薬理と治療

Abstract

Orexins are initially known to be a hypothalamic peptide critical for feeding and normal wakefulness. In addition, orexins are also involved in the regulation of nociceptive processing, suggesting a novel potential therapeutic approach for pain treatment. Morphological results show that orexin A is distributed in DRG neurons. SNL of neuropathic pain has been widely used for various investigative works on neuropathic pain mechanisms. We have investigated the effects of lidocaine and orexinA on high K＋︱induced［Ca2＋］i increase in sham and segmental spinal nerve ligation（SNL）model rat dorsal root ganglion （DRG）neurons. Ten male Wistar rats were randomly assigned for one independent experiments（n＝5⊠2）：sham group, experimental group（SNL group）. DRG neurons were depolarized by exposure to 50 mM K＋ and the rise of ［Ca2＋］i was measured using fura︱2 as an indicator. Nifedipine and lidocaine strongly inhibited on the high K＋︱induced depolarization［Ca2＋］i increase in sham and SNL groups. OrexineA inhibited on the high K＋︱induced depolarization ［Ca2＋］i increase in SNL rat DRG neurons, but was little or no effect in sham group. Thus, the effect of orexinA on high K＋︱induced［Ca2＋］i increase was considered to be due to blocking Ca2＋ influx through L︱type Ca2＋ channel, which may have important implications for nociceptive modulation and pain.