Efficacy of Chronic Morphine in a Rat Model of Cancer-Induced Bone Pain: Behavior and in Dorsal Horn Pathophysiology
Morphine is one of the main analgesics in cancer-induced bone pain (CIBP). To investigate the efficacy of morphine in CIBP and alteration in dorsal horn pathophysiology, systemic morphine was administered (3 mg/kg) bi-daily between days 11 and 15 after MRMT-1 carcinoma cell injections (compared with...
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| creator | Urch, Catherine E. Donovan-Rodriguez, Tansy Gordon-Williams, Richard Bee, Lucy A. Dickenson, Anthony H. |
| description | Morphine is one of the main analgesics in cancer-induced bone pain (CIBP). To investigate the efficacy of morphine in CIBP and alteration in dorsal horn pathophysiology, systemic morphine was administered (3 mg/kg) bi-daily between days 11 and 15 after MRMT-1 carcinoma cell injections (compared with a single injection (3 mg/kg) of morphine on day 15, and acute spinal morphine (0.1, 1, 10 μg/50 μL). The chronic systemic morphine schedule significantly attenuated pain behavior (von Frey 15 g;
P < .01) to a greater extent than acute systemic morphine (von Frey 15 g;
P < .05). In vivo electrophysiology (day 15 chronic systemic morphine) showed an attenuation of hyperexcitable wide dynamic range (WDR) neurons, but the abnormal raised WDR to nociceptive specific neuronal ratio remained. Acute spinal morphine attenuated electrical and natural WDR neuronal response in shams at a lower dose (1 μg) compared with cancer (10 μg). Chronic morphine is more effective at attenuating pain-related behaviors than single doses, although the dorsal horn retains a pathophysiologic characterization.
This study confirms the resemblance of the rat model to human CIBP with respect to the efficacy of morphine and further suggests that adjuvant therapy is required to reverse the dorsal horn pathophysiology. |
| doi_str_mv | 10.1016/j.jpain.2005.08.005 |
| format | Article |
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P < .01) to a greater extent than acute systemic morphine (von Frey 15 g;
P < .05). In vivo electrophysiology (day 15 chronic systemic morphine) showed an attenuation of hyperexcitable wide dynamic range (WDR) neurons, but the abnormal raised WDR to nociceptive specific neuronal ratio remained. Acute spinal morphine attenuated electrical and natural WDR neuronal response in shams at a lower dose (1 μg) compared with cancer (10 μg). Chronic morphine is more effective at attenuating pain-related behaviors than single doses, although the dorsal horn retains a pathophysiologic characterization.
This study confirms the resemblance of the rat model to human CIBP with respect to the efficacy of morphine and further suggests that adjuvant therapy is required to reverse the dorsal horn pathophysiology.</description><identifier>ISSN: 1526-5900</identifier><identifier>EISSN: 1528-8447</identifier><identifier>DOI: 10.1016/j.jpain.2005.08.005</identifier><identifier>PMID: 16326372</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Action Potentials - drug effects ; Action Potentials - physiology ; Analgesics, Opioid - administration & dosage ; Anesthesia, Intravenous ; Animals ; Behavior, Animal - drug effects ; Behavior, Animal - physiology ; Bone Neoplasms - complications ; Bone Neoplasms - secondary ; Cancer ; Disease Models, Animal ; dorsal horn ; Dose-Response Relationship, Drug ; Drug Administration Schedule ; Injections, Spinal ; Male ; Mammary Neoplasms, Experimental - complications ; Mammary Neoplasms, Experimental - secondary ; morphine ; Morphine - administration & dosage ; Nociceptors - drug effects ; Nociceptors - physiopathology ; pain ; Pain Measurement ; Pain Threshold - drug effects ; Pain Threshold - physiology ; Pain, Intractable - drug therapy ; Pain, Intractable - etiology ; Pain, Intractable - physiopathology ; Physical Stimulation ; Posterior Horn Cells - drug effects ; Posterior Horn Cells - physiopathology ; Rats ; Rats, Sprague-Dawley ; Treatment Outcome ; Tumor Cells, Cultured - transplantation</subject><ispartof>The journal of pain, 2005-12, Vol.6 (12), p.837-845</ispartof><rights>2005 American Pain Society</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c402t-cfde52e1a6fdf11c1fa07c02c30ba8fdb570a22886395d630801810e3c1677db3</citedby><cites>FETCH-LOGICAL-c402t-cfde52e1a6fdf11c1fa07c02c30ba8fdb570a22886395d630801810e3c1677db3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S1526590005008321$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3536,27903,27904,65309</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16326372$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Urch, Catherine E.</creatorcontrib><creatorcontrib>Donovan-Rodriguez, Tansy</creatorcontrib><creatorcontrib>Gordon-Williams, Richard</creatorcontrib><creatorcontrib>Bee, Lucy A.</creatorcontrib><creatorcontrib>Dickenson, Anthony H.</creatorcontrib><title>Efficacy of Chronic Morphine in a Rat Model of Cancer-Induced Bone Pain: Behavior and in Dorsal Horn Pathophysiology</title><title>The journal of pain</title><addtitle>J Pain</addtitle><description>Morphine is one of the main analgesics in cancer-induced bone pain (CIBP). To investigate the efficacy of morphine in CIBP and alteration in dorsal horn pathophysiology, systemic morphine was administered (3 mg/kg) bi-daily between days 11 and 15 after MRMT-1 carcinoma cell injections (compared with a single injection (3 mg/kg) of morphine on day 15, and acute spinal morphine (0.1, 1, 10 μg/50 μL). The chronic systemic morphine schedule significantly attenuated pain behavior (von Frey 15 g;
P < .01) to a greater extent than acute systemic morphine (von Frey 15 g;
P < .05). In vivo electrophysiology (day 15 chronic systemic morphine) showed an attenuation of hyperexcitable wide dynamic range (WDR) neurons, but the abnormal raised WDR to nociceptive specific neuronal ratio remained. Acute spinal morphine attenuated electrical and natural WDR neuronal response in shams at a lower dose (1 μg) compared with cancer (10 μg). Chronic morphine is more effective at attenuating pain-related behaviors than single doses, although the dorsal horn retains a pathophysiologic characterization.
