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This randomized, patient-blinded, split-face study evaluated a novel \u201cionization-adjusted\u201d PN filler with modified pH and ionic strength designed to reduce injection pain without compromising efficacy. Fifteen participants received 1\u00a0mL of conventional PN filler on one side of the face and 1 mL of the ionized PN filler on the other. Pain was assessed using a 10-point Visual Analog Scale (VAS), while wrinkle improvement was evaluated using the Crow\u2019s Feet Grading Scale (CFGS) and Global Aesthetic Improvement Scale (GAIS). The ionized PN filler demonstrated significantly lower pain scores (VAS 3.39 \u00b1 1.81) compared to the conventional filler (VAS 5.04 \u00b1 2.19, p &lt; 0.005), with fewer cases of erythema (40% vs. 60%) and embossing (13.3% vs. 56.7%). Both formulations showed significant improvements in CFGS and GAIS scores without statistical differences. These findings suggest that ionization-adjusted PN filler provides a more comfortable injection experience while maintaining similar clinical efficacy and safety profiles.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Level of Evidence I<\/jats:title>\n                    <jats:p>\n                      This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.springer.com\/00266\" ext-link-type=\"uri\">www.springer.com\/00266<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00266-025-05320-x","type":"journal-article","created":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T17:13:38Z","timestamp":1765214018000},"page":"2723-2730","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Efficacy of Ionization-Adjusted PN Filler in Minimizing Injection Pain: A Randomized, Patient-Blinded, Split-Face Study"],"prefix":"10.1007","volume":"50","author":[{"given":"Woosang","family":"Jeon","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minwoo","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sug Won","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1724-4250","authenticated-orcid":false,"given":"Jiye","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,12,8]]},"reference":[{"key":"5320_CR1","doi-asserted-by":"publisher","first-page":"4101","DOI":"10.3390\/ijms25074101","volume":"25","author":"X He","year":"2024","unstructured":"He X, Gao X, Xie W. 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