or placebo pellets were installed subcutaneously during the OVX procedures. Thirty-five days after, OA was surgically induced on both 17β-estradiol (OA-E) and placebo (OA-P) groups. Mechanical hypersensitivity was assessed by static weight-bearing (SWB) and paw withdrawal threshold (PWT) tests. Mass spectrometry coupled with high-performance liquid chromatography (HPLC–MS) was performed to quantify the spinal pronociceptive neuropeptides substance P (SP), calcitonin gene-related peptide (CGRP), bradykinin (BK), somatostatin (SST), and dynorphin-A (Dyn-A). Results Compared to control, ovariectomized rats presented higher SP ( P  = 0.009) and CGRP ( P  = 0.017) concentrations. OA induction increased the spinal level of SP (+ 33%, P