Second messengers mediating high-molecular-weight hyaluronan-induced antihyperalgesia in rats with chemotherapy-induced peripheral neuropathy.
Second messengers mediating high-molecular-weight hyaluronan-induced antihyperalgesia in rats with chemotherapy-induced peripheral neuropathy.
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DOI：
10.1097/j.pain.0000000000002558
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发表时间：
2022-09-01
期刊：
影响因子：
7.4
通讯作者：
中科院分区：
文献类型：
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高分子量透明质酸（HMWH）是一种致敏剂，作用于伤害感受器上的同源透明质酸受体cd44，在炎症性和神经性疼痛的临床前模型中，它可以诱导抗痛觉过敏。在本实验中，我们研究了介导hmwhh诱导的与奥沙利铂和紫杉醇化疗诱导的周围神经病变（CIPN）相关的疼痛衰减的CD44第二信使。虽然HMWH仅在雄性大鼠中减弱CIPN，但在卵巢切除术或鞘内给药G蛋白偶联雌激素受体（GPR30） mRNA的寡脱氧核苷酸（ODN）反义后，雌性大鼠也对HMWH敏感。鞘内注射CD44 mRNA的ODN反义蛋白可显著减弱奥沙利铂或紫杉醇诱导的雄性CIPN大鼠hmwh诱导的抗痛症过敏。皮内给予CD44第二信使，RhoA （GTPases的Rho家族成员），磷脂酶C和磷脂酰肌醇（PI） 3-激酶γ (PI3Kg)的抑制剂，与鞘内给予ODN反义的PI3Kg一样，可以减轻hmwhh诱导的抗痛觉过敏。我们的研究结果表明，HMWH通过其对CD44的作用以及RhoA、磷脂酶C和PI3Kg的下游信号通路介导了CIPN的抗痛觉过敏。
High-molecular-weight hyaluronan (HMWH) is an agonist at cluster of differentiation (CD) 44, the cognate hyaluronan receptor, on nociceptors, where it acts to induce antihyperalgesia in preclinical models of inflammatory and neuropathic pain. In the present experiments, we studied the CD44 second messengers that mediate HMWH-induced attenuation of pain associated with oxaliplatin and paclitaxel chemotherapy-induced peripheral neuropathy (CIPN). While HMWH attenuated CIPN only in male rats, after ovariectomy or intrathecal administration of an oligodeoxynucleotide (ODN) antisense to G protein–coupled estrogen receptor (GPR30) mRNA, female rats were also sensitive to HMWH. Intrathecal administration of an ODN antisense to CD44 mRNA markedly attenuated HMWH-induced antihyperalgesia in male rats with CIPN induced by oxaliplatin or paclitaxel. Intradermal administration of inhibitors of CD44 second messengers, RhoA (member of the Rho family of GTPases), phospholipase C, and phosphatidylinositol (PI) 3-kinase gamma (PI3Kg), attenuated HMWH-induced antihyperalgesia as does intrathecal administration of an ODN antisense to PI3Kg. Our results demonstrated that HMWH induced antihyperalgesia in CIPN, mediated by its action at CD44 and downstream signaling by RhoA, phospholipase C, and PI3Kg.
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DOI：
10.1523/jneurosci.5138-11.2012
发表时间：
2012-02-08
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Bogen O;Alessandri-Haber N;Chu C;Gear RW;Levine JD
通讯作者：
Levine JD
影响因子：
7.4
作者：
Bonet IJM;Green PG;Levine JD
通讯作者：
Levine JD
影响因子：
5.3
作者：
Bonet, Ivan J. M.;Araldi, Dioneia;Levine, Jon D.
通讯作者：
Levine, Jon D.
影响因子：
7.3
作者：
Cejalvo, Juan-Miguel;Jacob, Wolfgang;Cervantes, Andres
通讯作者：
Cervantes, Andres
奥沙利铂诱发的神经病变：遗传和表观遗传特征，以更好地了解如何改善这种副作用。
影响因子：
5
作者：
Branca JJV;Carrino D;Gulisano M;Ghelardini C;Di Cesare Mannelli L;Pacini A
通讯作者：
Pacini A