Blockade of 5-HT7 receptors reduces tactile allodynia in the rat

• Published in: Pharmacology, biochemistry and behavior Vol. 99; no. 4; pp. 591 - 597
• Main Authors: Amaya-Castellanos, Evelyn, Pineda-Farias, Jorge B., Castañeda-Corral, Gabriela, Vidal-Cantú, Guadalupe C., Murbartián, Janet, Rocha-González, Héctor I., Granados-Soto, Vinicio
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Inc 01.10.2011; Elsevier
• Subjects: 5-HT7 receptors; Analgesics; Animals; Area Under Curve; Biological and medical sciences; Blotting, Western; Cranial nerves. Spinal roots. Peripheral nerves. Autonomic nervous system. Gustation. Olfaction; Data Interpretation, Statistical; Female; Functional Laterality - drug effects; Functional Laterality - physiology; Hyperalgesia - drug therapy; Hyperalgesia - psychology; Injections, Intraperitoneal; Injections, Spinal; Ligation; Medical sciences; Nervous system (semeiology, syndromes); Neuralgia - drug therapy; Neurology; Neuropathic pain; Pain Measurement - drug effects; Phenols - pharmacology; Physical Stimulation; Posterior Horn Cells - metabolism; Rats; Rats, Wistar; Receptors, Serotonin - drug effects; Receptors, Serotonin - metabolism; SB-269970; Serotonin; Serotonin Antagonists - pharmacology; Spinal Nerves; Spinal processing; Sulfonamides - pharmacology; Spinal processing; 5-HT7 receptors; Serotonin; SB-269970; Neuropathic pain; Allodynia; Nervous system diseases; Rat; receptors; Rodentia; 5-HT7 serotonin receptor; Tactile sensitivity; Vertebrata; Mammalia; Animal; Neurotransmitter; Neuralgia; Neurological disorder; 5-HT
• ISSN: 0091-3057; 1873-5177
• DOI: 10.1016/j.pbb.2011.06.005

This study assessed the role of systemic and spinal 5-HT7 receptors on rats submitted to spinal nerve injury. In addition, the 5-HT7 receptors level in dorsal root ganglion and spinal cord was also determined. Tactile allodynia was induced by L5/L6 spinal nerve ligation. Systemic (0.01–10mg/kg) or spinal (0.3–30μg) administration of the selective 5-HT7 receptor antagonist SB-269970 but not vehicle reduced in a dose-dependent manner established tactile allodynia. This effect was maintained for about 6h. SB-269970 was more potent and effective by the spinal administration route than through systemic injection. Spinal nerve ligation reduced expression of 5-HT7 receptors in the ipsilateral but not contralateral dorsal root ganglia. Moreover, 5-HT7 receptor levels were lower in the ipsilateral dorsal spinal cord of neuropathic rats compared to naïve and sham rats. No changes in the receptor levels were observed in the contralateral dorsal spinal cord and in both regions of the ventral spinal cord. Data suggest that spinal 5-HT7 receptors play a pronociceptive role in neuropathic rats. Results also indicate that spinal nerve injury leads to a reduced 5-HT7 receptors level in pain processing-related areas which may result from its nociceptive role in this model. Data suggest that selective 5-HT7 receptor antagonists may function as analgesics in nerve injury pain states. ► Intrathecal injection of SB-269970 reduces tactile allodynia in rats. ► Systemic administration of SB-269970 reduces tactile allodynia in rats. ► Spinal nerve ligation reduces expression of 5-HT7 receptors in DRG and spinal cord.