Nojima Hiroshi, Simons Christopher T, Cuellar Jason M, Carstens Mirela Iodi, Moore Justin A, Carstens Earl
Department of Applied Pharmacology, Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, Toyama 930-0194, Japan.
J Neurosci. 2003 Nov 26;23(34):10784-90. doi: 10.1523/JNEUROSCI.23-34-10784.2003.
We investigated a spinal site for opioid modulation of itch-related scratching behavior in rats. Intradermal 5-HT (2%, 10 microl) elicited intermittent bouts of hindlimb scratching directed toward the injection site (nape of neck) beginning within minutes and lasting >1 hr. 5-HT-evoked scratching was significantly reduced by systemic administration of the opiate antagonist naltrexone but was not affected by systemic morphine at a dosage (3 mg/kg) that induces analgesia. Intradermal 5-HT elicited a significant increase in c-fos-like immunoreactivity (FLI) in superficial laminas I-III at the lateral aspect of the cervical C3-C6 dorsal horn compared with controls receiving intradermal saline. Neither systemic morphine nor naltrexone significantly affected counts of 5-HT-evoked FLI. The lack of effect of morphine suggests that intradermal 5-HT activates dorsal horn neurons, signaling itch but not pain. Attenuation of 5-HT-evoked scratching but not spinal FLI by naltrexone suggests a supraspinal site for its antipruritic action. In contrast, morphine significantly attenuated FLI elicited by intradermal capsaicin, a chemical that induces pain but not scratching.
我们研究了大鼠中阿片类物质对瘙痒相关抓挠行为进行调节的脊髓位点。皮内注射5-羟色胺(5-HT,2%,10微升)在数分钟内引发间歇性后肢抓挠,抓挠方向朝向注射部位(颈部),并持续超过1小时。全身性给予阿片类拮抗剂纳曲酮可显著减少5-HT诱发的抓挠,但在诱导镇痛的剂量(3毫克/千克)下,全身性给予吗啡对其没有影响。与接受皮内注射生理盐水的对照组相比,皮内注射5-HT可使颈髓C3-C6背角外侧I-III浅层的c-fos样免疫反应性(FLI)显著增加。全身性给予吗啡或纳曲酮均未显著影响5-HT诱发的FLI计数。吗啡无作用表明皮内注射5-HT激活了背角神经元,传递瘙痒而非疼痛信号。纳曲酮可减弱5-HT诱发的抓挠,但不影响脊髓FLI,这表明其止痒作用位点在脊髓以上。相比之下,吗啡可显著减弱皮内注射辣椒素诱发的FLI,辣椒素是一种诱发疼痛但不诱发抓挠的化学物质。