Details

Autor(en) / Beteiligte

• BRENCHAT, Alex
• NADAL, Xavier
• BURGUENO, Javier
• ZAMANILLO, Daniel
• HAMON, Michel
• MALDONADO, Rafael
• VELA, José Miguel
• ROMERO, Luz
• OVALLE, Sergio
• MURO, Asunción
• SANCHEZ-ARROYOS, Ricard
• PORTILLO-SALIDO, Enrique
• PUJOL, Marta
• MONTERO, Ana
• CODONY, Xavier

Titel

Pharmacological activation of 5-HT7 receptors reduces nerve injury-induced mechanical and thermal hypersensitivity

Ist Teil von

• Pain (Amsterdam), 2010-06, Vol.149 (3), p.483-494

Ort / Verlag

Philadelphia, PA: Elsevier

Erscheinungsjahr

2010

Quelle

MEDLINE

Beschreibungen/Notizen

• The involvement of the 5-HT(7) receptor in nociception and pain, particularly chronic pain (i.e., neuropathic pain), has been poorly investigated. In the present study, we examined whether the 5-HT(7) receptor participates in some modulatory control of nerve injury-evoked mechanical hypersensitivity and thermal (heat) hyperalgesia in mice. Activation of 5-HT(7) receptors by systemic administration of the selective 5-HT(7) receptor agonist AS-19 (1 and 10mg/kg) exerted a clear-cut reduction of mechanical and thermal hypersensitivities that were reversed by co-administering the selective 5-HT(7) receptor antagonist SB-258719. Interestingly, blocking of 5-HT(7) receptors with SB-258719 (2.5 and 10mg/kg) enhanced mechanical (but not thermal) hypersensitivity in nerve-injured mice and induced mechanical hypersensitivity in sham-operated mice. Effectiveness of the treatment with a 5-HT(7) receptor agonist was maintained after repeated systemic administration: no tolerance to the antiallodynic and antihyperalgesic effects was developed following treatment with the selective 5-HT(7) receptor agonist E-57431 (10mg/kg) twice daily for 11 days. The 5-HT(7) receptor co-localized with GABAergic cells in the dorsal horn of the spinal cord, suggesting that the activation of spinal inhibitory GABAergic interneurons could contribute to the analgesic effects of 5-HT(7) receptor agonists. In addition, a significant increase of 5-HT(7) receptors was found by immunohistochemistry in the ipsilateral dorsal horn of the spinal cord after nerve injury, suggesting a "pain"-triggered regulation of receptor expression. These results support the idea that the 5-HT(7) receptor subtype is involved in the control of pain and point to a new potential use of 5-HT(7) receptor agonists for the treatment of neuropathic pain.