This study confirms the resemblance of the rat model to human CIBP with respect to the efficacy of morphine and further suggests that adjuvant therapy is required to reverse the dorsal horn pathophysiology.</description><subject>Action Potentials - drug effects</subject><subject>Action Potentials - physiology</subject><subject>Analgesics, Opioid - administration & dosage</subject><subject>Anesthesia, Intravenous</subject><subject>Animals</subject><subject>Behavior, Animal - drug effects</subject><subject>Behavior, Animal - physiology</subject><subject>Bone Neoplasms - complications</subject><subject>Bone Neoplasms - secondary</subject><subject>Cancer</subject><subject>Disease Models, Animal</subject><subject>dorsal horn</subject><subject>Dose-Response Relationship, Drug</subject><subject>Drug Administration Schedule</subject><subject>Injections, Spinal</subject><subject>Male</subject><subject>Mammary Neoplasms, Experimental - complications</subject><subject>Mammary Neoplasms, Experimental - secondary</subject><subject>morphine</subject><subject>Morphine - administration & dosage</subject><subject>Nociceptors - drug effects</subject><subject>Nociceptors - physiopathology</subject><subject>pain</subject><subject>Pain Measurement</subject><subject>Pain Threshold - drug effects</subject><subject>Pain Threshold - physiology</subject><subject>Pain, Intractable - drug therapy</subject><subject>Pain, Intractable - etiology</subject><subject>Pain, Intractable - physiopathology</subject><subject>Physical Stimulation</subject><subject>Posterior Horn Cells - drug effects</subject><subject>Posterior Horn Cells - physiopathology</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Treatment Outcome</subject><subject>Tumor Cells, Cultured - transplantation</subject><issn>1526-5900</issn><issn>1528-8447</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kF1LHDEUhkOpqLX-gkLJVe9mPMnsZKLgRd1aFRSltNchm5x0sswm02RW2H_f7Ad459UbwvOenDyEfGFQM2DiYlkvR-1DzQHaGmRd4gM5ZS2XlZzNuo-7s6jaS4AT8innJQBjbdcdkxMmGi6ajp-S6dY5b7TZ0OjovE8xeEOfYhp7H5D6QDX9padyY3HYIToYTNVDsGuDlt7EQr2ULa7oDfb61cdEdbDb4o-Ysh7ofUyhEFMfx36TfRzi381ncuT0kPH8kGfkz8_b3_P76vH57mH-_bEyM-BTZZzFliPTwlnHmGFOQ2eAmwYWWjq7aDvQnEspmsvWigYkMMkAG8NE19lFc0a-7eeOKf5bY57UymeDw6ADxnVWYl_lBWz2oEkx54ROjcmvdNooBmorWy3VTrbaylYgVYnS-noYv16s0L51DnYLcL0HsHzy1WNS2XgsAq1PaCZlo3_3gf-MN5ED</recordid><startdate>20051201</startdate><enddate>20051201</enddate><creator>Urch, Catherine E.</creator><creator>Donovan-Rodriguez, Tansy</creator><creator>Gordon-Williams, Richard</creator><creator>Bee, Lucy A.</creator><creator>Dickenson, Anthony H.</creator><general>Elsevier Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20051201</creationdate><title>Efficacy of Chronic Morphine in a Rat Model of Cancer-Induced Bone Pain: Behavior and in Dorsal Horn Pathophysiology</title><author>Urch, Catherine E. ; Donovan-Rodriguez, Tansy ; Gordon-Williams, Richard ; Bee, Lucy A. ; Dickenson, Anthony H.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c402t-cfde52e1a6fdf11c1fa07c02c30ba8fdb570a22886395d630801810e3c1677db3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Action Potentials - drug effects</topic><topic>Action Potentials - physiology</topic><topic>Analgesics, Opioid - administration & dosage</topic><topic>Anesthesia, Intravenous</topic><topic>Animals</topic><topic>Behavior, Animal - drug effects</topic><topic>Behavior, Animal - physiology</topic><topic>Bone Neoplasms - complications</topic><topic>Bone Neoplasms - secondary</topic><topic>Cancer</topic><topic>Disease Models, Animal</topic><topic>dorsal horn</topic><topic>Dose-Response Relationship, Drug</topic><topic>Drug Administration Schedule</topic><topic>Injections, Spinal</topic><topic>Male</topic><topic>Mammary Neoplasms, Experimental - complications</topic><topic>Mammary Neoplasms, Experimental - secondary</topic><topic>morphine</topic><topic>Morphine - administration & dosage</topic><topic>Nociceptors - drug effects</topic><topic>Nociceptors - physiopathology</topic><topic>pain</topic><topic>Pain Measurement</topic><topic>Pain Threshold - drug effects</topic><topic>Pain Threshold - physiology</topic><topic>Pain, Intractable - drug therapy</topic><topic>Pain, Intractable - etiology</topic><topic>Pain, Intractable - physiopathology</topic><topic>Physical Stimulation</topic><topic>Posterior Horn Cells - drug effects</topic><topic>Posterior Horn Cells - physiopathology</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Treatment Outcome</topic><topic>Tumor Cells, Cultured - transplantation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Urch, Catherine E.