| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 6262941 | Brain Research | 2015 | 9 Pages |
â¢Intrathecal 5-HT or 5-CT reversed tactile allodynia.â¢Methiothepin diminished 5-HT- or 5-CT-induced antiallodynia.â¢SB-699551 reduced 5-HT- or 5-CT-induced antiallodynia.â¢WAY-100635 or GR-127935 reduced 5-HT- or 5-CT-induced antiallodynia.â¢5-HT5A receptors are expressed in the dorsal spinal cord and DRG.
Serotonin (5-HT) participates in pain modulation by interacting with different 5-HT receptors. The role of 5-HT5A receptor in neuropathic pain has not previously studied. The purpose of this study was to investigate: A) the role of 5-HT5A receptors in rats subjected to spinal nerve injury; B) the expression of 5-HT5A receptors in dorsal spinal cord and dorsal root ganglia (DRG). Neuropathic pain was induced by L5/L6 spinal nerve ligation. Tactile allodynia in neuropathic rats was assessed with von Frey filaments. Western blot methodology was used to determine 5-HT5A receptor protein expression. Intrathecal administration (on day 14th) of 5-HT (10-100Â nmol) or 5-carboxamidotryptamine (5-CT, Â 0.03-0.3Â nmol) reversed nerve injury-induced tactile allodynia. Intrathecal non-selective (methiothepin, 0.1-0.8Â nmol) and selective (SB-699551, 1-10Â nmol) 5-HT5A receptor antagonists reduced, by ~60% and ~25%, respectively, the antiallodynic effect of 5-HT (100Â nmol) or 5-CT (0.3Â nmol). Moreover, both selective 5-HT1A and 5-HT1B/1D receptor antagonists, WAY-100635 (0.3-1Â nmol) and GR-127935 (0.3-1Â nmol), respectively, partially diminished the antiallodynic effect of 5-HT or 5-CT by about 30%. Injection of antagonists, by themselves, did not affect allodynia. 5-HT5A receptors were expressed in the ipsilateral dorsal lumbar spinal cord and DRG and L5/L6 spinal nerve ligation did not modify 5-HT5A receptor protein expression in those sites. Results suggest that 5-HT5A receptors reduce pain processing in the spinal cord and that 5-HT and 5-CT reduce neuropathic pain through activation of 5-HT5A and 5-HT1A/1B/1D receptors. These receptors could be an important part of the descending pain inhibitory system.
