Essential role of the synaptic vesicle protein synapsin II in formalin-induced hyperalgesia and glutamate release in the spinal cord.
The synaptic vesicle protein synapsin II plays an important role in the regulation of neurotransmitter release and synaptic plasticity. Here, we investigated its involvement in the synaptic transmission of nociceptive signals in the spinal cord and the development of pain hypersensitivity. We show that synapsin II is predominantly expressed in terminals and neuronal fibers in superficial laminae of the dorsal horn (laminae I-II). Formalin injection into a mouse hindpaw normally causes an immediate and strong release of glutamate in the dorsal horn. In synapsin II deficient mice this glutamate release is almost completely missing. This is associated with reduced nociceptive behavior in the formalin test and in the zymosan-induced paw inflammation model. In addition, the formalin evoked increase in the number of c-Fos IR neurons is significantly reduced in synapsin II knockout mice. Touch perception and motor coordination, however, are normal indicating that synapsin II deficiency does not generally disrupt sensory and/or motor functions. Antisense-mediated transient knockdown of synapsin II in the spinal cord of adult animals also reduced the nociceptive behavior. As the antisense effect is independent of a potential role of synapsin II during development we suggest that the hypoalgesia in synapsin II deficient mice does involve a direct 'pain-facilitating' effect of synapsin II and is not essentially dependent on potentially occurring developmental alterations. The distinctive role of synapsin II for pain signaling probably results from its specific localization and possibly from a specific control of glutamate release.
Schmidtko
Achim
A
Pharmazentrum Frankfurt, Institut für Klinische Pharmakologie/ZAFES, Klinikum der Johann Wolfgang Goethe-Universität Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany.
Del Turco
Domenico
D
Coste
Ovidiu
O
Ehnert
Corina
C
Niederberger
Ellen
E
Ruth
Peter
P
Deller
Thomas
T
Geisslinger
Gerd
G
Tegeder
Irmgard
I
D000818:Animals; D005260:Female; D005557:Formaldehyde; D018698:Glutamic Acid / Q000378:metabolism*; D006930:Hyperalgesia / Q000139:chemically induced / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018377:Neurotransmitter Agents / Q000378:metabolism; D020671:Posterior Horn Cells / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000378:metabolism*; D016704:Synapsins / Q000378:metabolism*; D009435:Synaptic Transmission; D013572:Synaptic Vesicles / Q000187:drug effects / Q000378:metabolism*
D018377:Neurotransmitter Agents; D016704:Synapsins; D005557:Formaldehyde; D018698:Glutamic Acid