Differential effects of repeated low dose treatment with the cannabinoid agonist WIN 55,212-2 in experimental models of bone cancer pain and neuropathic pain
Pain due to bone malignancies is one of the most difficult types of cancer pain to fully control and may further decrease the patients' quality of life. Animal models of chronic pain conditions resulting from peripheral inflammatory reactions or nerve injuries are responsive to treatment with c...
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| Veröffentlicht in: | Pharmacology, biochemistry and behavior biochemistry and behavior, 2008-11, Vol.91 (1), p.38-46 |
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| creator | Hald, Andreas Ding, Ming Egerod, Kristoffer Hansen, Rikke R. Konradsen, Dorthe Jørgensen, Stine G. Atalay, Baris Nasser, Arafat Bjerrum, Ole J. Heegaard, Anne-Marie |
| description | Pain due to bone malignancies is one of the most difficult types of cancer pain to fully control and may further decrease the patients' quality of life. Animal models of chronic pain conditions resulting from peripheral inflammatory reactions or nerve injuries are responsive to treatment with cannabinoid agonists. However, the use of cannabinoid agonists in humans may be hampered by CNS related side effects and development of tolerance. In the present study, we investigated the effect of repeated low dose administration of the synthetic cannabinoid agonist WIN 55,212-2 on bone cancer pain and neuropathic pain in mice. In addition, we investigated the development of CNS related side effects and tolerance. We found that 0.5 mg/kg/day for 18 days reduced pain related behavior and expression of spinal glial fibrillary acidic protein in the bone cancer pain model but not in the neuropathic pain model. Furthermore, this treatment strategy was not found to induce measurable CNS related side effects or tolerance. Cancer cell viability assays and bone volume fraction assessed by micro computed tomography (μCT) demonstrated that these effects were not due to changes in cancer progression. The difference in WIN 55,212-2 efficacy between the bone cancer and neuropathic pain models may reflect the different pain generating mechanisms, which may be utilized in designing new therapeutic drugs. |
| doi_str_mv | 10.1016/j.pbb.2008.04.021 |
| format | Article |
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Animal models of chronic pain conditions resulting from peripheral inflammatory reactions or nerve injuries are responsive to treatment with cannabinoid agonists. However, the use of cannabinoid agonists in humans may be hampered by CNS related side effects and development of tolerance. In the present study, we investigated the effect of repeated low dose administration of the synthetic cannabinoid agonist WIN 55,212-2 on bone cancer pain and neuropathic pain in mice. In addition, we investigated the development of CNS related side effects and tolerance. We found that 0.5 mg/kg/day for 18 days reduced pain related behavior and expression of spinal glial fibrillary acidic protein in the bone cancer pain model but not in the neuropathic pain model. Furthermore, this treatment strategy was not found to induce measurable CNS related side effects or tolerance. Cancer cell viability assays and bone volume fraction assessed by micro computed tomography (μCT) demonstrated that these effects were not due to changes in cancer progression. The difference in WIN 55,212-2 efficacy between the bone cancer and neuropathic pain models may reflect the different pain generating mechanisms, which may be utilized in designing new therapeutic drugs.</description><identifier>ISSN: 0091-3057</identifier><identifier>EISSN: 1873-5177</identifier><identifier>DOI: 10.1016/j.pbb.2008.04.021</identifier><identifier>PMID: 18611408</identifier><identifier>CODEN: PBBHAU</identifier><language>eng</language><publisher>New York, NY: Elsevier Inc</publisher><subject>Analgesics - therapeutic use ; Animals ; Benzoxazines - therapeutic use ; Biological and medical sciences ; Bone ; Bone Neoplasms - complications ; Cancer ; Cannabinoid ; Cannabinoid Receptor Agonists ; Cell Line ; Cranial nerves. Spinal roots. Peripheral nerves. Autonomic nervous system. Gustation. 