Schmidt André P, Böhmer Ana Elisa, Schallenberger Cristhine, Antunes Catiele, Pereira Mery Stéfani L, Leke Renata, Wofchuk Susana T, Elisabetsky Elaine, Souza Diogo O
Graduate Program in Biochemistry, Department of Biochemistry, ICBS, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil.
Eur J Pharmacol. 2009 Jun 24;613(1-3):46-53. doi: 10.1016/j.ejphar.2009.04.018. Epub 2009 Apr 18.
It is well known that adenine-based purines exert multiple effects on pain transmission. Recently, we have demonstrated that intracerebroventricular (i.c.v.) administered guanine-based purines are antinociceptive against chemical and thermal pain models in mice. The present study was designed to further investigate the antinociceptive effects of guanosine in mice. Animals received an intrathecal (i.t.) injection of vehicle (0.1 mN NaOH) or guanosine (10 to 400 nmol). Measurements of cerebrospinal fluid (CSF) purine levels and spinal cord glutamate uptake were performed. Guanosine produced dose-dependent antinociceptive effects against tail-flick, hot-plate, intraplantar (i.pl.) capsaicin, and i.pl. glutamate tests. Additionally, i.t. guanosine produced significant inhibition of the biting behavior induced by i.t. injection of glutamate (175 nmol/site), AMPA (135 pmol/site), kainate (110 pmol/site), trans-ACPD (50 nmol/site), and substance P (135 ng/site), with mean ID(50) values of 140 (103-190), 136 (100-185), 162 (133-196), 266 (153-461) and 28 (3-292) nmol, respectively. However, guanosine failed to affect the nociception induced by NMDA (450 pmol/site) and capsaicin (30 ng/site). Intrathecal administration of guanosine (200 nmol) induced an approximately 120-fold increase on CSF guanosine levels. Guanosine prevented the increase on spinal cord glutamate uptake induced by i.pl. capsaicin. This study provides new evidence on the mechanism of action of guanosine presenting antinociceptive effects at spinal sites. This effect seems to be at least partially associated with modulation of glutamatergic pathways by guanosine.
众所周知，基于腺嘌呤的嘌呤对疼痛传递有多种影响。最近，我们已经证明，脑室内（i.c.v.）给予的基于鸟嘌呤的嘌呤对小鼠的化学性和热性疼痛模型具有镇痛作用。本研究旨在进一步探讨鸟苷在小鼠中的镇痛作用。动物接受鞘内（i.t.）注射溶剂（0.1 mN NaOH）或鸟苷（10至400 nmol）。进行了脑脊液（CSF）嘌呤水平和脊髓谷氨酸摄取的测量。鸟苷对甩尾、热板、足底内（i.pl.）辣椒素和i.pl.谷氨酸试验产生剂量依赖性镇痛作用。此外，i.t.鸟苷显著抑制了i.t.注射谷氨酸（175 nmol/部位）、AMPA（135 pmol/部位）、海人藻酸（110 pmol/部位）、反式-ACPD（50 nmol/部位）和P物质（135 ng/部位）诱导的咬行为，平均ID(50)值分别为140（103 - 190）、136（100 - 185）、162（133 - 196）、266（153 - 461）和28（3 - 292）nmol。然而，鸟苷未能影响NMDA（450 pmol/部位）和辣椒素（30 ng/部位）诱导的伤害感受。鞘内给予鸟苷（200 nmol）可使CSF鸟苷水平增加约120倍。鸟苷可防止i.pl.辣椒素诱导的脊髓谷氨酸摄取增加。本研究为鸟苷在脊髓部位呈现镇痛作用的作用机制提供了新证据。这种作用似乎至少部分与鸟苷对谷氨酸能通路的调节有关。
