Cooperative N
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- 作者：Maria Luisa Sotgiu ; Maurizio Valente ; Riccardo Storchi ; Giancarlo Caramenti ; Gabriele E.M. Biella
- 关键词：Methadone ; Opioid receptors ; NMDA receptors ; Rat spinal WDR neurons ; Neuropathic pain
- 刊名：Pharmacological Research
- 出版年：2009
- 出版时间：October 2009
- 年：2009
- 卷：60
- 期：4
- 页码：284-290
- 全文大小：487 K
文摘
Methadone (Racemic methadone) exerts its antinociceptive effect by activation of μ-opioid receptors and/or blockade of NMDA receptors. The aim of this study is to determine whether the methadone analgesic effect on neuropathic pain is achieved only by the agonism of the μ-opioid receptors or cooperatively with the antagonism of the NMDA receptors. To this purpose, in rats with neuropathic pain model of chronic constriction of one sciatic nerve (CCI rats), we administered methadone before or after opioid receptor blockade with naloxone and checked its effects on the spinal Wide Dynamic Range (WDR) neuron dynamics in three experimental conditions: on the spontaneous and noxious evoked neuronal activities in control rats (sham operated and naïve); on iontophoretic NMDA induced neuronal hyperactivity in intact rats; on pain-related spontaneous and noxious evoked hyperactivities in CCI rats. The results, as from the spike-frequency analysis, show that: (i) in control rats, methadone inhibits the noxious evoked neuronal activity and naloxone prevents or reverses about 94 % of methadone inhibitory effect; (ii) in intact rats, pretreated with naloxone, methadone reduces the NMDA induced neuronal hyperactivity; (iii) in CCI rats, methadone inhibits the neuronal spontaneous and noxious evoked hyperactivities, and naloxone prevents or reverses about 60 % of methadone inhibitory effect.
These findings allow to conclude that methadone inhibition of the noxious evoked activity in normal rats is achieved predominantly through the agonism of the μ-opioid receptors, while the inhibition of the pain-related hyperactivity in rats with signs of neuropathic pain (CCI rats), involves also the NMDA receptors antagonism.