Enhanced thermal antinociceptive potency and anti-allodynic effects of morphine following spinal administration of endotoxin

Catherine M Cahill,Andy Dray,Terence J Coderre

doi:10.1016/s0006-8993(02)03885-4

Abstract

Recently, an animal model of central inflammation characterized by widespread cutaneous hyperalgesia and allodynia following intracerebroventricular (i.c.v.) administration of lipopolysaccharide (LPS) was described. In the present study, we demonstrate that central administration of LPS via intrathecal (i.t.) injection produces bilateral tactile allodynia and thermal hyperalgesia in the rat. Also, the effects of morphine-induced antinociception were determined in this model. Here we demonstrate enhanced thermal antinociceptive potency of i.t. morphine in LPS-treated rats compared to controls. Intrathecal morphine was also effective in alleviating the tactile allodynia induced by LPS. Both the antinociceptive and anti-allodynic effects produced by i.t. morphine were completely antagonized by pretreatment with subcutaneous naloxone (1 mg kg −1). This study demonstrates the presence of both heat hyperalgesia and mechanical allodynia following central administration of LPS, and an increased antinociceptive potency of i.t. morphine in this model.

Highlights

Prolonged tissue damage or nerve injury often leads to chronic pain characterized by the genesis of hyperalgesia and / or allodynia, which persists after healing
It is well established that peripheral administration of lipopolysaccharide (LPS; endotoxin) interacts with various cell types to release cytokines IL-1, IL-6, and TNFa in the periphery and central nervous system, which can in turn precipitate hyperalgesia [51,52,53,54]
We demonstrate the incidence of thermal hyperalgesia and tactile allodynia following spinal administration of endotoxin

Summary

Introduction

Prolonged tissue damage or nerve injury often leads to chronic pain characterized by the genesis of hyperalgesia and / or allodynia, which persists after healing. Many animal models have been developed in an attempt to understand the etiologies of various pain syndromes following an inflammatory insult. These models include application of various chemical irritants to induce peripheral inflammation (complete Freund’s adjuvant, carrageenan, mustard oil and formalin), all of which elicit spontaneous pain and / or thermal hyperalgesia and tactile allodynia [15]. It is well established that peripheral administration of lipopolysaccharide (LPS; endotoxin) interacts with various cell types to release cytokines IL-1, IL-6, and TNFa in the periphery and central nervous system, which can in turn precipitate hyperalgesia [51,52,53,54]. Spinal administration of LPS produced an increase in the concentration of TNFa in the cerebrospinal fluid [48] as well as precipi-

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Conclusion