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Macrophages in dorsal root ganglia (DRGs) are involved in the enhanced regeneration that occurs after a conditioning lesion (CL), but how macrophages stimulate this response is not known. Oncomodulin (Ocm) has been proposed as a proregenerative molecule secreted by macrophages and neutrophils, is expressed in the DRG after axotomy, and stimulates neurite outgrowth by DRG neurons in culture. Wild-type (WT) and<jats:italic>Ocm<\/jats:italic>knock-out (KO) mice were used to investigate whether Ocm plays a role in the CL response in DRG neurons after sciatic nerve transection. Neurite outgrowth was measured after 24 and 48 h in explant culture 7 d after a CL. Sciatic nerve regeneration was also measured<jats:italic>in vivo<\/jats:italic>7 d after a CL and 2 d after a subsequent sciatic nerve crush. The magnitude of the increased neurite outgrowth following a CL was significantly smaller in explants from<jats:italic>Ocm<\/jats:italic>KO mice than in explants from WT mice.<jats:italic>In vivo<\/jats:italic>after a CL, increased regeneration was found in WT animals but not in KO animals. Macrophage accumulation and levels of<jats:italic>interleukin-6<\/jats:italic>(<jats:italic>IL-6<\/jats:italic>) mRNA were measured in axotomized DRG from WT and<jats:italic>Ocm<\/jats:italic>KO animals, and both were significantly higher than in sham-operated ganglia. At 6 h after axotomy,<jats:italic>Il<\/jats:italic>-6 mRNA was higher in WT than in<jats:italic>Ocm<\/jats:italic>KO mice. Our data support the hypothesis that Ocm plays a necessary role in producing a normal CL response and that its effects possibly result in part from stimulation of the expression of proregenerative macrophage cytokines such as IL-6.<\/jats:p>","DOI":"10.1523\/eneuro.0477-21.2022","type":"journal-article","created":{"date-parts":[[2022,2,7]],"date-time":"2022-02-07T19:15:14Z","timestamp":1644261314000},"page":"ENEURO.0477-21.2022","source":"Crossref","is-referenced-by-count":12,"title":["The Conditioning Lesion Response in Dorsal Root Ganglion Neurons Is Inhibited in Oncomodulin Knock-Out Mice"],"prefix":"10.1523","volume":"9","author":[{"given":"Jon 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