Pre-injury Administration of Morphine Prevents Development of Neuropathic Hyperalgesia Through Activation of Descending Monoaminergic Mechanisms in the Spinal Cord in Mice

Overview

Journal Mol Pain

Date 2005 Jun 4

PMID 15932652

Citations 1

Authors

Md Harunor Rashid

Hiroshi Ueda

Affiliations

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Abstract

The present study examined whether pre-injury administration of morphine can prevent partial sciatic nerve injury-induced neuropathic pain in mice. We observed that pre-injury administration of subcutaneous (s.c.) and intracerebroventricular (i.c.v.) morphine dose-dependently prevented the development of both thermal and mechanical hyperalgesia at 7 days following nerve injury in mice. The pre-injury morphine (s.c.)-induced analgesia was significantly blocked by pretreatment with naloxone injected s.c. or i.c.v., but not i.t., suggesting that systemic morphine produced the pre-emptying effects mainly by acting at the supra-spinal sites. Since it is believed that activation of descending monoaminergic mechanisms in spinal cord largely contributes to the supra-spinal analgesic effects of morphine, we investigated the involvement of serotonergic and noradrenergic mechanisms in spinal cord in the pre-injury morphine-induced analgesic effects. We found that pre-injury s.c. morphine-induced analgesic effect was significantly blocked by i.t. pretreatment with serotonergic antagonist, methysergide and noradrenergic antagonist, phentolamine. In addition, pre-injury i.t. injection of serotonin uptake inhibitor, fluoxetine and alpha2-adrenergic agonist, clonidine significantly prevented the neuropathic hyperalgesia. We next examined whether pre-injury morphine prevented the expression of neuronal hyperactivity markers such as c-Fos and protein kinase C gamma (PKCgamma) in the spinal dorsal horn. We found that pre-injury administration of s.c. morphine prevented increased expressions of both c-Fos and PKCgamma observed following nerve injury. Similar results were obtained with i.t. fluoxetine and clonidine. Altogether these results suggest that pre-injury administration of morphine might prevent the development of neuropathic pain through activation of descending monoaminergic pain inhibitory pathways.

Citing Articles

Spinal neuronal activation during locomotor-like activity enabled by epidural stimulation and 5-hydroxytryptamine agonists in spinal rats.

Duru P, Tillakaratne N, Kim J, Zhong H, Stauber S, Pham T J Neurosci Res. 2015; 93(8):1229-39.

PMID: 25789848 PMC: 4478222. DOI: 10.1002/jnr.23579.

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