Spinal dopaminergic D1-and D2-like receptors have a sex-dependent effect in an experimental model of fibromyalgia*

被引:5
作者
De la Luz-Cuellar, Yarim Elideth [1 ]
Coffeen, Ulises [2 ]
Mercado, Francisco [3 ]
Granados-Soto, Vinicio [1 ,4 ]
机构
[1] Cinvestav, Dept Farmacobiol, Neurobiol Pain Lab, South Campus, Mexico City, Mexico
[2] Inst Nacl Psiquiatria Ramon de la Fuente Muniz, Lab Neurofisiol Integrat, Direcc Invest Neurocienciasncias, Mexico City, Mexico
[3] Inst Nacl Psiquiatria Ramon de la Fuente Muniz, Lab Fisiol Celular, Direcc Invest Neurocienciasncias, Mexico City, Mexico
[4] Cinvestav, Dept Farmacobiol, Neurobiol Pain Lab, South Campus,Calz Tenorios 235, Mexico City 14330, Mexico
关键词
Dopamine D 1-like receptors; Dopamine D 2-like receptors; Fibromyalgia; Pain; Reserpine; SOCIAL INTERACTIONS; ESTROUS-CYCLE; PAIN; ESTRADIOL; ANTAGONISTS; EXPRESSION; NEURONS; PROGESTERONE; HYPERALGESIA; NOCICEPTION;
D O I
10.1016/j.ejphar.2023.175696
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
There is evidence about the importance of sex in pain. The purpose of this study was to investigate the effect of sex in the antiallodynic activity of spinal dopamine D1-and D2-like receptors in a model of fibromyalgia-type pain in rats. Reserpine induced the same extent of tactile allodynia in female and male rats. Intrathecal injection of SCH-23390 (3-30 nmol, D1-like receptor antagonist), pramipexole (0.15-15 nmol) or quinpirole (1-10 nmol D2- like receptor agonists) increased withdrawal threshold in reserpine-treated female rats. Those drugs induced a greater antiallodynic effect in female rats. Sex-difference was also observed in a nerve injury model. Ovariectomy abated the antiallodynic effect of SCH-23390 (30 nmol) in reserpine-treated rats, while systemic reconstitution of 178-estradiol levels or intrathecal injection of estrogen receptor-alpha agonist protopanaxatriol in ovariectomized reserpine-treated females restored the antiallodynic effect of SCH-23390. Intrathecal administration of ICI-182,780 (estrogen receptor-alpha/8 antagonist) or methyl-piperidino-pyrazole hydrate (estrogen receptor-alpha antag-onist) abated 178-estradiol-restored antiallodynic effect of SCH-23390 in rats. In contrast, ovariectomy slightly reduced the effect of pramipexole (15 nmol) or quinpirole (10 nmol) in reserpine-treated rats, whereas systemic reconstitution of 178-estradiol levels did not modify the antiallodynic effect of both drugs. Combination 178-estradiol/progesterone, but not 178-estradiol nor progesterone alone, restored the antiallodynic effect of pra-mipexole and quinpirole in the rats. Mifepristone (progesterone receptor antagonist) abated 178-estradiol + progesterone restoration of the antiallodynic effect of pramipexole and quinpirole. These data suggest that the antiallodynic effect of dopamine D1-and D2-like receptors in fibromyalgia-type pain depends on spinal 178-estradiol/estrogen receptor-alpha and progesterone receptors, respectively.
引用
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页数:10
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