title: Chemokine Receptor CXCR3 in the Spinal Cord Contributes to Chronic Itch in Mice.
abstract: Recent studies have shown that the chemokine receptor CXCR3 and its ligand CXCL10 in the dorsal root ganglion mediate itch in experimental allergic contact dermatitis (ACD). CXCR3 in the spinal cord also contributes to the maintenance of neuropathic pain. However, whether spinal CXCR3 is involved in acute or chronic itch remains unclear. Here, we report that Cxcr3-/-mice showed normal scratching in acute itch models but reduced scratching in chronic itch models of dry skin and ACD. In contrast, both formalin-induced acute pain and complete Freund's adjuvant-induced chronic inflammatory pain were reduced in Cxcr3-/-mice. In addition, the expression of CXCR3 and CXCL10 was increased in the spinal cord in the dry skin model induced by acetone and diethyl ether followed by water (AEW). Intrathecal injection of a CXCR3 antagonist alleviated AEW-induced itch. Furthermore, touch-elicited itch (alloknesis) after compound 48/80 or AEW treatment was suppressed in Cxcr3-/-mice. Finally, AEW-induced astrocyte activation was inhibited in Cxcr3-/-mice. Taken together, these data suggest that spinal CXCR3 mediates chronic itch and alloknesis, and targeting CXCR3 may provide effective treatment for chronic pruritus.
authors.affiliation: Pain Research Laboratory, Institute of Nautical Medicine, Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong, 226019, China.
authors.forename: Peng-Bo
authors.initials: PB
authors.lastname: Jing
authors.affiliation: Pain Research Laboratory, Institute of Nautical Medicine, Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong, 226019, China.
authors.forename: De-Li
authors.initials: DL
authors.lastname: Cao
authors.affiliation: Pain Research Laboratory, Institute of Nautical Medicine, Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong, 226019, China.
authors.forename: Si-Si
authors.initials: SS
authors.lastname: Li
authors.affiliation: Pain Research Laboratory, Institute of Nautical Medicine, Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong, 226019, China.
authors.forename: Meixuan
authors.initials: M
authors.lastname: Zhu
authors.affiliation: Pain Research Laboratory, Institute of Nautical Medicine, Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong, 226019, China.
authors.forename: Xue-Qiang
authors.initials: XQ
authors.lastname: Bai
authors.affiliation: Pain Research Laboratory, Institute of Nautical Medicine, Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong, 226019, China.
authors.forename: Xiao-Bo
authors.initials: XB
authors.lastname: Wu
authors.affiliation: Pain Research Laboratory, Institute of Nautical Medicine, Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong, 226019, China. gaoyongjing@ntu.edu.cn.|Co-innovation Center of Neuroregeneration, Nantong University, Nantong, 226001, China. gaoyongjing@ntu.edu.cn.
authors.forename: Yong-Jing
authors.initials: YJ
authors.lastname: Gao
mesh_terms: D000081:Acetamides / Q000627:therapeutic use; D000818:Animals; D054357:Chemokine CXCL10 / Q000378:metabolism; D002738:Chloroquine / Q000633:toxicity; D002908:Chronic Disease; D003521:Cyclopropanes / Q000009:adverse effects; D003681:Dehydration / Q000150:complications; D004139:Dinitrofluorobenzene / Q000009:adverse effects; D004195:Disease Models, Animal; D005557:Formaldehyde / Q000633:toxicity; D005620:Freund's Adjuvant / Q000633:toxicity; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects; D010146:Pain / Q000139:chemically induced; D011537:Pruritus / Q000139:chemically induced / Q000473:pathology*; D011743:Pyrimidines / Q000627:therapeutic use; D054367:Receptors, CXCR3 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D012867:Skin / Q000473:pathology; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D013997:Time Factors; D003189:p-Methoxy-N-methylphenethylamine / Q000633:toxicity
chemical_list: D000081:Acetamides; D054357:Chemokine CXCL10; C485433:Cxcl10 protein, mouse; C515188:Cxcr3 protein, mouse; D003521:Cyclopropanes; C501976:NBI-74330; D011743:Pyrimidines; D054367:Receptors, CXCR3; D005557:Formaldehyde; D003189:p-Methoxy-N-methylphenethylamine; D002738:Chloroquine; D005620:Freund's Adjuvant; D004139:Dinitrofluorobenzene; C029402:diphenylcyclopropenone
keywords: Alloknesis; CXCL10; CXCR3; Chronic itch; Dry skin; Spinal cord