Temporomandibular disorder (TMD) is commonly comorbid with fibromyalgia syndrome (FMS). The incidence of these pain conditions is prevalent in women and prone to mental stress. Chronic pain symptoms in patients with FMS and myofascial TMD (mTMD) are severe and debilitating. In the present study, we developed a new animal model to mimic the comorbidity of TMD and FMS. In ovariectomized female rats, repeated forced swim (FS) stress induced mechanical allodynia and thermal hyperalgesia in the hindpaws of the 17β-estradiol (E2) treated rats with orofacial inflammation. Subcutaneous injection of E2, injection of complete Freund’s adjuvant (CFA) into masseter muscles or FS alone did not induce somatic hyperalgesia. We also found that the somatic hyperalgesia was accompanied by upregulation of GluN1 receptor and serotonin (5-hydroxytryptamine, 5-HT)3A receptor expression in the dorsal horn of spinal cord at L4-L5 segments. Intrathecal injection of N-methyl-D-aspartic acid receptor (NMDAR) antagonist 2-amino-5-phosphonovaleric acid (APV) or 5-HT3 receptor antagonist Y-25130 blocked stress-induced wide-spreading hyperalgesia. These results suggest that NMDAR-dependent central sensitization in the spinal dorsal horn and 5-HT-dependent descending facilitation contribute to the development of wide-spreading hyperalgesia in this comorbid pain model.

中文翻译：

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中枢敏化对口面部炎症大鼠应激诱导的扩散性痛觉过敏的贡献。

颞下颌关节紊乱病 (TMD) 通常与纤维肌痛综合征 (FMS) 共病。这些疼痛状况的发生率在女性中很普遍，并且容易产生精神压力。FMS 和肌筋膜 TMD (mTMD) 患者的慢性疼痛症状严重且使人衰弱。在本研究中，我们开发了一种新的动物模型来模拟 TMD 和 FMS 的合并症。在切除卵巢的雌性大鼠中，反复强迫游泳 (FS) 应激会在 17β-雌二醇 (E2) 治疗的口面部炎症大鼠的后爪中引起机械性异常性疼痛和热痛觉过敏。皮下注射 E2、将完全弗氏佐剂 (CFA) 注射到咬肌或单独使用 FS 不会引起躯体痛觉过敏。我们还发现躯体痛觉过敏伴随着 GluN1 受体和 5-羟色胺（5-羟色胺，5-HT)3A 受体在 L4-L5 节段脊髓背角的表达。鞘内注射 N-甲基-D-天冬氨酸受体 (NMDAR) 拮抗剂 2-氨基-5-磷酸新戊酸 (APV) 或 5-HT3 受体拮抗剂 Y-25130 可阻断应激诱导的广泛传播的痛觉过敏。这些结果表明，脊髓背角的 NMDAR 依赖性中枢敏化和 5-HT 依赖性下行促进有助于在这种共病疼痛模型中发生广泛传播的痛觉过敏。