| Autor: |
Laurence Meyer, Christine Venard, Véronique Schaeffer, Christine Patte-Mensah, Ayikoe G. Mensah-Nyagan |
| Jazyk: |
angličtina |
| Rok vydání: |
2008 |
| Předmět: |
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| Zdroj: |
Neurobiology of Disease, Vol 30, Iss 1, Pp 30-41 (2008) |
| Druh dokumentu: |
article |
| ISSN: |
1095-953X |
| DOI: |
10.1016/j.nbd.2007.12.001 |
| Popis: |
Identification of cellular targets pertinent for the development of effective therapies against pathological pain constitutes a difficult challenge. We combined several approaches to show that 3α-hydroxysteroid oxido-reductase (3α-HSOR), abundantly expressed in the spinal cord (SC), is a key target, the modulation of which markedly affects nociception. 3α-HSOR catalyzes the biosynthesis and oxidation of 3α,5α-reduced neurosteroids as allopregnanolone (3α,5α-THP), which stimulates GABAA receptors. Intrathecal injection of Provera (pharmacological inhibitor of 3α-HSOR activity) in naive rat SC decreased thermal and mechanical nociceptive thresholds assessed with behavioral methods. In contrast, pain thresholds were dose-dependently increased by 3α,5α-THP. In animals subjected to sciatic nerve injury-evoked neuropathic pain, molecular and biochemical experiments revealed an up-regulation of 3α-HSOR reductive activity in the SC. Enhancement of 3α,5α-THP concentration in the SC induced analgesia in neuropathic rats while Provera exacerbated their pathological state. Possibilities are opened for chronic pain control with drugs modulating 3α-HSOR activity in nerve cells. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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