Descending serotonergic facilitation of spinal ERK activation and pain behavior.
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.
Svensson
Camilla I
CI
Department of Anesthesiology, University of California - San Diego, 9500 Gilman drive, La Jolla, CA 92093-0818, USA.
Tran
Thao K
TK
Fitzsimmons
Bethany
B
Yaksh
Tony L
TL
Hua
Xiao-Ying
XY
D000818:Animals; D004789:Enzyme Activation / Q000187:drug effects; D005528:Foot; D005557:Formaldehyde / Q000494:pharmacology; D006930:Hyperalgesia / Q000201:enzymology; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010146:Pain / Q000201:enzymology* / Q000503:physiopathology*; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000172:deficiency / Q000378:metabolism*; D058831:Serotonin 5-HT3 Receptor Antagonists; D013116:Spinal Cord / Q000201:enzymology*
D058831:Serotonin 5-HT3 Receptor Antagonists; D005557:Formaldehyde; D012701:Serotonin; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3