{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T01:49:59Z","timestamp":1780451399271,"version":"3.54.1"},"reference-count":39,"publisher":"Walter de Gruyter GmbH","issue":"3","license":[{"start":{"date-parts":[[2013,7,1]],"date-time":"2013-07-01T00:00:00Z","timestamp":1372636800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec id=\"j_j.sjpain.2013.05.004_s_001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      There are a number of false myths about buprenorphine based on unconfirmed animal data, even from isolated animal organs, and early clinical research. These myths came into textbooks on pharmacology and pain about 30 years ago and have been difficult to eradicate. Animal models of pain and pain relief are notoriously unreliable as predictors of human clinical effects. The fact is that in clinical practice there is NO bell-shaped dose-response curve, there is NO plateau on the dose-response curve, and there is NO antagonist effect from buprenorphine on other\n                      <jats:italic>mu<\/jats:italic>\n                      -opioid agonists.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_j.sjpain.2013.05.004_s_002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This narrative, topical review of relevant research publications evaluates new knowledge on the pharmacodynamics and pharmacokinetics of buprenorphine of importance in clinical practice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_j.sjpain.2013.05.004_s_003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Buprenorphine is a potent opioid analgesic acting on all four opioid receptors: it is an\n                      <jats:italic>agonist<\/jats:italic>\n                      on the\n                      <jats:italic>mu<\/jats:italic>\n                      -, the\n                      <jats:italic>delta<\/jats:italic>\n                      , and the\n                      <jats:italic>ORL-1<\/jats:italic>\n                      receptors. It is an\n                      <jats:italic>antagonist<\/jats:italic>\n                      at the\n                      <jats:italic>kappa<\/jats:italic>\n                      -receptor. Buprenorphine has a number of active metabolites with different effects on the four opioid receptors; all except the norbup-3-glu are analgesic. Buprenorphine itself is not a respiratory depressant or sedative, but some of its active metabolites are. Buprenorphine and its active metabolites are not excreted by the kidney. Therefore buprenorphine may be used in patients with advanced renal failure.\n                    <\/jats:p>\n                    <jats:p>\n                      Buprenorphine has a slow onset and a long offset. These properties are advantageous, except sometimes when treating severe acute pain. Its agonist effect on the\n                      <jats:italic>ORL-1<\/jats:italic>\n                      receptor reduces reward-effects and slows the development of tolerance to the analgesic effects.\n                    <\/jats:p>\n                    <jats:p>\n                      Buprenorphine inhibits voltage-gated sodium-channels and enhances and prolongs peripheral nerve blocks. Its\n                      <jats:italic>ORL-1<\/jats:italic>\n                      -effect at the spinal cord may do the same.\n                    <\/jats:p>\n                    <jats:p>Buprenorphine is well suited for treatment of chronic pain, especially chronic neuropathic pain and cancer pain. The beneficial effects as a co-medication during treatment of the opioid-abuse disease are due to its slow onset (less \u201ckick-effect\u201d). Its prolonged offset-time reduces the likelihood of acute withdrawal problems and reduces the \u201ccraving\u201d of opioids.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_j.sjpain.2013.05.004_s_004\">\n                    <jats:title>Adverse effects<\/jats:title>\n                    <jats:p>\n                      Buprenorphine, being a\n                      <jats:italic>mu<\/jats:italic>\n                      -agonist, may induce or maintain opioid addiction. Illegally obtained high-dose transmucosal buprenorphine, intended for treatment of addiction, is dissolved and injected by opioid abusers. This is an increasing problem in some countries.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_j.sjpain.2013.05.004_s_005\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Buprenorphine\u2019s unusual pharmacodynamics and pharmacokinetics make it an ideal opioid for treatment of most chronic pain conditions where opioid therapy is indicated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_j.sjpain.2013.05.004_s_006\">\n                    <jats:title>Implications<\/jats:title>\n                    <jats:p>Buprenorphine is a well studied and often misunderstood analgesic opioid drug. The evidence base predicts that it will be an increasingly important alternative for treatment of chronic pain conditions caused by cancer and non-cancer diseases. It will continue to be an attractive alternative to methadone for opioid abuse rehabilitation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1016\/j.sjpain.2013.05.004","type":"journal-article","created":{"date-parts":[[2013,6,3]],"date-time":"2013-06-03T20:32:21Z","timestamp":1370291541000},"page":"148-152","source":"Crossref","is-referenced-by-count":37,"title":["Buprenorphine\u2014Clinically useful but often misunderstood"],"prefix":"10.1515","volume":"4","author":[{"given":"Stephen","family":"Butler","sequence":"first","affiliation":[{"name":"Pain Clinic , Uppsala University Hospital , Uppsala , Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","published-online":{"date-parts":[[2013,7,1]]},"reference":[{"key":"2025120909565754530_j_j.sjpain.2013.05.004_ref_001","doi-asserted-by":"crossref","unstructured":"Dum J, Herz A. Invivo receptorbinding of the opiate partial agonist, buprenorphine, correlated with its agonistic and antagonistic actions. 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