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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Long-Term Antidepressant Treatment Inhibits Neuropathic Pain-Induced CREB and PLC gamma-1 Phosphorylation in the Mouse Spinal Cord Dorsal Horn

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Kusuda, Ricardo [1] ; Ravanelli, Maria I. [1] ; Cadetti, Flaviane [1, 2] ; Franciosi, Adriano [1] ; Previdelli, Karina [1, 2] ; Zanon, Sonia [1] ; Lucas, Guilherme [1]
Total Authors: 7
[1] Univ Sao Paulo, Pain Neurobiol Lab, Dept Physiol, Ribeirao Preto Sch Med, Sao Paulo - Brazil
[2] Univ Sao Paulo, Dept Neurosci & Behav, Div Neurol, Ribeirao Preto Sch Med, Sao Paulo - Brazil
Total Affiliations: 2
Document type: Journal article
Source: JOURNAL OF PAIN; v. 14, n. 10, p. 1162-1172, OCT 2013.
Web of Science Citations: 5

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 gamma-1 (PLC gamma-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 PLC gamma-1 but not extracellular signal-regulated kinase (ERK42), 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 PLCy-1 phosphorylation but had no effect on ERK1,2, p38, and c-Jun N-terminal kinase activity. These results indicate that long-term administration of imipramine 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 PLC gamma-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. (C) 2013 by the American Pain Society (AU)

FAPESP's process: 06/00479-0 - Neurotrophins action on the antinociceptive activity mediated by the monoaminergic system: integrating neurogenesis and neuropathic pain mechanisms
Grantee:Guilherme de Araújo Lucas
Support Opportunities: Regular Research Grants