Sexual dimorphism in the nociceptive effects of hyaluronan.
Sexual dimorphism in the nociceptive effects of hyaluronan.
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DOI：
10.1097/j.pain.0000000000002116
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发表时间：
2021-04-01
期刊：
影响因子：
7.4
通讯作者：
Levine JD
中科院分区：
文献类型：
--
作者：
Bonet IJM;Green PG;Levine JD
在后爪皮内给予低分子量透明质酸（LMWH）可诱导剂量依赖性（0.1、1或10 μg）机械性痛觉过敏，雄性和雌性大鼠的程度相似。然而，雌性动物的LMWH痛觉过敏持续时间更长。双侧卵巢切除术，并通过鞘内给药的寡脱氧核苷酸（ODN）反义G-蛋白偶联雌激素受体（GPR 30）mRNA，在女性中，表明雌激素依赖性消除这种性别二态性。为了评估LMWH诱导痛觉过敏的受体，将LMWH给予已经用与三种透明质酸受体之一的mRNA反义（或错配）的ODN预处理的雄性和雌性大鼠组，所述透明质酸受体是分化簇44（CD 44）、Toll样受体4（TLR 4）或HA介导的运动性受体（RHAMM）。而LMWH诱导的痛觉过敏的减弱在男性和女性的ODN预处理的CD 44和TLR 4 mRNA的反义，RHAMM反义预处理只减弱LMWH诱导的痛觉过敏的男性。然而，反义RHAMM的ODN在用反义GPR 30的ODN处理的雌性大鼠中以及在卵巢切除的雌性中减弱了LMWH诱导的痛觉过敏。高分子量透明质酸（HMWH）预处理可显著减弱雄性大鼠LMWH诱导的痛觉过敏，但对雌性大鼠无明显影响。在雌性动物中，性腺切除术或GPR 30表达反义ODN治疗后，HMWH对LMWH诱导的痛觉过敏的衰减与雄性动物相似。这些实验鉴定了LMWH产生机械性痛觉过敏的伤害感受器，在雌性大鼠中建立了RHAMM作用的雌激素依赖性，并建立了HMWH抑制LMWH诱导的痛觉过敏的雌激素依赖性。
Intradermal administration of low molecular weight hyaluronan (LMWH) in the hindpaw induced dose-dependent (0.1, 1, or 10 μg) mechanical hyperalgesia, of similar magnitude in male and female rats. However, the duration of LMWH hyperalgesia was greater in females. This sexual dimorphism was eliminated by bilateral ovariectomy, and by intrathecal administration of an oligodeoxynucleotide (ODN) antisense to the G-protein-coupled estrogen receptor (GPR30) mRNA, in females, indicating estrogen dependence. To assess the receptors at which LMWH acts to induce hyperalgesia, LMWH was administered to groups of male and female rats that had been pretreated with ODN antisense (or mismatch) to the mRNA for one of three hyaluronan receptors, cluster of differentiation 44 (CD44), toll-like receptor 4 (TLR4) or receptor for HA-mediated motility (RHAMM). While LMWH-induced hyperalgesia was attenuated in both male and female rats pretreated with ODN antisense for CD44 and TLR4 mRNA, RHAMM antisense pretreatment only attenuated LMWH-induced hyperalgesia in males. ODN antisense for RHAMM, however, attenuated LMWH-induced hyperalgesia in female rats treated with ODN antisense to GPR30, as well as in ovariectomized females. LMWH-induced hyperalgesia was significantly attenuated by pretreatment with high molecular weight hyaluronan (HMWH) in male, but not in female rats. Following gonadectomy or treatment with ODN antisense to GPR30 expression in females, HMWH produced similar attenuation of LMWH-induced hyperalgesia to that seen in males. These experiments identify nociceptors at which LMWH acts to produce mechanical hyperalgesia, establishes estrogen dependence in the role of RHAMM in female rats, and establishes estrogen-dependence in the inhibition of LMWH-induced hyperalgesia by HMWH.
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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：
3.3
作者：
Ferrari LF;Araldi D;Bogen O;Levine JD
通讯作者：
Levine JD
影响因子：
2.7
作者：
Bennett, HL;Gustafsson, JÅ;Keast, JR
通讯作者：
Keast, JR
影响因子：
4
作者：
Ferrari, Luiz F.;Levine, Jon D.
通讯作者：
Levine, Jon D.
影响因子：
4.6
作者：
Ferrari, Luiz F.;Khomula, Eugen V.;Levine, Jon D.
通讯作者：
Levine, Jon D.