Pancreatic cancer is one of the most aggressive and deadly malignancies with a very poor prognosis. Pancreatic cancer-induced visceral pain is very common and is generally presented among the initial symptoms in patients; such pain is strongly associated with poor quality of life, impaired functional activity, and decreased survival. However, the principal neurobiological mechanisms of pain caused by pancreatic cancer have not been fully elucidated. Accumulating studies have shown that miRNAs play a major role in chronic pain by suppressing key molecules involved in nociception. In the present study, we report that microRNA (miR)-330 is highly expressed in the spinal dorsal horn (SDH) of nude mice with pancreatic cancer pain. Mimicking pancreatic carcinoma-induced SDH miR-330 upregulation by microinjection of miR-330 mimic into the SDH significantly induced abdominal mechanical allodynia in normal nude mice. Additionally, we found that the expression of GABA_BR2 was significantly decreased in the SDH of nude mice with pancreatic cancer pain and was regulated directly by miR-330 both in vitro and in vivo. Furthermore, inhibition of miR-330 rescued the expression of GABA_BR2 and alleviated pancreatic carcinoma-induced abdominal pain hypersensitivity in nude mice with pancreatic carcinoma. These results show that miR-330 participates in the genesis of pancreatic carcinoma-induced pain hypersensitivity by inhibiting GABA_BR2 expression in the SDH and might be a potential therapeutic target for pancreatic cancer pain.

胰腺癌是最具侵袭性和致命性的恶性肿瘤之一，预后极差。胰腺癌引起的内脏痛很常见，一般出现在患者的首发症状中；这种疼痛与生活质量差、功能活动受损和存活率下降密切相关。然而，胰腺癌引起疼痛的主要神经生物学机制尚未完全阐明。越来越多的研究表明，miRNAs 通过抑制参与伤害感受的关键分子在慢性疼痛中发挥重要作用。在本研究中，我们报告了 microRNA (miR)-330 在胰腺癌痛裸鼠的脊髓背角 (SDH) 中高表达。通过将 miR-330 模拟物显微注射到 SDH 中模拟胰腺癌诱导的 SDH miR-330 上调，显着诱导了正常裸鼠的腹部机械性异常性疼痛。此外，我们发现 GABA 的表达_B R2 在患有胰腺癌痛的裸鼠的 SDH 中显着降低，并且在体外和体内均受 miR-330 直接调节。此外，抑制 miR-330 可以挽救 GABA _B R2的表达，并减轻胰腺癌裸鼠中胰腺癌引起的腹痛超敏反应。这些结果表明 miR-330 通过抑制SDH 中GABA _B R2 的表达参与胰腺癌诱导的疼痛超敏反应的发生，并且可能是胰腺癌疼痛的潜在治疗靶点。