Increased capsaicin receptor TRPV1 in skin nerve fibres and related vanilloid receptors TRPV3 and TRPV4 in keratinocytes in human breast pain.
Increased capsaicin receptor TRPV1 in skin nerve fibres and related vanilloid receptors TRPV3 and TRPV4 in keratinocytes in human breast pain.
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DOI：
10.1186/1472-6874-5-2
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发表时间：
2005-03-08
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影响因子：
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通讯作者：
Anand, Praveen
中科院分区：
文献类型：
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作者：
Gopinath, Preethi;Wan, Elaine;Anand, Praveen
背景：乳房疼痛和压痛影响70%的妇女在某些时候。这些症状被归因于随着乳房尺寸的增加而拉伸神经，但组织机制尚不清楚。方法：招募了18名患者（n = 12例乳房缩小术和n = 6例乳房再造术），并通过临床问卷评估乳房疼痛。使用辣椒素受体TRPV 1、相关香草素热感受器TRPV 3和TRPV 4以及神经生长因子（NGF）的特异性抗体，对每位患者的乳腺皮肤活检进行检查。研究结果：TRPV 1阳性表皮内神经纤维在乳房疼痛和压痛患者中显著增加（TRPV 1纤维/ mm表皮，中位数[范围] -无疼痛组，n = 8，0.69 [0-1.27];疼痛组，n = 10，2.15 [0.77-4.38]; p = 0.0009）。神经生长因子，上调TRPV 1和诱导神经发芽，存在于基底角化细胞：一些乳房疼痛标本也显示在基底角化细胞上的NGF染色。TRPV 4免疫反应阳性纤维存在于表皮下，但在疼痛的乳腺组织中没有显着变化。TRPV 3和TRPV 4在乳房疼痛组织中的角质形成细胞中均显著增加; TRPV 3，中位数[范围] -无疼痛组，n = 6，0.75 [0-2];疼痛组，n = 11，2 123，p = 0.008; TRPV 4，中位数[范围] -无疼痛组，n = 6，[0-1];疼痛组，n = 11，1 [0.5-2]，p = 0.014）。结论：增加TRPV 1表皮内神经纤维可能代表侧枝芽，或神经牵拉和多模态伤害感受器损伤后的神经再支配。选择性TRPV 1阻断剂可能为乳房疼痛提供新的治疗方法。TRPV 3和TRPV 4在角质形成细胞中的作用值得进一步研究。
BACKGROUND: Breast pain and tenderness affects 70% of women at some time. These symptoms have been attributed to stretching of the nerves with increase in breast size, but tissue mechanisms are poorly understood. METHODS: Eighteen patients (n = 12 breast reduction and n = 6 breast reconstruction) were recruited and assessed for breast pain by clinical questionnaire. Breast skin biopsies from each patient were examined using immunohistological methods with specific antibodies to the capsaicin receptor TRPV1, related vanilloid thermoreceptors TRPV3 and TRPV4, and nerve growth factor (NGF). RESULTS: TRPV1-positive intra-epidermal nerve fibres were significantly increased in patients with breast pain and tenderness (TRPV1 fibres / mm epidermis, median [range] - no pain group, n = 8, 0.69 [0-1.27]; pain group, n = 10, 2.15 [0.77-4.38]; p = 0.0009). Nerve Growth Factor, which up-regulates TRPV1 and induces nerve sprouting, was present basal keratinocytes: some breast pain specimens also showed NGF staining in supra-basal keratinocytes. TRPV4-immunoreactive fibres were present in sub-epidermis but not significantly changed in painful breast tissue. Both TRPV3 and TRPV4 were significantly increased in keratinocytes in breast pain tissues; TRPV3, median [range] - no pain group, n = 6, 0.75 [0-2]; pain group, n = 11, 2 123, p = 0.008; TRPV4, median [range] - no pain group, n = 6, [0-1]; pain group, n = 11, 1 [0.5-2], p = 0.014). CONCLUSION: Increased TRPV1 intra-epidermal nerve fibres could represent collateral sprouts, or re-innervation following nerve stretch and damage by polymodal nociceptors. Selective TRPV1-blockers may provide new therapy in breast pain. The role of TRPV3 and TRPV4 changes in keratinocytes deserve further study.