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

Abstract

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 < 0.020) and decreased the release of BK (- 20%, (P < 0.037)). The OA-E rats at functional assessment put more % body weight on the affected hind limb than OA-P rats at D7 (P = 0.027) and D56 (P = 0.033), and showed higher PWT at D56 (P = 0.009), suggesting an analgesic and anti-allodynic effect of 17β-estradiol. Interestingly, the 17β-estradiol treatment counteracted the increase of spinal concentration of Dyn-A (P < 0.016) and CGRP (P < 0.018).

CONCLUSION:

These results clearly indicate that 17β-estradiol interfers with the development of central sensitization and confirm that gender dimorphism should be considered when looking at pain evaluation.

• Authors: Sokhna Keita-Alassane, Colombe Otis, Emilie Bouet, Martin Guillot, Marilyn Frezier, Aliénor Delsart, Maxim Moreau, Agathe Bédard, Isabelle Gaumond, Jean-Pierre Pelletier, Johanne Martel-Pelletier, Francis Beaudry, Bertrand Lussier, Roger Lecomte, Serge Marchand, Eric Troncy
• Journal: Naunyn-Schmiedeberg's archives of pharmacology (Naunyn Schmiedebergs Arch Pharmacol) Vol. 395 Issue 6 Pg. 703-715 (06 2022) ISSN: 1432-1912 [Electronic] Germany
• PMID: 35318491 (Publication Type: Journal Article)
• Copyright: © 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Chemical References

• Calcitonin Gene-Related Peptide
• Estradiol
• Substance P

Topics

• Animals
• Female
• Rats
• Calcitonin Gene-Related Peptide (metabolism)
• Estradiol (pharmacology)
• Osteoarthritis (drug therapy)
• Pain (metabolism)
• Prospective Studies
• Rats, Sprague-Dawley
• Substance P (metabolism)