Tympanidis Penelope, Casula Maria Anna, Yiangou Yiangos, Terenghi Giorgio, Dowd Pauline, Anand Praveen
Department of Dermatology, University College London Hospitals Trust, UK.
Eur J Pain. 2004 Apr;8(2):129-33. doi: 10.1016/S1090-3801(03)00085-5.
Vulvodynia is characterised by painful burning sensation, allodynia and hyperalgesia in the region of the vulval vestibulus. While in many patients the cause of vulvodynia remains uncertain, we and others have previously shown increased intraepithelial and papillary innervation in vulvodynia. The vanilloid receptor VR1 (TRPV1) is expressed by nociceptors, and is triggered by capsaicin, noxious heat, protons, and chemicals produced during inflammation. In the present study we show increased papillary VR1 fibres by immunostaining and image analysis in vulvodynia tissues compared to controls (p<0.002). VR1 expression was found to be significantly increased when the percentage area immunostained was expressed as a ratio of VR1 to PGP 9.5, a pan-neuronal marker (P=0.01). VR1-positive fine epidermal fibres also appeared to be increased in vulvodynia tissues, by inspection. Fibres immunoreactive to the voltage-gated sodium channel SNS1/PN3 (Nav1.8), also expressed by nociceptors, were relatively scarce in both vulvodynia and control tissues. We hypothesize that increased expression of VR1 by nociceptors could mediate some of the symptoms in vulvodynia, for which systemic or topical specific VR1 antagonists may provide novel treatment.
外阴痛的特征是外阴前庭区域出现灼痛、痛觉过敏和痛觉超敏。虽然在许多患者中,外阴痛的病因仍不明确,但我们和其他人之前已经表明,外阴痛患者的上皮内和乳头内神经支配增加。香草酸受体VR1(TRPV1)由伤害感受器表达,并由辣椒素、有害热、质子和炎症过程中产生的化学物质触发。在本研究中,我们通过免疫染色和图像分析发现,与对照组相比,外阴痛组织中的乳头VR1纤维增加(p<0.002)。当将免疫染色的百分比面积表示为VR1与泛神经元标志物PGP 9.5的比值时,发现VR1表达显著增加(P=0.01)。通过观察还发现,外阴痛组织中VR1阳性的细小表皮纤维似乎也增加了。对电压门控钠通道SNS1/PN3(Nav1.8)免疫反应的纤维,同样由伤害感受器表达,在外阴痛组织和对照组织中都相对较少。我们推测,伤害感受器VR1表达的增加可能介导了外阴痛的一些症状,对此全身性或局部性特异性VR1拮抗剂可能提供新的治疗方法。