{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T09:55:57Z","timestamp":1793786157989,"version":"4.6.1"},"reference-count":47,"publisher":"Wiley","issue":"21","license":[{"start":{"date-parts":[[2014,9,5]],"date-time":"2014-09-05T00:00:00Z","timestamp":1409875200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Italian Ministry of University and Scientific Research","award":["20099F3XPM_003"],"award-info":[{"award-number":["20099F3XPM_003"]}]},{"DOI":"10.13039\/501100004271","name":"Sapienza University of Rome","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004271","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2014,11]]},"abstract":"<jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>Chemokines are involved in neuroinflammation and contribute to chronic pain processing. The new chemokine prokineticin 2 (<jats:styled-content style=\"fixed-case\">PROK2<\/jats:styled-content>) and its receptors (<jats:styled-content style=\"fixed-case\">PKR<jats:sub>1<\/jats:sub><\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">PKR<jats:sub>2<\/jats:sub><\/jats:styled-content>) have a role in inflammatory pain and immunomodulation. In the present study, we investigated the involvement of <jats:styled-content style=\"fixed-case\">PROK2<\/jats:styled-content> and its receptors in neuropathic pain.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Effects of single, intrathecal, perineural and s.c. injections of the <jats:styled-content style=\"fixed-case\">PKR<\/jats:styled-content> antagonist <jats:styled-content style=\"fixed-case\">PC1<\/jats:styled-content>, or of 1 week s.c. treatment, on thermal hyperalgesia and tactile allodynia was evaluated in mice with chronic constriction of the sciatic nerve (<jats:styled-content style=\"fixed-case\">CCI<\/jats:styled-content>). Expression and localization of <jats:styled-content style=\"fixed-case\">PROK2<\/jats:styled-content> and of its receptors at peripheral and central level was evaluated 10 days after <jats:styled-content style=\"fixed-case\">CCI<\/jats:styled-content>, following treatment for 1 week with saline or PC1. <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20101\u03b2 and <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201010 levels, along with glia activation, were evaluated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Subcutaneous, intrathecal and perineural <jats:styled-content style=\"fixed-case\">PC1<\/jats:styled-content> acutely abolished the <jats:styled-content style=\"fixed-case\">CCI<\/jats:styled-content>\u2010induced hyperalgesia and allodynia. At 10 days after <jats:styled-content style=\"fixed-case\">CCI, PROK2<\/jats:styled-content> and its receptor <jats:styled-content style=\"fixed-case\">PKR<jats:sub>2<\/jats:sub><\/jats:styled-content> were up\u2010regulated in nociceptors, in <jats:styled-content style=\"fixed-case\">S<\/jats:styled-content>chwann cells and in activated astrocytes of the spinal cord. Therapeutic treatment with <jats:styled-content style=\"fixed-case\">PC1<\/jats:styled-content> (s.c., 1 week) alleviated established thermal hyperalgesia and allodynia, reduced the injury\u2010induced overexpression of <jats:styled-content style=\"fixed-case\">PROK2<\/jats:styled-content>, significantly blunted nerve injury\u2010induced microgliosis and astrocyte activation in the spinal cord and restored the physiological levels of proinflammatory and anti\u2010inflammatory cytokines in periphery and in spinal cord.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and Implications<\/jats:title><jats:p>The prokineticin system contributes to pain modulation via neuron\u2013glia interaction. Sustained inhibition of the prokineticin system, at peripheral or central levels, blocked both pain symptoms and some events underlying disease progression.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.12793","type":"journal-article","created":{"date-parts":[[2014,6,6]],"date-time":"2014-06-06T02:57:01Z","timestamp":1402023421000},"page":"4850-4865","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":52,"title":["Controlling the activation of the <scp>B<\/scp>v8\/prokineticin system reduces neuroinflammation and abolishes thermal and tactile hyperalgesia in neuropathic animals"],"prefix":"10.1111","volume":"171","author":[{"given":"D","family":"Maftei","sequence":"first","affiliation":[{"name":"Department of Physiology and Pharmacology \u2018Vittorio Erspamer\u2019 University of Rome  Rome 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