Research Group in Animal Pharmacology of Quebec (GREPAQ), Department of Veterinary Biomedicine, Faculty of Veterinary Medicine, Université de Montréal, Saint Hyacinthe, QC, Canada.
Osteoarthritis Research Unit, University of Montreal Hospital Research Center (CRCHUM), Montreal, QC, Canada.
Naunyn Schmiedebergs Arch Pharmacol. 2022 Jun;395(6):703-715. doi: 10.1007/s00210-022-02231-5. Epub 2022 Mar 23.
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).
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).
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).
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.
几项观察性研究表明，雌激素可能会影响疼痛感知。为了评估雌激素浸渍对疼痛表达的影响，我们在手术诱导的骨关节炎（OA）的 Sprague-Dawley 大鼠模型中进行了一项前瞻性、随机、对照、盲法研究。
雌性大鼠接受卵巢切除术，并在 OVX 过程中皮下预先植入 17β-雌二醇（0.025mg，90 天释放时间）或安慰剂丸。35 天后，对 17β-雌二醇（OA-E）和安慰剂（OA-P）组进行手术诱导 OA。通过静态负重（SWB）和足底撤回阈值（PWT）测试评估机械性超敏反应。采用质谱法结合高效液相色谱-质谱法（HPLC-MS）定量测定脊髓促痛神经肽物质 P（SP）、降钙素基因相关肽（CGRP）、缓激肽（BK）、生长抑素（SST）和强啡肽-A（Dyn-A）。
与对照组相比，卵巢切除大鼠的 SP（P=0.009）和 CGRP（P=0.017）浓度更高。OA 诱导增加了 SP（+33%，P<0.020）和 BK（-20%，P<0.037）的脊髓水平。在功能评估时，OA-E 大鼠在第 7 天（P=0.027）和第 56 天（P=0.033）对受累后肢的体重百分比高于 OA-P 大鼠，并且在第 56 天的 PWT 更高（P=0.009），表明 17β-雌二醇具有镇痛和抗痛觉过敏作用。有趣的是，17β-雌二醇治疗可对抗脊髓 Dyn-A（P<0.016）和 CGRP（P<0.018）浓度的增加。
这些结果清楚地表明，17β-雌二醇干扰了中枢敏化的发展，并证实了在评估疼痛时应考虑性别二态性。
