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.
Publication types
-
Research Support, N.I.H., Extramural
MeSH terms
-
Animals
-
Enzyme Activation / drug effects
-
Foot
-
Formaldehyde / pharmacology
-
Hyperalgesia / enzymology
-
Male
-
Mitogen-Activated Protein Kinase 1 / antagonists & inhibitors
-
Mitogen-Activated Protein Kinase 1 / metabolism*
-
Mitogen-Activated Protein Kinase 3 / antagonists & inhibitors
-
Mitogen-Activated Protein Kinase 3 / metabolism*
-
Pain / enzymology*
-
Pain / physiopathology*
-
Phosphorylation / drug effects
-
Rats
-
Rats, Sprague-Dawley
-
Serotonin / deficiency
-
Serotonin / metabolism*
-
Serotonin 5-HT3 Receptor Antagonists
-
Spinal Cord / enzymology*
Substances
-
Serotonin 5-HT3 Receptor Antagonists
-
Formaldehyde
-
Serotonin
-
Mitogen-Activated Protein Kinase 1
-
Mitogen-Activated Protein Kinase 3