Prolactin modulates TRPV1 in female rat trigeminal sensory neurons
Prolactin modulates TRPV1 in female rat trigeminal sensory neurons
复制标题
DOI：
10.1523/jneurosci.0793-06.2006
复制
发表时间：
2006-08-02
影响因子：
5.3
通讯作者：
Hargreaves, Kenneth M.
中科院分区：
文献类型：
--
作者：
Diogenes, Anibal;Patwardhan, Amol M.;Hargreaves, Kenneth M.
疼痛感知的性别依赖性是有据可查的，被认为是由于生殖激素对伤害性处理的影响。在本研究中，我们评估雌二醇是否改变卵巢切除大鼠（OVX）三叉神经节（TG）的基因转录。这些实验表明，17-β-雌二醇（E2）使TG中的催乳素（PRL）表达急剧上调（40倍）。PRL表达仅限于TG神经元，与TG中的瞬时电位受体香草酸1型（TRPV 1）高度重叠（相似于90%）。此外，PRL在刺激期间从神经元释放。两种形式的PRL受体（PRLRs），短和长，也存在于TG神经元。此外，长PRLR的表达受雌二醇的控制。我们接下来评估了PRL作为感觉神经元的神经调质的新假设。PRL预处理显著增强辣椒素诱发的内向电流，钙内流，和免疫反应性降钙素基因相关肽从培养的TG神经元释放。这种PRL调制辣椒素的反应被取消的E2从TG文化撤出。生化分析表明，PRL增加（> 50%）TRPV 1的磷酸化水平在TG。在行为测试中，PRL预处理显着增强辣椒素诱发的伤害性行为，雌性大鼠在发情前期和OVX大鼠后E2治疗。PRL对辣椒素反应的体内增强作用也依赖于E2。总的来说，这些数据表明，PRL是一种新的调制器的感觉神经元密切调节E2。这些发现与PRL可能有助于某些疼痛疾病的发展的假设一致，可能包括那些由雌激素调节的疼痛疾病。
Sex dependency in pain perception is well documented and is thought to be attributable to the effect of reproductive hormones on nociceptive processing. In the present study, we evaluated whether estradiol alters gene transcription in the trigeminal ganglia (TG) of ovariectomized rats (OVX). These experiments demonstrated a dramatic (40-fold) upregulation of prolactin (PRL) expression in TG by 17-beta-estradiol (E2). PRL expression was restricted to TG neurons and was highly overlapped with transient potential receptor vanilloid type 1 (TRPV1) ( similar to 90%) in TG. Additionally, PRL is released from neurons during stimulation. Both forms of PRL receptors (PRLRs), short and long, were also present in TG neurons. Moreover, expression of the long PRLRs was under control of estradiol. We next evaluated the novel hypothesis that PRL acts as a neuromodulator of sensory neurons. PRL pretreatment significantly enhanced capsaicin-evoked inward currents, calcium influx, and immunoreactive calcitonin gene-related peptide release from cultured TG neurons. This PRL modulation of capsaicin responses was abolished by withdrawal of E2 from TG cultures. Biochemical analysis demonstrated that PRL increased ( > 50%) phosphorylation levels of TRPV1 in TG. In a behavioral test, PRL pretreatment significantly potentiated capsaicin-evoked nocifensive behavior in female rats at proestrous and in OVX rats after E2 treatment. The in vivo potentiating effect of PRL on capsaicin responses was also dependent on E2. Collectively, these data demonstrate that PRL is a novel modulator of sensory neurons tightly regulated by E2. These findings are consistent with the hypothesis that PRL could contribute to the development of certain pain disorders, possibly including those modulated by estrogen.