title: The role of keratinocyte-derived chemokine (KC) on hyperalgesia caused by peripheral nerve injury in mice.
abstract: Chemokines are associated with both inflammatory and immune responses and play an important role in the pathophysiological process associated with neuropathic pain following peripheral nerve injury. Here, we investigated the involvement of peripheral keratinocyte-derived chemokine (KC) in the pathogenesis of neuropathic pain induced by the partial ligation of the sciatic nerve (PLSN) in mice. PLSN increased KC levels and its mRNA in both the sciatic nerve and spinal cord when compared with sham-operated mice. In addition, PLSN-induced mechanical and thermal hyperalgesia was prevented by systemic (i.v.) treatment with anti-KC antibody either at the time of surgery or on the 4th day after surgery. Also, intrathecal (i.t.) injection of anti-KC antibody prevented mechanical hyperalgesia induced by PLSN when administered at the time of surgery or on the 4th day after surgery. Importantly, the intraneural (i.n.) injection of KC in the mouse sciatic nerve elicited long-lasting mechanical hyperalgesia, which was prevented by the selective CXCR2 antagonist SB225002. The established mechanical hyperalgesia induced by KC was expressively reduced by the treatment with gabapentin, a drug widely used to treat chronic pain in humans. Intraneural KC injection also caused neutrophil migration into the mouse sciatic nerve and the depletion of neutrophils, by pre-treating animals with vinblastine, significantly reduced KC-induced mechanical hyperalgesia. Similar results were obtained for the pre-treatment with indomethacin, a non-selective COX inhibitor. We also demonstrated an increased level of cytokines (IL-1β, IL-6, and MCP-1, but not TNF-α) after i.n. injection of KC in the mouse sciatic nerve. Together, these findings suggest a role for KC in the development of neuropathic pain in mice by attracting neutrophils to the injured site and increasing the production of proinflammatory mediators. Therefore, strategies to inhibit the action or the release of this chemokine could constitute a therapeutic tool for the management of neuropathic pain in humans.
authors.affiliation: Department of Pharmacology, Centre of Biological Sciences, Universidade Federal de Santa Catarina, Florianópolis, Brazil.
authors.forename: Marianne Neves
authors.initials: MN
authors.lastname: Manjavachi
authors.affiliation: Department of Pharmacology, Centre of Biological Sciences, Universidade Federal de Santa Catarina, Florianópolis, Brazil.
authors.forename: Robson
authors.initials: R
authors.lastname: Costa
authors.affiliation: Department of Pharmacology, Centre of Biological Sciences, Universidade Federal de Santa Catarina, Florianópolis, Brazil.
authors.forename: Nara Lins
authors.initials: NL
authors.lastname: Quintão
authors.affiliation: Department of Pharmacology, Centre of Biological Sciences, Universidade Federal de Santa Catarina, Florianópolis, Brazil. Electronic address: calixto@farmaco.ufsc.br.
authors.forename: João B
authors.initials: JB
authors.lastname: Calixto
mesh_terms: D000588:Amines / Q000627:therapeutic use; D000700:Analgesics / Q000627:therapeutic use; D000818:Animals; D000906:Antibodies / Q000627:therapeutic use; D018925:Chemokines / Q000276:immunology / Q000378:metabolism*; D003509:Cyclohexanecarboxylic Acids / Q000627:therapeutic use; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D000077206:Gabapentin; D006358:Hot Temperature; D006930:Hyperalgesia / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism*; D007155:Immunologic Factors / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D051379:Mice; D009437:Neuralgia / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism*; D059348:Peripheral Nerve Injuries / Q000150:complications / Q000188:drug therapy / Q000378:metabolism*; D010671:Phenylurea Compounds / Q000494:pharmacology; D023063:Receptors, Interleukin-8B / Q000037:antagonists & inhibitors / Q000378:metabolism; D012584:Sciatic Nerve / Q000187:drug effects / Q000293:injuries* / Q000378:metabolism; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism; D014110:Touch; D014747:Vinblastine / Q000627:therapeutic use; D005680:gamma-Aminobutyric Acid / Q000627:therapeutic use
chemical_list: D000588:Amines; D000700:Analgesics; D000906:Antibodies; D018925:Chemokines; D003509:Cyclohexanecarboxylic Acids; D016861:Cyclooxygenase Inhibitors; D016207:Cytokines; D007155:Immunologic Factors; D010671:Phenylurea Compounds; D023063:Receptors, Interleukin-8B; C112019:SB 225002; C074302:keratinocyte-derived chemokines; D005680:gamma-Aminobutyric Acid; D014747:Vinblastine; D000077206:Gabapentin; D007213:Indomethacin
keywords: Anti-KC antibody; Chronic pain; KC; Keratinocyte-derived chemokine; Neuropathic pain