{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T12:08:22Z","timestamp":1785413302761,"version":"3.56.0"},"posted":{"date-parts":[[2026,5,6]]},"group-title":"Pharmacology and Toxicology","reference-count":50,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T00:00:00Z","timestamp":1778025600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"award":["R37-DA33397"],"award-info":[{"award-number":["R37-DA33397"]}],"id":[{"id":"https:\/\/ror.org\/00fq5cm18","id-type":"ROR","asserted-by":"publisher"}]},{"award":["T32-TR004764"],"award-info":[{"award-number":["T32-TR004764"]}],"id":[{"id":"https:\/\/ror.org\/04pw6fb54","id-type":"ROR","asserted-by":"publisher"}]},{"award":["CDMRP W81XWH-21-1-0071"],"award-info":[{"award-number":["CDMRP W81XWH-21-1-0071"]}],"id":[{"id":"https:\/\/ror.org\/0447fe631","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,5,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Neuropathic pain is a major source of disability and distress with few pharmacological options for treatment. Opioid drugs can be effective, but high doses are needed, leading to unwanted effects. BMS-986122 is a positive allosteric modulator of the mu opioid receptor that potentiates acute opioid antinociception without increasing opioid-induced constipation, reward, or respiratory depression. Therefore, we asked if BMS-986122 could increase the effects of low-dose opioid analgesics in chronic neuropathic pain.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We employed the spared nerve injury and tibial neuroma models in rats and assessed the tactile hypersensitivity of the hind paw and site of neuroma, respectively.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Administration of low doses of (R)-methadone, morphine, or buprenorphine slightly reduced the tactile hypersensitivity of the hind paw the in spared nerve injury model. Pretreatment with BMS-986122 significantly enhanced the reversal of hypersensitivity, reaching the effect of high-dose gabapentin, a standard of care in neuropathic pain. Pretreatment with BMS-986122 similarly increased the anti-allodynic effects of low dose (R)-methadone on neuroma pain. A similar effect of (R)-methadone in the absence of BMS-986122 was only observed at a dose where respiratory distress was seen.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>These findings show that allosteric modulators of the mu opioid receptor such as BMS-986122 can enhance opioid activity that could translate to a safe and effective treatment for chronic neuropathic pain.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.05.03.722511","type":"posted-content","created":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T04:55:16Z","timestamp":1778129716000},"source":"Crossref","is-referenced-by-count":0,"title":["Effects of the Mu Opioid Receptor Positive Allosteric Modulator BMS-986122 On Opioid Efficacy in Rat Neuropathic Pain States"],"prefix":"10.64898","author":[{"given":"Benjamin M.","family":"Clements","sequence":"first","affiliation":[{"name":"Department of Pharmacology, University of Michigan Medical School; Ann Arbor, Michigan 48103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ipek","family":"Berberoglu","sequence":"additional","affiliation":[{"name":"Department of Plastic Surgery, University of Michigan Medical School; Ann Arbor, Michigan 48103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine L.","family":"Burke","sequence":"additional","affiliation":[{"name":"Department of Plastic Surgery, University of Michigan Medical School; Ann Arbor, Michigan 48103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen W.P.","family":"Kemp","sequence":"additional","affiliation":[{"name":"Department of Plastic Surgery, University of Michigan Medical School; Ann Arbor, Michigan 48103, USA"},{"name":"Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan 48103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John R.","family":"Traynor","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Michigan Medical School; Ann Arbor, Michigan 48103, USA"},{"name":"Department of Medicinal Chemistry, University of Michigan School of Pharmacy; Ann Arbor, Michigan 48103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026050916552507000_2026.05.03.722511v1.1","doi-asserted-by":"crossref","first-page":"2082","DOI":"10.1016\/S0140-6736(21)00393-7","article-title":"Chronic pain: an update on burden, best practices, and new advances","volume":"397","year":"2021","journal-title":"The Lancet"},{"key":"2026050916552507000_2026.05.03.722511v1.2","doi-asserted-by":"crossref","unstructured":"Baldini A , Von Korff M , Lin EH : A Review of Potential Adverse Effects of Long-Term Opioid Therapy: A Practitioner\u2019s Guide. 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