Anjaneyulu Muragundla, Chopra Kanwaljit
Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh-160014, India.
Eur J Pharmacol. 2006 May 24;538(1-3):80-4. doi: 10.1016/j.ejphar.2006.03.067. Epub 2006 Apr 4.
Clinical and experimental studies have been reported that antidepressant drugs can be used as co-analgesics in the management of neuropathic pain. However, the mechanism through which they alleviate pain still remains unclear. The aim of the present study was to investigate the possible mechanism of action of fluoxetine-induced antinociceptive effect in streptozotocin-induced diabetic mice, especially the involvement of non-serotonergic neurotransmitters and their receptors. Diabetes was induced in male Laka mice with a single intraperitoneal injection of streptozotocin (200 mg/kg). Four weeks after streptozotocin, diabetic mice were tested for pain responses in the tail-immersion and hot-plate assays. Diabetic mice exhibited significant hyperalgesia as compared with control mice. Fluoxetine (10 and 20 mg/kg, i.p) injected into diabetic mice produced an antinociceptive effect in both tail-immersion and hot-plate assays. The antinociceptive effect of fluoxetine in diabetic mice was significantly lower as compared with that in control mice. Pretreatment with a muscarinic receptor antagonist, atropine (2 and 5 mg/kg, i.p) and an opioid receptor antagonist, naloxone (2 and 5 mg/kg, i.p), but not the alpha(2)-adrenoreceptor antagonist, yohimbine (2 and 5 mg/kg, i.p) reversed the antinociceptive effect of fluoxetine (20 mg/kg). These results suggest that apart from serotonin pathway, muscarinic and opioid receptors also participate in fluoxetine-induced antinociception in diabetic neuropathic pain.
已有临床和实验研究报道，抗抑郁药物可作为辅助镇痛药用于治疗神经性疼痛。然而，其缓解疼痛的机制仍不清楚。本研究的目的是探讨氟西汀在链脲佐菌素诱导的糖尿病小鼠中产生抗伤害感受作用的可能机制，尤其是非血清素能神经递质及其受体的参与情况。通过单次腹腔注射链脲佐菌素（200 mg/kg）诱导雄性拉卡小鼠患糖尿病。链脲佐菌素注射四周后，对糖尿病小鼠进行尾浸法和热板试验以检测疼痛反应。与对照小鼠相比，糖尿病小鼠表现出明显的痛觉过敏。给糖尿病小鼠腹腔注射氟西汀（10和20 mg/kg）在尾浸法和热板试验中均产生了抗伤害感受作用。氟西汀对糖尿病小鼠的抗伤害感受作用与对照小鼠相比明显较低。用毒蕈碱受体拮抗剂阿托品（2和5 mg/kg，腹腔注射）和阿片受体拮抗剂纳洛酮（2和5 mg/kg，腹腔注射）预处理，但α2肾上腺素能受体拮抗剂育亨宾（2和5 mg/kg，腹腔注射）不能逆转氟西汀（20 mg/kg）的抗伤害感受作用。这些结果表明，除血清素途径外，毒蕈碱和阿片受体也参与了氟西汀在糖尿病性神经病变疼痛中诱导的抗伤害感受作用。