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Animal models of chronic pain conditions resulting from peripheral inflammatory reactions or nerve injuries are responsive to treatment with cannabinoid agonists. However, the use of cannabinoid agonists in humans may be hampered by CNS related side effects and development of tolerance. In the present study, we investigated the effect of repeated low dose administration of the synthetic cannabinoid agonist WIN 55,212-2 on bone cancer pain and neuropathic pain in mice. In addition, we investigated the development of CNS related side effects and tolerance. We found that 0.5 mg/kg/day for 18 days reduced pain related behavior and expression of spinal glial fibrillary acidic protein in the bone cancer pain model but not in the neuropathic pain model. Furthermore, this treatment strategy was not found to induce measurable CNS related side effects or tolerance. Cancer cell viability assays and bone volume fraction assessed by micro computed tomography (μCT) demonstrated that these effects were not due to changes in cancer progression. The difference in WIN 55,212-2 efficacy between the bone cancer and neuropathic pain models may reflect the different pain generating mechanisms, which may be utilized in designing new therapeutic drugs.</description><subject>Analgesics - therapeutic use</subject><subject>Animals</subject><subject>Benzoxazines - therapeutic use</subject><subject>Biological and medical sciences</subject><subject>Bone</subject><subject>Bone Neoplasms - complications</subject><subject>Cancer</subject><subject>Cannabinoid</subject><subject>Cannabinoid Receptor Agonists</subject><subject>Cell Line</subject><subject>Cranial nerves. Spinal roots. Peripheral nerves. Autonomic nervous system. Gustation. Olfaction</subject><subject>Dose-Response Relationship, Drug</subject><subject>Drug Tolerance</subject><subject>Ganglia, Spinal - physiology</subject><subject>Glial Fibrillary Acidic Protein - biosynthesis</subject><subject>Immunohistochemistry</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Inbred C3H</subject><subject>Morpholines - therapeutic use</subject><subject>Motor Activity - drug effects</subject><subject>Naphthalenes - therapeutic use</subject><subject>Nervous system (semeiology, syndromes)</subject><subject>Neurology</subject><subject>Pain</subject><subject>Pain - drug therapy</subject><subject>Pain - etiology</subject><subject>Pain Measurement - drug effects</subject><subject>Peripheral Nervous System Diseases - complications</subject><subject>Physical Stimulation</subject><subject>Postural Balance - drug effects</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>RNA - biosynthesis</subject><subject>RNA - isolation & purification</subject><subject>Tomography, X-Ray Computed</subject><subject>Weight-Bearing - physiology</subject><subject>WIN 55,212-2</subject><issn>0091-3057</issn><issn>1873-5177</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kc2O1DAQhCMEYoeFB-CCfIETGdqOEzvitFr-VlrBBcTR6jgdxqOMHWwPCw_Du-L5Edw42Wp9VW5XVdVTDmsOvHu1XS_DsBYAeg1yDYLfq1Zcq6ZuuVL3qxVAz-sGWnVRPUppCwBSdOphdcF1x7kEvap-v3HTRJF8djgzKnebEwsTi7QQZhrZHO7YGBKxHMtgV0h25_KG5Q0xi97j4HxwI8NvwbuU2debj6xtXwouasGcZ_RzoegOuvLALow0H_2H4I96S5EtWDj0I_O0j2HBvHH2OHxcPZhwTvTkfF5WX969_Xz9ob799P7m-uq2tpKLXEvqRN8gWT1iD52QCNj2Qk0wWY2dFi3qRvayITkMXKBsRIet6nXfSSmsbS6rFyffJYbve0rZ7FyyNM_oKeyTEdCrRvRtAfkJtDGkFGkyS_kbxl-Ggzl0YramdGIOnRiQpnRSNM_O5vthR-M_xbmEAjw_A5gszlMsqbj0lxPQKd0qUbjXJ65ESD8cRZOso5Lg6GKpzYzB_WeNP7t4qdA</recordid><startdate>20081101</startdate><enddate>20081101</enddate><creator>Hald, Andreas</creator><creator>Ding, Ming</creator><creator>Egerod, Kristoffer</creator><creator>Hansen, Rikke R.</creator><creator>Konradsen, Dorthe</creator><creator>Jørgensen, Stine G.</creator><creator>Atalay, Baris</creator><creator>Nasser, Arafat</creator><creator>Bjerrum, Ole J.</creator><creator>Heegaard, Anne-Marie</creator><general>Elsevier Inc</general><general>Elsevier Science</general><scope>IQODW</scope><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>7QG</scope><scope>7TK</scope></search><sort><creationdate>20081101</creationdate><title>Differential effects of repeated low dose treatment with the cannabinoid agonist WIN 55,212-2 in experimental models of bone cancer pain and neuropathic pain</title><author>Hald, Andreas ; Ding, Ming ; Egerod, Kristoffer ; Hansen, Rikke R. ; Konradsen, Dorthe ; Jørgensen, Stine G. ; Atalay, Baris ; Nasser, Arafat ; Bjerrum, Ole J. ; Heegaard, Anne-Marie</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c412t-4e6293aec8da90624a0a5927f0fc8a6825a834943e4bb12a4326a579896442cc3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Analgesics - therapeutic use</topic><topic>Animals</topic><topic>Benzoxazines - therapeutic use</topic><topic>Biological and medical sciences</topic><topic>Bone</topic><topic>Bone Neoplasms - complications</topic><topic>Cancer</topic><topic>Cannabinoid</topic><topic>Cannabinoid Receptor Agonists</topic><topic>Cell Line</topic><topic>Cranial nerves. Spinal roots. Peripheral nerves. Autonomic nervous system. Gustation. Olfaction</topic><topic>Dose-Response Relationship, Drug</topic><topic>Drug Tolerance</topic><topic>Ganglia, Spinal - physiology</topic><topic>Glial Fibrillary Acidic Protein - biosynthesis</topic><topic>Immunohistochemistry</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Inbred C3H</topic><topic>Morpholines - therapeutic use</topic><topic>Motor Activity - drug effects</topic><topic>Naphthalenes - therapeutic use</topic><topic>Nervous