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K<jats:sub>2p<\/jats:sub>1.1 controls neuronal excitability by setting the resting membrane potential. Here, we report that systemic injection of the chemotherapy agent paclitaxel time\u2010dependently downregulates the expression of <jats:italic>K<\/jats:italic><jats:sub>\n<jats:italic>2p<\/jats:italic><\/jats:sub><jats:italic>1.1<\/jats:italic> mRNA and its coding K<jats:sub>2p<\/jats:sub>1.1 protein in the DRG neurons. Rescuing this downregulation mitigates the development and maintenance of paclitaxel\u2010induced mechanical allodynia and heat hyperalgesia. Conversely, in the absence of paclitaxel administration, mimicking this downregulation decreases outward potassium current and increases excitability in the DRG neurons, leading to the enhanced responses to mechanical and heat stimuli. Mechanically, the downregulation of DRG <jats:italic>K<\/jats:italic><jats:sub>\n<jats:italic>2p<\/jats:italic><\/jats:sub><jats:italic>1.1<\/jats:italic> mRNA is attributed to paclitaxel\u2010induced increase in DRG DNMT3a, as blocking this increase reverses the paclitaxel\u2010induced the decrease of DRG K<jats:sub>2p<\/jats:sub>1.1 and mimicking this increase reduces DRG K<jats:sub>2p<\/jats:sub>1.1 expression. In addition, paclitaxel injection increases the binding of DNMT3a to the <jats:italic>K<\/jats:italic><jats:sub>\n<jats:italic>2p<\/jats:italic><\/jats:sub><jats:italic>1.1<\/jats:italic> gene promoter region and elevates the level of DNA methylation within this region in the DRG. These findings suggest that DNMT3a\u2010triggered downregulation of DRG K<jats:sub>2p<\/jats:sub>1.1 may contribute to chemotherapy\u2010induced neuropathic pain.<\/jats:p>","DOI":"10.1002\/ijc.32155","type":"journal-article","created":{"date-parts":[[2019,1,26]],"date-time":"2019-01-26T16:29:12Z","timestamp":1548520152000},"page":"2122-2134","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":66,"title":["DNMT3a\u2010triggered downregulation of K<sub>2p<\/sub>1.1 gene in primary sensory neurons contributes to paclitaxel\u2010induced neuropathic pain"],"prefix":"10.1002","volume":"145","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9268-4846","authenticated-orcid":false,"given":"Qingxiang","family":"Mao","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, New Jersey Medical School, Rutgers The State University of New Jersey  Newark NJ"},{"name":"Department of Anesthesiology Daping Hospital, Institute of 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