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Interleukin-6 induces microglial CX3CR1 expression in the spinal cord after peripheral nerve injury through the activation of p38 MAPK.
Eur J Pain. 2010 Aug; 14(7):682.e1-12.EJ

Abstract

Peripheral nerve injury leading to neuropathic pain induces the upregulation of interleukin (IL)-6 and microglial CX3CR1 expression, and activation of p38 mitogen-activated protein kinase (MAPK) in the spinal cord. Here, we investigated whether IL-6 regulates CX3CR1 expression through p38 MAPK activation in the spinal cord in rats with chronic constriction injury (CCI) of the sciatic nerve. Similar temporal changes in the expression of IL-6, phosphorylated p38 MAPK and CX3CR1 were observed following CCI. The increases in CX3CR1 expression, p38 MAPK activation and pain behavior after CCI were suppressed by blocking IL-6 action with a neutralizing antibody, while they were enhanced by supplying exogenous recombinant rat IL-6 (rrIL-6). rrIL-6 also induced increases in spinal CX3CR1 expression, p38 MAPK activation and pain behavior in naive rats without nerve injury. Furthermore, treatment with the p38 MAPK-specific inhibitor, SB203580, suppressed the increase in CX3CR1 expression induced by CCI or rrIL-6 treatment. Finally, blocking CX3CR1 or p38 MAPK activation prevented the development of mechanical allodynia and thermal hyperalgesia induced by CCI or rrIL-6 treatment. These results suggest a new mechanism of neuropathic pain, in which IL-6 induces microglial CX3CR1 expression in the spinal cord through p38 MAPK activation, enhancing the responsiveness of microglia to fractalkine in the spinal cord, thus playing an important role in neuropathic pain after peripheral nerve injury.

Authors+Show Affiliations

Department of Anatomy, School of Medicine, Kyungpook National University, 2-101 Dongin-Dong, Daegu 700-422, South Korea.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19959384

Citation

Lee, Kyung-Min, et al. "Interleukin-6 Induces Microglial CX3CR1 Expression in the Spinal Cord After Peripheral Nerve Injury Through the Activation of P38 MAPK." European Journal of Pain (London, England), vol. 14, no. 7, 2010, pp. 682.e1-12.
Lee KM, Jeon SM, Cho HJ. Interleukin-6 induces microglial CX3CR1 expression in the spinal cord after peripheral nerve injury through the activation of p38 MAPK. Eur J Pain. 2010;14(7):682.e1-12.
Lee, K. M., Jeon, S. M., & Cho, H. J. (2010). Interleukin-6 induces microglial CX3CR1 expression in the spinal cord after peripheral nerve injury through the activation of p38 MAPK. European Journal of Pain (London, England), 14(7), e1-12. https://doi.org/10.1016/j.ejpain.2009.10.017
Lee KM, Jeon SM, Cho HJ. Interleukin-6 Induces Microglial CX3CR1 Expression in the Spinal Cord After Peripheral Nerve Injury Through the Activation of P38 MAPK. Eur J Pain. 2010;14(7):682.e1-12. PubMed PMID: 19959384.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Interleukin-6 induces microglial CX3CR1 expression in the spinal cord after peripheral nerve injury through the activation of p38 MAPK. AU - Lee,Kyung-Min, AU - Jeon,Sang-Min, AU - Cho,Hee-Jung, Y1 - 2009/12/02/ PY - 2009/06/18/received PY - 2009/09/26/revised PY - 2009/10/20/accepted PY - 2009/12/5/entrez PY - 2009/12/5/pubmed PY - 2010/10/26/medline SP - 682.e1 EP - 12 JF - European journal of pain (London, England) JO - Eur J Pain VL - 14 IS - 7 N2 - Peripheral nerve injury leading to neuropathic pain induces the upregulation of interleukin (IL)-6 and microglial CX3CR1 expression, and activation of p38 mitogen-activated protein kinase (MAPK) in the spinal cord. Here, we investigated whether IL-6 regulates CX3CR1 expression through p38 MAPK activation in the spinal cord in rats with chronic constriction injury (CCI) of the sciatic nerve. Similar temporal changes in the expression of IL-6, phosphorylated p38 MAPK and CX3CR1 were observed following CCI. The increases in CX3CR1 expression, p38 MAPK activation and pain behavior after CCI were suppressed by blocking IL-6 action with a neutralizing antibody, while they were enhanced by supplying exogenous recombinant rat IL-6 (rrIL-6). rrIL-6 also induced increases in spinal CX3CR1 expression, p38 MAPK activation and pain behavior in naive rats without nerve injury. Furthermore, treatment with the p38 MAPK-specific inhibitor, SB203580, suppressed the increase in CX3CR1 expression induced by CCI or rrIL-6 treatment. Finally, blocking CX3CR1 or p38 MAPK activation prevented the development of mechanical allodynia and thermal hyperalgesia induced by CCI or rrIL-6 treatment. These results suggest a new mechanism of neuropathic pain, in which IL-6 induces microglial CX3CR1 expression in the spinal cord through p38 MAPK activation, enhancing the responsiveness of microglia to fractalkine in the spinal cord, thus playing an important role in neuropathic pain after peripheral nerve injury. SN - 1532-2149 UR - https://www.unboundmedicine.com/medline/citation/19959384/Interleukin_6_induces_microglial_CX3CR1_expression_in_the_spinal_cord_after_peripheral_nerve_injury_through_the_activation_of_p38_MAPK_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1090-3801(09)00235-3 DB - PRIME DP - Unbound Medicine ER -