system (semeiology, syndromes)</topic><topic>Neurology</topic><topic>Pain</topic><topic>Pain - drug therapy</topic><topic>Pain - etiology</topic><topic>Pain Measurement - drug effects</topic><topic>Peripheral Nervous System Diseases - complications</topic><topic>Physical Stimulation</topic><topic>Postural Balance - drug effects</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>RNA - biosynthesis</topic><topic>RNA - isolation & purification</topic><topic>Tomography, X-Ray Computed</topic><topic>Weight-Bearing - physiology</topic><topic>WIN 55,212-2</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hald, Andreas</creatorcontrib><creatorcontrib>Ding, Ming</creatorcontrib><creatorcontrib>Egerod, Kristoffer</creatorcontrib><creatorcontrib>Hansen, Rikke R.</creatorcontrib><creatorcontrib>Konradsen, Dorthe</creatorcontrib><creatorcontrib>Jørgensen, Stine G.</creatorcontrib><creatorcontrib>Atalay, Baris</creatorcontrib><creatorcontrib>Nasser, Arafat</creatorcontrib><creatorcontrib>Bjerrum, Ole J.</creatorcontrib><creatorcontrib>Heegaard, Anne-Marie</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Animal Behavior Abstracts</collection><collection>Neurosciences Abstracts</collection><jtitle>Pharmacology, biochemistry and behavior</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hald, Andreas</au><au>Ding, Ming</au><au>Egerod, Kristoffer</au><au>Hansen, Rikke R.</au><au>Konradsen, Dorthe</au><au>Jørgensen, Stine G.</au><au>Atalay, Baris</au><au>Nasser, Arafat</au><au>Bjerrum, Ole J.</au><au>Heegaard, Anne-Marie</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Differential effects of repeated low dose treatment with the cannabinoid agonist WIN 55,212-2 in experimental models of bone cancer pain and neuropathic pain</atitle><jtitle>Pharmacology, biochemistry and behavior</jtitle><addtitle>Pharmacol Biochem Behav</addtitle><date>2008-11-01</date><risdate>2008</risdate><volume>91</volume><issue>1</issue><spage>38</spage><epage>46</epage><pages>38-46</pages><issn>0091-3057</issn><eissn>1873-5177</eissn><coden>PBBHAU</coden><abstract>Pain due to bone malignancies is one of the most difficult types of cancer pain to fully control and may further decrease the patients' quality of life. Animal models of chronic pain conditions resulting from peripheral inflammatory reactions or nerve injuries are responsive to treatment with cannabinoid agonists. However, the use of cannabinoid agonists in humans may be hampered by CNS related side effects and development of tolerance. In the present study, we investigated the effect of repeated low dose administration of the synthetic cannabinoid agonist WIN 55,212-2 on bone cancer pain and neuropathic pain in mice. In addition, we investigated the development of CNS related side effects and tolerance. We found that 0.5 mg/kg/day for 18 days reduced pain related behavior and expression of spinal glial fibrillary acidic protein in the bone cancer pain model but not in the neuropathic pain model. Furthermore, this treatment strategy was not found to induce measurable CNS related side effects or tolerance. Cancer cell viability assays and bone volume fraction assessed by micro computed tomography (μCT) demonstrated that these effects were not due to changes in cancer progression. The difference in WIN 55,212-2 efficacy between the bone cancer and neuropathic pain models may reflect the different pain generating mechanisms, which may be utilized in designing new therapeutic drugs.</abstract><cop>New York, NY</cop><pub>Elsevier Inc</pub><pmid>18611408</pmid><doi>10.1016/j.pbb.2008.04.021</doi><tpages>9</tpages></addata></record> |
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| subjects | Analgesics - therapeutic use Animals Benzoxazines - therapeutic use Biological and medical sciences Bone Bone Neoplasms - complications Cancer Cannabinoid Cannabinoid Receptor Agonists Cell Line Cranial nerves. Spinal roots. Peripheral nerves. Autonomic nervous system. Gustation. Olfaction Dose-Response Relationship, Drug Drug Tolerance Ganglia, Spinal - physiology Glial Fibrillary Acidic Protein - biosynthesis Immunohistochemistry Male Medical sciences Mice Mice, Inbred C3H Morpholines - therapeutic use Motor Activity - drug effects Naphthalenes - therapeutic use Nervous system (semeiology, syndromes) Neurology Pain Pain - drug therapy Pain - etiology Pain Measurement - drug effects Peripheral Nervous System Diseases - complications Physical Stimulation Postural Balance - drug effects Reverse Transcriptase Polymerase Chain Reaction RNA - biosynthesis RNA - isolation & purification Tomography, X-Ray Computed Weight-Bearing - physiology WIN 55,212-2 |
| title | Differential effects of repeated low dose treatment with the cannabinoid agonist WIN 55,212-2 in experimental models of bone cancer pain and neuropathic pain |
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