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

This study assessed the role of systemic and spinal 5-HT₇ receptors on rats submitted to spinal nerve injury. In addition, the 5-HT ₇ receptors level in dorsal root ganglion and spinal cord was also determined. Tactile allodynia was induced by L5/L6 spinal nerve ligation. Systemic (0.01-10 mg/kg) or spinal (0.3-30 μg) 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 6 h. 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.