{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T18:45:51Z","timestamp":1781549151921,"version":"3.54.5"},"reference-count":24,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,1,22]],"date-time":"2024-01-22T00:00:00Z","timestamp":1705881600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000923","name":"Australian Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000923","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100020111","name":"Therapeutic Innovation Australia","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100020111","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>There is a large unmet need for novel pain-killers to improve relief of painful diabetic neuropathy (PDN). Herein, we assessed the efficacy of the somatostatin type 4 (SST<jats:sub>4<\/jats:sub>) receptor agonist, J-2156, for relief of PDN in rats. Diabetes was induced with streptozotocin (STZ; 70\u00a0mg\/kg) and bilateral hindpaw hypersensitivity was fully developed by 8-week post-STZ. In the intervals, 8\u201312-weeks (morphine-sensitive phase; Phase 1) and 16\u201318-weeks (morphine-hyposensitive phase; Phase 2) post-STZ, rats received a single dose of intraperitoneal (i.p.) J-2156 (10, 20, 30\u00a0mg\/kg), gabapentin (100\u00a0mg\/kg i.p.), subcutaneous morphine (1\u00a0mg\/kg) or vehicle. Hindpaw withdrawal thresholds (PWTs) were assessed using von Frey filaments pre-dose and at regular intervals over 3-h post-dose. In Phase 1, J-2156\u00a0at 30\u00a0mg\/kg evoked significant anti-allodynia in the hindpaws with maximal effect at 1.5\u00a0h compared with 1\u00a0h for gabapentin and morphine. The durations of action for all three compounds were greater than 3\u00a0h. The corresponding mean (\u00b1SEM) extent and duration of anti-allodynia (\u0394PWT AUC) for gabapentin did not differ significantly from that for J-2156 (30\u00a0mg\/kg) or morphine. However, in Phase 2, the \u0394PWT AUC for morphine was reduced to approximately 25% of that in Phase 1, mirroring our previous work. Similarly, the mean (\u00b1SEM) \u0394PWT AUC for J-2156 (30\u00a0mg\/kg) in Phase 2 was approximately 45% of that for Phase 1 whereas for gabapentin the mean (\u00b1SEM) \u0394PWT AUCs did not differ significantly (<jats:italic>p<\/jats:italic> &amp;gt; 0.05) between the two phases. Our findings further describe the preclinical pain relief profile of J-2156 and complement previous work in rat models of inflammatory pain, neuropathic pain and low back pain. SST<jats:sub>4<\/jats:sub> receptor agonists hold promise as novel therapeutics for the relief of PDN, a type of peripheral neuropathic pain that is often intractable to relief with clinically used drug treatment options.<\/jats:p>","DOI":"10.3389\/fphar.2024.1346801","type":"journal-article","created":{"date-parts":[[2024,1,22]],"date-time":"2024-01-22T04:29:13Z","timestamp":1705897753000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["J-2156, a small molecule somatostatin type 4 receptor agonist, alleviated hindpaw hypersensitivity in the streptozotocin-induced rat model of painful diabetic neuropathy but with a 2-fold decrease in potency at an advanced stage in the model, mimicking morphine"],"prefix":"10.3389","volume":"15","author":[{"given":"A.","family":"Kuo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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