Pretreatment with intrathecal amitriptyline potentiates anti-hyperalgesic effects of post-injury intra-peritoneal amitriptyline following spinal nerve ligationReport as inadecuate




Pretreatment with intrathecal amitriptyline potentiates anti-hyperalgesic effects of post-injury intra-peritoneal amitriptyline following spinal nerve ligation - Download this document for free, or read online. Document in PDF available to download.

BMC Neurology

, 12:44

Headache

Abstract

BackgroundAmitriptyline, a tricyclic antidepressant and potent use-dependent blocker of sodium channels, has been shown to attenuate acute and chronic pain in several preclinical modes. The purpose of this study was to investigate whether intrathecal pretreatment with amitriptyline combined with post-injury intra-peritoneal amitriptyline is more effective than post-injury treatment alone on L5 spinal nerve ligation SNL-induced neuropathic pain.

Methods96 adult male Sprague–Dawley rats were allocated into 4 groups: group S , Sham; group L , L5 spinal nerve L igation with vehicle treatment; group A , SNL and post-injury intra-peritoneal A bdominal amitriptyline twice daily × 3 days; group P , intrathecal P retreatment with amitriptyline, SNL and intra-peritoneal amitriptyline twice daily × 3 days. Responses to thermal and mechanical stimuli, as well as sodium channel expression in injured dorsal root ganglion DRG and activated glial cells in spinal dorsal horn SDH were measured pre-operatively and on post-operative day POD 4, 7, 14, 21 and 28.

ResultsSNL-evoked hyper-sensitivity responses to thermal and mechanical stimuli, up-regulated Nav1.3 and down-regulated Nav1.8 expression in DRG, and activated microglia and astrocytes in SDH. In group A, intra-peritoneal amitriptyline alone alleviated thermal hypersensitivity on POD7, reversed Nav1.8 and reduced activated microglia on POD14. In group P, intrathecal pretreatment with amitriptyline not only potentiated the effect of intra-peritoneal amitriptyline on thermal hypersensitivity and Nav1.8, but attenuated mechanical hypersensitivity on POD7 and reduced up-regulated Nav1.3 on POD14. Furthermore, this treatment regimen reduced astrocyte activation on POD14.

ConclusionsConcomitant intrathecal pretreatment and post-injury intra-peritoneal amitriptyline was more effective than post-injury treatment alone on attenuation of behavioral hypersensitivity, decrease of activated microglia and astrocytes and dysregulated Nav1.3 and 1.8.

KeywordsIntrathecal amitriptyline Allodynia Sodium channels Microglia Astrocyte Electronic supplementary materialThe online version of this article doi:10.1186-1471-2377-12-44 contains supplementary material, which is available to authorized users.

Chung-Sheng Lai and Aij-Lie Kwan contributed equally to this work.

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Author: Kuang-I Cheng - Hung-Chen Wang - Lin-Li Chang - Fu-Yen Wang - Chung-Sheng Lai - Chao-Wen Chou - Hung-Pei Tsai - Aij-Lie Kw

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