The c-Jun N-terminal kinase 1 (JNK1) in spinal astrocytes is required for the maintenance of bilateral mechanical allodynia under a persistent inflammatory pain condition
- 1 February 2010
- journal article
- Published by Ovid Technologies (Wolters Kluwer Health) in Pain
- Vol. 148 (2), 309-319
- https://doi.org/10.1016/j.pain.2009.11.017
Abstract
Peripheral inflammation induces persistent central sensitization characterized by mechanical allodynia and heat hyperalgesia that are mediated by distinct mechanisms. Compared to well-demonstrated mechanisms of heat hyperalgesia, mechanisms underlying the development of mechanical allodynia and contralateral pain are incompletely known. In this study, we investigated the distinct role of spinal JNK in heat hyperalgesia, mechanical allodynia, and contralateral pain in an inflammatory pain model. Intraplantar injection of complete Freund's adjuvant (CFA) induced bilateral mechanical allodynia but unilateral heat hyperalgesia. CFA also induced a bilateral activation (phosphorylation) of JNK in the spinal cord, and the phospho JNK1 (pJNK1) levels were much higher than that of pJNK2. Notably, both pJNK and JNK1 were expressed in GFAP-positive astrocytes. Intrathecal infusion of a selective peptide inhibitor of JNK, D-JNKI-1, starting before inflammation via an osmotic pump, reduced CFA-induced mechanical allodynia in the maintenance phase but had no effect on CFA-induced heat hyperalgesia. A bolus intrathecal injection of D-JNKI-1 or SP600126, a small molecule inhibitor of JNK also reversed mechanical allodynia bilaterally. In contrast, peripheral (intraplantar) administration of D-JNKI-1 reduced the induction of CFA-induced heat hyperalgesia but did not change mechanical allodynia. Finally, CFA-induced bilateral mechanical allodynia was attenuated in mice lacking JNK1 but not JNK2. Taken together, our data suggest that spinal JNK, in particular JNK1 plays an important role in the maintenance of persistent inflammatory pain. Our findings also reveal a unique role of JNK1 and astrocyte network in regulating tactile allodynia and contralateral pain.Keywords
This publication has 72 references indexed in Scilit:
- MAP kinase and painBrain Research Reviews, 2009
- JNK-Induced MCP-1 Production in Spinal Cord Astrocytes Contributes to Central Sensitization and Neuropathic PainJournal of Neuroscience, 2009
- COX2 in CNS neural cells mediates mechanical inflammatory pain hypersensitivity in miceJCI Insight, 2009
- Pathological and protective roles of glia in chronic painNature Reviews Neuroscience, 2009
- Activation of the Neuronal Extracellular Signal-Regulated Kinase 2 in the Spinal Cord Dorsal Horn Is Required for Complete Freund's Adjuvant-Induced Pain HypersensitivityJournal of Neuroscience, 2008
- Activation of JNK pathway in persistent painNeuroscience Letters, 2008
- Glycine Inhibitory Dysfunction Turns Touch into Pain through PKCgamma InterneuronsPLOS ONE, 2007
- Glial–Cytokine–Neuronal Interactions Underlying the Mechanisms of Persistent PainJournal of Neuroscience, 2007
- Possible role of spinal astrocytes in maintaining chronic pain sensitization: review of current evidence with focus on bFGF/JNK pathwayNeuron Glia Biology, 2006
- MAPK activation in nociceptive neurons and pain hypersensitivityLife Sciences, 2004