{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T17:48:46Z","timestamp":1778953726605,"version":"3.51.4"},"reference-count":53,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2022,7,11]],"date-time":"2022-07-11T00:00:00Z","timestamp":1657497600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Deputyship for Research and Innovation, Ministry of Education in Saudi Arabia","award":["375213500"],"award-info":[{"award-number":["375213500"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The current study reports the fabrication of co-combination gel using Pregabalin and Withania coagulans fruit extract to validate its effectiveness for neuropathic pain in chronic constriction injury (CCI) rat models. Three topical gels were prepared using Carbopol 934 through a pseudo-ternary phase diagram incorporating the Pregabalin (2.5%), Withania coagulans extract (2%), and co-combination of both Pregabalin (2.5%) and Withania coagulans extract (2%). Gels were characterized. FTIR showed a successful polymeric network of the gel without any interaction. The drug distribution at the molecular level was confirmed by XRD. The AFM images topographically indicated the rough surface of gels with a size range from 0.25 to 330 nm. DSC showed the disappearance of sharp peaks of the drug and extract, showing successful incorporation into the polymeric network of gels. The in vitro drug release of co-combination gel was 73% over 48 h. The mechanism of drug release by combination gel was Higuchi+ fickian with values of n (0.282) and R2 (0.947). An in vivo study for pain assessment via four methods: (i) heat hyperalgesia, (ii) cold allodynia, (iii) mechano-hyperalgesia, and (iv) dynamic mechano-allodynia, confirmed that topical treatment with co-combination gel reduced the pain significantly as indicated by the p value: R1 (p &lt; 0.001), R2 (p &lt; 0.001), R3 (p &lt; 0.015), and R4 (p &lt; 0.0344). The significance order was R2 (****) &gt; R1 (***) &gt; R3 (**) &gt; R4 (*) &gt; R5 (ns).<\/jats:p>","DOI":"10.3390\/molecules27144433","type":"journal-article","created":{"date-parts":[[2022,7,12]],"date-time":"2022-07-12T03:50:36Z","timestamp":1657597836000},"page":"4433","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Co-Combination of Pregabalin and Withania coagulans-Extract-Loaded Topical Gel Alleviates Allodynia and Hyperalgesia in the Chronic Sciatic Nerve Constriction Injury for Neuropathic Pain in Animal Model"],"prefix":"10.3390","volume":"27","author":[{"given":"Anam","family":"Asghar","sequence":"first","affiliation":[{"name":"Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Government College University Faisalabad, Punjab 38000, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muhammad Naeem","family":"Aamir","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, Faculty of Pharmacy, The Islamia University of Bahawalpur, Bahawalpur 63100, Pakistan"},{"name":"School of Pharmacy, Newcastle University, Newcastle Upon Tyne NE1 7RU, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fatima Akbar","family":"Sheikh","sequence":"additional","affiliation":[{"name":"Al-Raziq College of Pharmacy, Sargodha 40100, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2312-3137","authenticated-orcid":false,"given":"Naveed","family":"Ahmad","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy, Jouf University, Sakaka 72388, Al Jouf, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mervat A.","family":"Elsherif","sequence":"additional","affiliation":[{"name":"Chemistry Department, College of Science, Jouf University, Sakaka 72388, Al Jouf, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8125-7972","authenticated-orcid":false,"given":"Syed Nasir","family":"Abbas Bukhari","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, College of Pharmacy, Jouf University, Sakaka 72388, Al Jouf, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"17002","DOI":"10.1038\/nrdp.2017.2","article-title":"Neuropathic pain","volume":"3","author":"Colloca","year":"2017","journal-title":"Nat. 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