Descending serotonergic facilitation of spinal ERK activation and pain behavior

Abstract
Serotonin (5‐HT) derived from bulbo‐spinal projection is released by nociceptive input into the spinal dorsal horn. Here we report that formalin injection in the paw produced pain behavior (flinching) and phosphorylation of spinal ERK1/2 (P‐ERK1/2, indicating activation) in rats. Depletion of spinal 5‐HT by intrathecal (IT) 5,7‐DHT, a serotonergic neurotoxin, profoundly reduced formalin evoked flinching and the increase in P‐ERK1/2. Ondansetron (a 5‐HT3 receptor antagonist) at IT doses that inhibited flinching also attenuated spinal ERK activation. These findings reveal that primary afferent‐evoked activation of spinal ERK requires the input from an excitatory 5‐HT descending pathway.