TY - JOUR
T1 - A peptide c-Jun N-terminal kinase (JNK) inhibitor blocks mechanical allodynia after spinal nerve ligation
T2 - Respective roles of JNK activation in primary sensory neurons and spinal astrocytes for neuropathic pain development and maintenance
AU - Zhuang, Zhi Ye
AU - Wen, Yeong Ray
AU - Zhang, De Ren
AU - Borsello, Tiziana
AU - Bonny, Christophe
AU - Strichartz, Gary R.
AU - Decosterd, Isabelle
AU - Ji, Ru Rong
PY - 2006/3/29
Y1 - 2006/3/29
N2 - Optimal management of neuropathic pain is a major clinical challenge. We investigated the involvement of c-Jun N-terminal kinase (JNK) in neuropathic pain produced by spinal nerve ligation (SNL) (L5). SNL induced a slow (>3 d) and persistent (>21 d) activation of JNK, in particular JNK1, in GFAP-expressing astrocytes in the spinal cord. In contrast, p38 mitogen-activated protein kinase activation was found in spinal microglia after SNL, which had fallen to near basal level by 21 d. Intrathecal infusion of a JNK peptide inhibitor, D-JNKI-1, did not affect normal pain responses but potently prevented and reversed SNL-induced mechanical allodynia, a major symptom of neuropathic pain. Intrathecal D-JNKI-1 also suppressed SNL-induced phosphorylation of the JNK substrate, c-Jun, in spinal astrocytes. However, SNL-induced upregulation of GFAP was not attenuated by spinal D-JNKI-1 infusion. Furthermore, SNL induced a rapid (
AB - Optimal management of neuropathic pain is a major clinical challenge. We investigated the involvement of c-Jun N-terminal kinase (JNK) in neuropathic pain produced by spinal nerve ligation (SNL) (L5). SNL induced a slow (>3 d) and persistent (>21 d) activation of JNK, in particular JNK1, in GFAP-expressing astrocytes in the spinal cord. In contrast, p38 mitogen-activated protein kinase activation was found in spinal microglia after SNL, which had fallen to near basal level by 21 d. Intrathecal infusion of a JNK peptide inhibitor, D-JNKI-1, did not affect normal pain responses but potently prevented and reversed SNL-induced mechanical allodynia, a major symptom of neuropathic pain. Intrathecal D-JNKI-1 also suppressed SNL-induced phosphorylation of the JNK substrate, c-Jun, in spinal astrocytes. However, SNL-induced upregulation of GFAP was not attenuated by spinal D-JNKI-1 infusion. Furthermore, SNL induced a rapid (
KW - Dorsal root ganglion
KW - Glia
KW - MAP kinase
KW - Nerve injury
KW - Neuropathy
KW - Spinal cord
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UR - http://www.scopus.com/inward/citedby.url?scp=33645460235&partnerID=8YFLogxK
U2 - 10.1523/JNEUROSCI.5290-05.2006
DO - 10.1523/JNEUROSCI.5290-05.2006
M3 - Article
C2 - 16571763
AN - SCOPUS:33645460235
VL - 26
SP - 3551
EP - 3560
JO - Journal of Neuroscience
JF - Journal of Neuroscience
SN - 0270-6474
IS - 13
ER -