Impaired neuropathic pain responses in mice lacking the chemokine receptor CCR2 Export

@article{citeulike:6007542, abstract = {10.1073/pnas.1331358100 Mice lacking the chemokine receptor chemotactic cytokine receptor 2 (CCR2) have a marked attenuation of monocyte recruitment in response to various inflammatory stimuli and a reduction of inflammatory lesions in models of demyelinating disease. In the present study, we compared nociceptive responses in inflammatory and neuropathic models of pain in CCR2 knockout and wild-type mice. In acute pain tests, responses were equivalent in CCR2 knockout and wild-type mice. In models of inflammatory pain, CCR2 knockout mice showed a 70\% reduction in phase 2 of the intraplantar formalin-evoked pain response but only a modest (20\^{a}€“30\%) and nonsignificant reduction of mechanical allodynia after intraplantar Freund's adjuvant (CFA). In a model of neuropathic pain, the development of mechanical allodynia was totally abrogated in CCR2 knockout mice. CFA administration induced marked up-regulation of CCR2 mRNA in the skin and a moderate increase in the sciatic nerve and dorsal root ganglia (DRG). In response to nerve ligation, persistent and marked up-regulation of CCR2 mRNA was evident in the nerve and DRG. Disruption of Schwann cells in response to nerve lesion resulted in infiltration of CCR2-positive monocytes/macrophages not only to the neuroma but also to the DRG. Chronic pain also resulted in the appearance of activated CCR2-positive microglia in the spinal cord. Collectively, these data suggest that the recruitment and activation of macrophages and microglia peripherally and in neural tissue may contribute to both inflammatory and neuropathic pain states. Accordingly, blockade of the CCR2 receptor may provide a novel therapeutic modality for the treatment of chronic pain.}, author = {Abbadie, Catherine and Lindia, Jill A. and Cumiskey, Anne M. and Peterson, Larry B. and Mudgett, John S. and Bayne, Ellen K. and DeMartino, Julie A. and MacIntyre, D. Euan and Forrest, Michael J.}, citeulike-article-id = {6007542}, citeulike-linkout-0 = {http://dx.doi.org/10.1073/pnas.1331358100}, citeulike-linkout-1 = {http://www.pnas.org/content/100/13/7947.abstract}, citeulike-linkout-2 = {http://www.pnas.org/content/100/13/7947.full.pdf}, citeulike-linkout-3 = {http://view.ncbi.nlm.nih.gov/pubmed/12808141}, citeulike-linkout-4 = {http://www.hubmed.org/display.cgi?uids=12808141}, day = {24}, doi = {10.1073/pnas.1331358100}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, month = {June}, number = {13}, pages = {7947--7952}, posted-at = {2009-10-25 16:08:19}, priority = {3}, title = {Impaired neuropathic pain responses in mice lacking the chemokine receptor CCR2}, url = {http://dx.doi.org/10.1073/pnas.1331358100}, volume = {100}, year = {2003} }

TY - JOUR ID - citeulike:6007542 L3 - citeulike-article-id:6007542 N2 - 10.1073/pnas.1331358100 Mice lacking the chemokine receptor chemotactic cytokine receptor 2 (CCR2) have a marked attenuation of monocyte recruitment in response to various inflammatory stimuli and a reduction of inflammatory lesions in models of demyelinating disease. In the present study, we compared nociceptive responses in inflammatory and neuropathic models of pain in CCR2 knockout and wild-type mice. In acute pain tests, responses were equivalent in CCR2 knockout and wild-type mice. In models of inflammatory pain, CCR2 knockout mice showed a 70% reduction in phase 2 of the intraplantar formalin-evoked pain response but only a modest (20–30%) and nonsignificant reduction of mechanical allodynia after intraplantar Freund's adjuvant (CFA). In a model of neuropathic pain, the development of mechanical allodynia was totally abrogated in CCR2 knockout mice. CFA administration induced marked up-regulation of CCR2 mRNA in the skin and a moderate increase in the sciatic nerve and dorsal root ganglia (DRG). In response to nerve ligation, persistent and marked up-regulation of CCR2 mRNA was evident in the nerve and DRG. Disruption of Schwann cells in response to nerve lesion resulted in infiltration of CCR2-positive monocytes/macrophages not only to the neuroma but also to the DRG. Chronic pain also resulted in the appearance of activated CCR2-positive microglia in the spinal cord. Collectively, these data suggest that the recruitment and activation of macrophages and microglia peripherally and in neural tissue may contribute to both inflammatory and neuropathic pain states. Accordingly, blockade of the CCR2 receptor may provide a novel therapeutic modality for the treatment of chronic pain. IS - 13 JF - Proceedings of the National Academy of Sciences of the United States of America EP - 7952 TI - Impaired neuropathic pain responses in mice lacking the chemokine receptor CCR2 VL - 100 SP - 7947 AU - Abbadie, Catherine AU - Lindia, Jill AU - Cumiskey, Anne AU - Peterson, Larry AU - Mudgett, John AU - Bayne, Ellen AU - DeMartino, Julie AU - MacIntyre, Euan AU - Forrest, Michael PY - 2003/06/24/ UR - http://dx.doi.org/10.1073/pnas.1331358100 ER -