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Reduced inflammatory and neuropathic pain and decreased spinal microglial response in fractalkine receptor (CX3CR1) knockout mice.
J Neurochem. 2010 Aug; 114(4):1143-57.JN

Abstract

The chemokine fractalkine (FKN) is a critical mediator of spinal neuronal-microglial communication in chronic pain. Mature FKN is enzymatically cleaved from neuronal membranes and activation of its receptor, CX3CR1, which is expressed by microglia, induces phosphorylation of p38 MAPK. We used CX3CR1 knockout (KO) mice to examine pain behaviour in the absence of FKN signalling. Naive CX3CR1 KO mice had normal responses to acute noxious stimuli. However, KO mice showed deficits in inflammatory and neuropathic nociceptive responses. After intraplantar zymosan, KO mice did not display thermal hyperalgesia, whereas mechanical allodynia developed fully. In the partial sciatic nerve ligation model of neuropathic pain, both mechanical allodynia and thermal hyperalgesia were less severe in KO mice than in wild-types (WT). Dorsal horn Iba1 immunostaining and phosphorylation of p38 MAPK increased after injury in WT controls but not in KO animals. In WT mice, inflammation and nerve injury increased spinal cord CX3CR1 and FKN expression. FKN protein was also increased in KO mice following inflammation but not after neuropathy, suggesting the FKN/CX3CR1 system is differently affected in the two pain models. Loss of FKN/CX3CR1 neuroimmune communication attenuates hyperalgesia and allodynia in a modality-dependent fashion highlighting the complex nature of microglial response in pathological pain models.

Authors+Show Affiliations

Wolfson Centre for Age-Related Diseases, King's College London, London, UK.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

20524966

Citation

Staniland, Amelia A., et al. "Reduced Inflammatory and Neuropathic Pain and Decreased Spinal Microglial Response in Fractalkine Receptor (CX3CR1) Knockout Mice." Journal of Neurochemistry, vol. 114, no. 4, 2010, pp. 1143-57.
Staniland AA, Clark AK, Wodarski R, et al. Reduced inflammatory and neuropathic pain and decreased spinal microglial response in fractalkine receptor (CX3CR1) knockout mice. J Neurochem. 2010;114(4):1143-57.
Staniland, A. A., Clark, A. K., Wodarski, R., Sasso, O., Maione, F., D'Acquisto, F., & Malcangio, M. (2010). Reduced inflammatory and neuropathic pain and decreased spinal microglial response in fractalkine receptor (CX3CR1) knockout mice. Journal of Neurochemistry, 114(4), 1143-57. https://doi.org/10.1111/j.1471-4159.2010.06837.x
Staniland AA, et al. Reduced Inflammatory and Neuropathic Pain and Decreased Spinal Microglial Response in Fractalkine Receptor (CX3CR1) Knockout Mice. J Neurochem. 2010;114(4):1143-57. PubMed PMID: 20524966.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Reduced inflammatory and neuropathic pain and decreased spinal microglial response in fractalkine receptor (CX3CR1) knockout mice. AU - Staniland,Amelia A, AU - Clark,Anna K, AU - Wodarski,Rachel, AU - Sasso,Oscar, AU - Maione,Francesco, AU - D'Acquisto,Fulvio, AU - Malcangio,Marzia, Y1 - 2010/05/28/ PY - 2010/6/8/entrez PY - 2010/6/8/pubmed PY - 2010/10/7/medline SP - 1143 EP - 57 JF - Journal of neurochemistry JO - J Neurochem VL - 114 IS - 4 N2 - The chemokine fractalkine (FKN) is a critical mediator of spinal neuronal-microglial communication in chronic pain. Mature FKN is enzymatically cleaved from neuronal membranes and activation of its receptor, CX3CR1, which is expressed by microglia, induces phosphorylation of p38 MAPK. We used CX3CR1 knockout (KO) mice to examine pain behaviour in the absence of FKN signalling. Naive CX3CR1 KO mice had normal responses to acute noxious stimuli. However, KO mice showed deficits in inflammatory and neuropathic nociceptive responses. After intraplantar zymosan, KO mice did not display thermal hyperalgesia, whereas mechanical allodynia developed fully. In the partial sciatic nerve ligation model of neuropathic pain, both mechanical allodynia and thermal hyperalgesia were less severe in KO mice than in wild-types (WT). Dorsal horn Iba1 immunostaining and phosphorylation of p38 MAPK increased after injury in WT controls but not in KO animals. In WT mice, inflammation and nerve injury increased spinal cord CX3CR1 and FKN expression. FKN protein was also increased in KO mice following inflammation but not after neuropathy, suggesting the FKN/CX3CR1 system is differently affected in the two pain models. Loss of FKN/CX3CR1 neuroimmune communication attenuates hyperalgesia and allodynia in a modality-dependent fashion highlighting the complex nature of microglial response in pathological pain models. SN - 1471-4159 UR - https://www.unboundmedicine.com/medline/citation/20524966/Reduced_inflammatory_and_neuropathic_pain_and_decreased_spinal_microglial_response_in_fractalkine_receptor__CX3CR1__knockout_mice_ L2 - https://doi.org/10.1111/j.1471-4159.2010.06837.x DB - PRIME DP - Unbound Medicine ER -