Continuous Intrathecal Infusion of Cannabinoid Receptor Agonists Attenuates Nerve Ligation-Induced Pain in Rats

Sheng Jie Shiue, Hsien Yu Peng, Chung Ren Lin, Shih Wei Wang, Ruey Horng Rau, Jen Kun Cheng

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

Abstract

Background and Objectives: Cannabinoid receptors (CB1R/CB2R) are known to play important roles in pain transmission. In this study, we investigated the effects of continuous intrathecal infusion of CB1/2R agonists in the L5/6 spinal nerve ligation pain model. Methods: Under isoflurane anesthesia, rats received nerve ligation and intrathecal catheter connected to an infusion pump. After surgery, saline (1 μL/h), CB1/2R agonist WIN55,212-2, CB1R agonist ACEA, or CB2R agonist AM1241 (1 μmol/h) was given intrathecally for 7 days. The mechanical and thermal sensitivities of rat hindpaw were determined by von Frey hair and radiant heat tests. The expression of CB1/2R and protein levels of CB1/2R, Iba1, glial fibrillary acidic protein, and tumor necrosis factor α were examined by immunofluorescence study and Western blotting. Results: On postligation day 7, rats that received WIN55,212-2, ACEA or AM1241 had significantly higher mean withdrawal thresholds (6.8, 8.4, and 10.2 g) and latencies (6.3, 7.3, and 9.1 seconds) than did saline-treated rats (1.7 g, 2.2 seconds). Cannabinoid receptors were expressed not only in IB4+ (isolectin B4) and CGRP+ (calcitonin gene-related peptide) dorsal root ganglion neurons, their central terminals, and peripheral axons, but also in neurons, microglia, and astrocytes in spinal cord. Cannabinoid receptor agonists enhanced nerve ligation-induced up-regulation of cannabinoid receptor in spinal cord and dorsal root ganglion. Treatment with WIN55,212-2 or AM1241, but not ACEA, markedly reduced nerve ligation-induced up-regulation of Iba1, glial fibrillary acidic protein, and tumor necrosis factor α in spinal cord. Conclusions: Continuous intrathecal infusion of CB1/2R agonists elicits antinociception in the pain model. The mechanisms might involve their actions on neurons and glial cells. CB2R, but not CB1R, seems to play an important role in the regulation of nerve injury-induced neuroinflammation.

Original languageEnglish
Pages (from-to)499-506
Number of pages8
JournalRegional anesthesia and pain medicine
Volume42
Issue number4
DOIs
Publication statusPublished - 2017 Jul 1

All Science Journal Classification (ASJC) codes

  • Anesthesiology and Pain Medicine

Fingerprint Dive into the research topics of 'Continuous Intrathecal Infusion of Cannabinoid Receptor Agonists Attenuates Nerve Ligation-Induced Pain in Rats'. Together they form a unique fingerprint.

Cite this