</creatorcontrib><creatorcontrib>Donovan-Rodriguez, Tansy</creatorcontrib><creatorcontrib>Gordon-Williams, Richard</creatorcontrib><creatorcontrib>Bee, Lucy A.</creatorcontrib><creatorcontrib>Dickenson, Anthony H.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>The journal of pain</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Urch, Catherine E.</au><au>Donovan-Rodriguez, Tansy</au><au>Gordon-Williams, Richard</au><au>Bee, Lucy A.</au><au>Dickenson, Anthony H.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Efficacy of Chronic Morphine in a Rat Model of Cancer-Induced Bone Pain: Behavior and in Dorsal Horn Pathophysiology</atitle><jtitle>The journal of pain</jtitle><addtitle>J Pain</addtitle><date>2005-12-01</date><risdate>2005</risdate><volume>6</volume><issue>12</issue><spage>837</spage><epage>845</epage><pages>837-845</pages><issn>1526-5900</issn><eissn>1528-8447</eissn><abstract>Morphine is one of the main analgesics in cancer-induced bone pain (CIBP). To investigate the efficacy of morphine in CIBP and alteration in dorsal horn pathophysiology, systemic morphine was administered (3 mg/kg) bi-daily between days 11 and 15 after MRMT-1 carcinoma cell injections (compared with a single injection (3 mg/kg) of morphine on day 15, and acute spinal morphine (0.1, 1, 10 μg/50 μL). The chronic systemic morphine schedule significantly attenuated pain behavior (von Frey 15 g;
P < .01) to a greater extent than acute systemic morphine (von Frey 15 g;
P < .05). In vivo electrophysiology (day 15 chronic systemic morphine) showed an attenuation of hyperexcitable wide dynamic range (WDR) neurons, but the abnormal raised WDR to nociceptive specific neuronal ratio remained. Acute spinal morphine attenuated electrical and natural WDR neuronal response in shams at a lower dose (1 μg) compared with cancer (10 μg). Chronic morphine is more effective at attenuating pain-related behaviors than single doses, although the dorsal horn retains a pathophysiologic characterization.
This study confirms the resemblance of the rat model to human CIBP with respect to the efficacy of morphine and further suggests that adjuvant therapy is required to reverse the dorsal horn pathophysiology.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>16326372</pmid><doi>10.1016/j.jpain.2005.08.005</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Action Potentials - drug effects Action Potentials - physiology Analgesics, Opioid - administration & dosage Anesthesia, Intravenous Animals Behavior, Animal - drug effects Behavior, Animal - physiology Bone Neoplasms - complications Bone Neoplasms - secondary Cancer Disease Models, Animal dorsal horn Dose-Response Relationship, Drug Drug Administration Schedule Injections, Spinal Male Mammary Neoplasms, Experimental - complications Mammary Neoplasms, Experimental - secondary morphine Morphine - administration & dosage Nociceptors - drug effects Nociceptors - physiopathology pain Pain Measurement Pain Threshold - drug effects Pain Threshold - physiology Pain, Intractable - drug therapy Pain, Intractable - etiology Pain, Intractable - physiopathology Physical Stimulation Posterior Horn Cells - drug effects Posterior Horn Cells - physiopathology Rats Rats, Sprague-Dawley Treatment Outcome Tumor Cells, Cultured - transplantation |
| title | Efficacy of Chronic Morphine in a Rat Model of Cancer-Induced Bone Pain: Behavior and in Dorsal Horn Pathophysiology |
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