PMID- 25354468 OWN - NLM STAT- MEDLINE DCOM- 20150910 LR - 20211021 IS - 1097-4547 (Electronic) IS - 0360-4012 (Print) IS - 0360-4012 (Linking) VI - 93 IP - 3 DP - 2015 Mar TI - Scratching activates microglia in the mouse spinal cord. PG - 466-74 LID - 10.1002/jnr.23501 [doi] AB - This study tested the hypothesis that repetitive scratching provoked by two known pruritogens, compound 48/80 and 5'-guanidinonaltrindole (GNTI), is accompanied by activation of microglial cells in the mouse spinal cord. Immunohistochemical studies revealed that the complement receptor 3, also known as cluster determinant 11b (CD11b), a cell surface marker of microglial cells, was upregulated in the spinal cord 10-30 min after a subcutaneous (s.c.) injection of compound 48/80 (50 mug/100 mul) or GNTI (0.3 mg/kg) to the back of the mouse neck. Numerous intensely labeled CD11b-immunoreactive (CD11b-ir) cells, with the appearance of hypertrophic reactive microglia, were distributed throughout the gray and white matter. In contrast, weakly labeled CD11b-ir cells were distributed in the spinal cord from mice injected with saline. Western blots showed that CD11b expression levels were significantly increased in spinal cords of mice injected s.c. with either pruritogen, reached a peak response in about 30 min, and declined to about the basal level in the ensuing 60 min. In addition, phospho-p38 (p-p38) but not p38 levels were upregulated in spinal cords from mice injected with compound 48/80 or GNTI, with a time course parallel to that of CD11b expression. Pretreatment of the mice with nalfurafine (20 microg/kg; s.c.), a kappa-opioid receptor agonist that has been shown to suppress scratching, reduced CD11b and p-p38 expression induced by either pruritogen. The results demonstrate, for the first time, that scratch behavior induced by the pruritogens GNTI and compound 48/80 is accompanied by a parallel activation of microglial cells in the spinal cord. CI - (c) 2014 Wiley Periodicals, Inc. FAU - Zhang, Ying AU - Zhang Y AD - Department of Pharmacology, Temple University School of Medicine, Philadelphia, Pennsylvania; Department of Pathophysiology, Kunming Medical University, Kunming, China. FAU - Dun, Siok L AU - Dun SL FAU - Chen, Yi-Hung AU - Chen YH FAU - Luo, Jin J AU - Luo JJ FAU - Cowan, Alan AU - Cowan A FAU - Dun, Nae J AU - Dun NJ LA - eng GR - P30 DA013429/DA/NIDA NIH HHS/United States GR - R37 NS018710/NS/NINDS NIH HHS/United States GR - P30DA13429/DA/NIDA NIH HHS/United States GR - R37NS18710/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20141030 PL - United States TA - J Neurosci Res JT - Journal of neuroscience research JID - 7600111 RN - 0 (17-cyclopropylmethyl-6,7-didehydro-4,5-epoxy-5'-guanidinyl-3,14-dihydroxyindolo(2',3'-6,7)morphinan) RN - 0 (CD11b Antigen) RN - 0 (Guanidines) RN - 0 (Morphinans) RN - 4091-50-3 (p-Methoxy-N-methylphenethylamine) RN - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases) SB - IM MH - Animals MH - Behavior, Animal/*physiology MH - CD11b Antigen/*metabolism MH - Guanidines MH - Male MH - Mice MH - Microglia/*metabolism MH - Morphinans MH - Phosphorylation MH - Pruritus/chemically induced/*metabolism MH - Spinal Cord/*metabolism MH - Up-Regulation MH - p-Methoxy-N-methylphenethylamine MH - p38 Mitogen-Activated Protein Kinases/metabolism PMC - PMC4293236 MID - NIHMS638099 OTO - NOTNLM OT - GNTI OT - compound 48/80 OT - glia OT - itch OT - nalfurafine OT - p38 OT - phospho-p38 EDAT- 2014/10/31 06:00 MHDA- 2015/09/12 06:00 PMCR- 2016/03/01 CRDT- 2014/10/31 06:00 PHST- 2014/05/30 00:00 [received] PHST- 2014/08/26 00:00 [revised] PHST- 2014/09/24 00:00 [accepted] PHST- 2014/10/31 06:00 [entrez] PHST- 2014/10/31 06:00 [pubmed] PHST- 2015/09/12 06:00 [medline] PHST- 2016/03/01 00:00 [pmc-release] AID - 10.1002/jnr.23501 [doi] PST - ppublish SO - J Neurosci Res. 2015 Mar;93(3):466-74. doi: 10.1002/jnr.23501. Epub 2014 Oct 30.