Long-Term Antidepressant Treatment Inhibits Neuropathic Pain-Induced CREB and PLCγ-1 Phosphorylation in the Mouse Spinal Cord Dorsal Horn
| Autor: | Karina Previdelli, Ricardo Kusuda, Adriano Cardozo Franciosi, F. Cadetti, Maria Ida Bonini Ravanelli, Sonia Zanon, Guilherme de Araújo Lucas |
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| Rok vydání: | 2013 |
| Předmět: |
Male
Imipramine medicine.medical_specialty MAP Kinase Signaling System medicine.drug_class Blotting Western Tricyclic antidepressant Antidepressive Agents Tricyclic CREB p38 Mitogen-Activated Protein Kinases Mice Sciatica Internal medicine Spinal Cord Dorsal Horn Animals Medicine Phosphorylation Cyclic AMP Response Element-Binding Protein Pain Measurement Mice Inbred BALB C Behavior Animal biology Phospholipase C gamma business.industry ADENOSINA Nerve injury Immunohistochemistry Antidepressive Agents Posterior Horn Cells Anesthesiology and Pain Medicine Endocrinology Nociception Neurology Neuropathic pain Peripheral nerve injury biology.protein Neuralgia Neurology (clinical) Mitogen-Activated Protein Kinases medicine.symptom business medicine.drug |
| Zdroj: | Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP |
| ISSN: | 1526-5900 |
| Popis: | The effect of long-term administration of imipramine, a tricyclic antidepressant, on the phosphorylation status of cyclic adenosine monophosphate-responsive element-binding protein (CREB), mitogen-activated protein kinase family members, and phospholipase g-1 (PLCg-1) was investigated in the dorsal horn of the spinal cord following peripheral nerve lesion. Nerve injury induced an ipsilateral long-lasting increased phosphorylation of CREB and PLCg-1 but not extracellular signal-regulated kinase (ERK1,2), p38, and c-Jun N-terminal kinase. Daily administration of imipramine (5, 10, or 30 mg/kg) for 21 days progressively reduced both tactile-induced neuropathic pain hypersensitivity and thermal hyperalgesia. After withdrawal of treatment, the antinociceptive effect of imipramine was gradually abolished but still remained for at least 3 weeks. Conversely, no analgesic effect was observed with short-term imipramine treatment. Moreover, imipramine therapy reversed nerve injury-induced CREB and PLCg-1 phosphorylation but had no effect on ERK1,2, p38, andc-JunN-terminalkinaseactivity.Theseresultsindicatethatlong-termadministrationofimipramine may prevent some of the harmful changes in the spinal cord dorsal horn following nerve injury. However, imipramine analgesic effect takes time to develop and mature, which might explain in part why the clinical analgesic effect of tricyclic antidepressants develops with a delay after the beginning of treatment. Our data also provide evidence that prolonged imipramine treatment may induce antinociception in neuropathic pain conditions because of its action on the PLCg-1/CREB-signaling pathway. Perspective: This article demonstrates that long-term treatment with imipramine reverses some of the marked effects induced by peripheral nerve injury in the spinal dorsal horn that contribute to long-term maintenance of sensory disorder, providing a new view to the mechanisms of action of these drugs. |
| Databáze: | OpenAIRE |
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