Antihyperalgesic effects of dexketoprofen and tramadol in a model of postoperative pain in mice - effects on glial cell activation
| Autor: | Elizabeth Romero-Alejo, Asunción Blanco Romero, Margarita M. Puig |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Male Pain Threshold Analgesic Pharmaceutical Science (+)-Naloxone Pharmacology 03 medical and health sciences Mice 0302 clinical medicine Threshold of pain medicine Animals Tramadol Analgesics Pain Postoperative business.industry Naloxone Anti-Inflammatory Agents Non-Steroidal Chronic pain medicine.disease Dexketoprofen Analgesics Opioid Disease Models Animal Drug Combinations 030104 developmental biology Nociception Hyperalgesia Ketoprofen Anesthesia medicine.symptom Cell activation business Neuroglia 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | The Journal of pharmacy and pharmacology. 68(8) |
| ISSN: | 2042-7158 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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