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Moreover, changes in the production of nociceptive immune factors are associated with low opioid efficacy in the treatment of neuropathy. Recently, it has been suggested that CC chemokine receptor type 1 (CCR1) signaling is important for nociception. Our study provides evidence that the development of hypersensitivity in rats following chronic constriction injury (CCI) of the sciatic nerve is associated with significant up\u2010regulation of endogenous CCR1 ligands, namely, CCL2, CCL3, CCL4, CCL6, CCL7 and CCL9 in the spinal cord and CCL2, CCL6, CCL7 and CCL9 in dorsal root ganglia (DRG). We showed that single and repeated intrathecal administration of J113863 (an antagonist of CCR1) attenuated mechanical and thermal hypersensitivity. Moreover, repeated administration of a CCR1 antagonist enhanced the analgesic properties of morphine and buprenorphine after CCI. Simultaneously, repeated administration of J113863 reduced the protein levels of IBA\u20101 in the spinal cord and MPO and CD4 in the DRG and, as a consequence, the level of pronociceptive factors, such as interleukin\u20101<jats:italic>\u03b2<\/jats:italic> (IL\u20101<jats:italic>\u03b2<\/jats:italic>), IL\u20106 and IL\u201018. The data obtained provide evidence that CCR1 blockade reduces hypersensitivity and increases opioid\u2010induced analgesia through the modulation of neuroimmune interactions.<\/jats:p>","DOI":"10.1111\/imm.13172","type":"journal-article","created":{"date-parts":[[2020,1,10]],"date-time":"2020-01-10T06:12:09Z","timestamp":1578636729000},"page":"413-428","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["The blockade of CC chemokine receptor type 1 influences the level of nociceptive factors and enhances opioid analgesic potency in a rat model of neuropathic pain"],"prefix":"10.1111","volume":"159","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8091-4974","authenticated-orcid":false,"given":"Katarzyna","family":"Pawlik","sequence":"first","affiliation":[{"name":"Department of Pain Pharmacology Maj Institute of Pharmacology Polish Academy of Sciences Krakow Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2091-2678","authenticated-orcid":false,"given":"Anna","family":"Piotrowska","sequence":"additional","affiliation":[{"name":"Department of Pain Pharmacology Maj Institute of Pharmacology Polish Academy of Sciences Krakow Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0119-5749","authenticated-orcid":false,"given":"Klaudia","family":"Kwiatkowski","sequence":"additional","affiliation":[{"name":"Department of Pain Pharmacology Maj Institute of Pharmacology Polish Academy of Sciences Krakow Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6147-1576","authenticated-orcid":false,"given":"Katarzyna","family":"Ciapa\u0142a","sequence":"additional","affiliation":[{"name":"Department of Pain Pharmacology Maj Institute of Pharmacology Polish Academy of Sciences Krakow Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4366-6577","authenticated-orcid":false,"given":"Katarzyna","family":"Popiolek\u2010Barczyk","sequence":"additional","affiliation":[{"name":"Department of Pain Pharmacology Maj Institute of Pharmacology Polish Academy of Sciences Krakow Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1579-3643","authenticated-orcid":false,"given":"Wioletta","family":"Makuch","sequence":"additional","affiliation":[{"name":"Department of Pain Pharmacology Maj Institute of Pharmacology Polish Academy of Sciences Krakow Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1986-7205","authenticated-orcid":false,"given":"Joanna","family":"Mika","sequence":"additional","affiliation":[{"name":"Department of Pain Pharmacology Maj Institute of Pharmacology Polish Academy of Sciences Krakow Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,2,5]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2017.2"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s42399-018-0009-4"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.18773\/austprescr.2018.022"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd1852"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2017.101"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2014.09.020"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.2174\/0929867323666160607120124"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.sjpain.2017.08.002"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20122904"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn1992"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/480739"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41386-018-0115-8"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11481-017-9729-6"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2016.04.024"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pnpbp.2015.07.005"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1116"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1023\/B:NERE.0000021246.96864.89"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2016.09.010"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0706912"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2013.06.034"},{"key":"e_1_2_8_22_1","unstructured":"HencI RodzinnejEB\u2010FM. 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