Estrogenic impregnation alters pain expression: analysis through functional neuropeptidomics in a surgical rat model of osteoarthritis
- PMID: 35318491
- DOI: 10.1007/s00210-022-02231-5
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.
Keywords: 17β-estradiol; Animal model; Cartilage; Neuropeptide; Osteoarthritis.
© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
Similar articles
-
Spinal neuropeptide modulation, functional assessment and cartilage lesions in a monosodium iodoacetate rat model of osteoarthritis.Neuropeptides. 2017 Oct;65:56-62. doi: 10.1016/j.npep.2017.04.009. Epub 2017 Apr 24. Neuropeptides. 2017. PMID: 28456437
-
Osteoarthritic pain model influences functional outcomes and spinal neuropeptidomics: A pilot study in female rats.Can J Vet Res. 2019 Apr;83(2):133-141. Can J Vet Res. 2019. PMID: 31097875 Free PMC article.
-
A-995662 [(R)-8-(4-methyl-5-(4-(trifluoromethyl)phenyl)oxazol-2-ylamino)-1,2,3,4-tetrahydronaphthalen-2-ol], a novel, selective TRPV1 receptor antagonist, reduces spinal release of glutamate and CGRP in a rat knee joint pain model.Pain. 2010 Aug;150(2):319-326. doi: 10.1016/j.pain.2010.05.015. Epub 2010 Jun 19. Pain. 2010. PMID: 20621685
-
Immunohistochemical analysis of the effects of estrogen on intraarticular neurogenic inflammation in a rat anterior cruciate ligament transection model of osteoarthritis.Connect Tissue Res. 2012;53(3):197-206. doi: 10.3109/03008207.2011.628059. Epub 2011 Dec 5. Connect Tissue Res. 2012. PMID: 22141435
-
Sensitivity of functional targeted neuropeptide evaluation in testing pregabalin analgesic efficacy in a rat model of osteoarthritis pain.Clin Exp Pharmacol Physiol. 2019 Aug;46(8):723-733. doi: 10.1111/1440-1681.13100. Epub 2019 May 23. Clin Exp Pharmacol Physiol. 2019. PMID: 31046168
Cited by
-
Face and Predictive Validity of MI-RAT (Montreal Induction of Rat Arthritis Testing), a Surgical Model of Osteoarthritis Pain in Rodents Combined with Calibrated Exercise.Int J Mol Sci. 2023 Nov 15;24(22):16341. doi: 10.3390/ijms242216341. Int J Mol Sci. 2023. PMID: 38003530 Free PMC article.
-
Immunohistochemical expression of estrogen receptor alpha in the maxillary sinus, pulp, and periodontal ligament of adjacent teeth in late pregnancy in rats.Odontology. 2023 Jul;111(3):608-617. doi: 10.1007/s10266-022-00770-0. Epub 2022 Nov 25. Odontology. 2023. PMID: 36434465 Free PMC article.
References
-
- Amandusson A, Blomqvist A (2001) Estrogen receptors can regulate pain sensitivity. Possible explanation of certain chronic pain conditions. Lakartidningen 98:1774–1778 - PubMed
-
- Averbeck B, Rudolphi K, Michaelis M (2004) Osteoarthritic mice exhibit enhanced prostaglandin E2 and unchanged calcitonin gene-related peptide release in a novel isolated knee joint model. J Rheumatol 31:2013–2020 - PubMed
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Medical
Research Materials