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J Pharm Pharmacol. 2016 Aug;68(8):1041-50. doi: 10.1111/jphp.12584. Epub 2016 Jun 12.

Antihyperalgesic effects of dexketoprofen and tramadol in a model of postoperative pain in mice - effects on glial cell activation.

Author information

1
Pain Research Unit, Department of Anesthesiology, IMIM-Institut Hospital del Mar d'Investigacions Biomèdiques, Universitat Autònoma de Barcelona School of Medicine, Barcelona, Spain.

Abstract

OBJECTIVES:

To define likely targets (i.e. glia) and protocols (analgesic combinations) to improve postoperative pain outcomes and reduce chronic pain after surgery. Specifically, to assess the antihyperalgesic effects of the dexketoprofen : tramadol (DEX : TRM) combination, exploring the implication of glial activation.

METHODS:

In a mouse model of postincisional pain, we evaluated mechanical nociceptive thresholds (Von Frey) for 21 days postoperatively. We assessed DEX and TRM alone and combined (1 : 1 ratio) on postoperative hyperalgesia (POH, day 1) and delayed latent pain sensitisation (substantiated by a naloxone challenge; PS, day 21). The interactions were analysed using isobolograms, and concomitant changes in spinal glial cell activation were measured.

KEY FINDINGS:

On day 1, DEX completely blocked POH, whereas TRM induced 32% inhibition. TRM, but not DEX, partially (47%) protected against PS, at 21 days. Co-administration of DEX : TRM (1 : 1 ratio) showed additivity for antihyperalgesia. Both drugs and their combination totally inhibited surgery-induced microglia activation on day 1, but had no effect on surgery-induced astrocyte activation (1 day) or re-activation after naloxone (21 days).

CONCLUSIONS:

The DEX : TRM combination could have clinical advantages: a complete prevention of POH after surgery, together with a substantial (48%) inhibition of the development of PS by TRM. Microglia, but not astrocyte activation, could play a relevant role in the development of postoperative pain hypersensitivity.

KEYWORDS:

dexketoprofen; glial cells; latent pain sensitisation; postoperative hyperalgesia; tramadol

PMID:
27291294
DOI:
10.1111/jphp.12584
[Indexed for MEDLINE]

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