The potential anti-inflammatory and anti-nociceptive effects of rat hemopressin (PVNFKFLSH) in experimental arthritis
Inflammatory arthritis, such as rheumatoid arthritis (RA), stands out as one of the main sources of pain and impairment to the quality of life. The use of hemopressin (PVNFKFLSH; Hp), an inverse agonist of type 1 cannabinoid receptor, has proven to be effective in producing analgesia in pain models,...
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| creator | Camargo, Livia L. Denadai-Souza, Alexandre Yshii, Lidia M. Lima, Carla Teixeira, Simone A. Cerqueira, Anderson R.A. Gewehr, Mayara C.F. Fernandes, Elizabeth S. Schenka, André A. Muscará, Marcelo N. Ferro, Emer S. Costa, Soraia K.P. |
| description | Inflammatory arthritis, such as rheumatoid arthritis (RA), stands out as one of the main sources of pain and impairment to the quality of life. The use of hemopressin (PVNFKFLSH; Hp), an inverse agonist of type 1 cannabinoid receptor, has proven to be effective in producing analgesia in pain models, but its effect on neuro-inflammatory aspects of RA is limited. In this study, antigen-induced arthritis (AIA) was evoked by the intraarticular (i.art.) injection of methylated bovine serum albumin (mBSA) in male Sprague Dawley rats. Phosphate buffered saline (PBS)-injected ipsilateral knee joints or AIA contralateral were used as control. Nociceptive and inflammatory parameters such as knee joint oedema and leukocyte influx and histopathological changes were carried out in addition to the local measurement of interleukins (IL) IL-6, IL-1β, tumor necrosis factor-α and the immunoreactivity of the neuropeptides substance P (SP) and calcitonin gene related peptide (CGRP) in the spinal cord (lumbar L3-5 segments) of AIA rats. For 4 days, AIA rats were treated daily with a single administration of saline, Hp injected (10 or 20 μg/day, i.art.), Hp given orally (20 μg/Kg, p.o.) or indomethacin (Indo; 5 mg/Kg, i.p.). In comparison to the PBS control group, the induction of AIA produced a significant and progressive mono-arthritis condition. The degree of AIA severity progressively compromised the normal walking pattern and impaired mobility over the next four days in relation to PBS-injected rats or contralateral knee joints. In AIA rats, the reduction of the distance between footprints and disturbances of gait evidenced signs of nociception. This response worsened at day 4, and a loss of footprint from the ipsilateral hind paw was evident. Daily treatment of the animals with Hp either i.art. (10 and 20 μg/knee) or p.o. (20 μg/Kg) as well as Indo (5 mg/Kg, i.p.) ameliorated the impaired mobility in a time-dependent manner (P |
| doi_str_mv | 10.1016/j.ejphar.2020.173636 |
| format | Article |
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The use of hemopressin (PVNFKFLSH; Hp), an inverse agonist of type 1 cannabinoid receptor, has proven to be effective in producing analgesia in pain models, but its effect on neuro-inflammatory aspects of RA is limited. In this study, antigen-induced arthritis (AIA) was evoked by the intraarticular (i.art.) injection of methylated bovine serum albumin (mBSA) in male Sprague Dawley rats. Phosphate buffered saline (PBS)-injected ipsilateral knee joints or AIA contralateral were used as control. Nociceptive and inflammatory parameters such as knee joint oedema and leukocyte influx and histopathological changes were carried out in addition to the local measurement of interleukins (IL) IL-6, IL-1β, tumor necrosis factor-α and the immunoreactivity of the neuropeptides substance P (SP) and calcitonin gene related peptide (CGRP) in the spinal cord (lumbar L3-5 segments) of AIA rats. For 4 days, AIA rats were treated daily with a single administration of saline, Hp injected (10 or 20 μg/day, i.art.), Hp given orally (20 μg/Kg, p.o.) or indomethacin (Indo; 5 mg/Kg, i.p.). In comparison to the PBS control group, the induction of AIA produced a significant and progressive mono-arthritis condition. The degree of AIA severity progressively compromised the normal walking pattern and impaired mobility over the next four days in relation to PBS-injected rats or contralateral knee joints. In AIA rats, the reduction of the distance between footprints and disturbances of gait evidenced signs of nociception. This response worsened at day 4, and a loss of footprint from the ipsilateral hind paw was evident. Daily treatment of the animals with Hp either i.art. (10 and 20 μg/knee) or p.o. (20 μg/Kg) as well as Indo (5 mg/Kg, i.p.) ameliorated the impaired mobility in a time-dependent manner (P < 0.05). In parallel, the AIA-injected ipsilateral knee joints reach a peak of swelling 24 h after AIA induction, which persisted over the next four days in relation to PBS-injected rats or contralateral knee joints. There was a significant but not dose-dependent inhibitory effect produced by all dosages and routes of Hp treatments on AIA-induced knee joint swelling (P < 0.05). In addition, the increased synovial levels of MPO activity, total leukocytes number and IL-6, but not IL-1β, were significantly reduced by the lower i.art. dose of Hp. In conclusion, these results successfully demonstrate that Hp may represent a novel therapeutic strategy to treat RA, an effect which is unrelated to the proinflammatory actions of the neuropeptides CGRP and SP.</description><identifier>ISSN: 0014-2999</identifier><identifier>ISSN: 1879-0712</identifier><identifier>EISSN: 1879-0712</identifier><identifier>EISSN: 0014-2999</identifier><identifier>DOI: 10.1016/j.ejphar.2020.173636</identifier><identifier>PMID: 33053380</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Administration, Oral ; Animals ; Anti-Inflammatory Agents - administration & dosage ; Anti-Inflammatory Agents - pharmacology ; Antigen-induced arthritis ; Arthritis, Experimental - drug therapy ; Arthritis, Rheumatoid - drug therapy ; Behavior, Animal - drug effects ; Cytokines ; Cytokines - metabolism ; Edema - drug therapy ; Gait - drug effects ; Hemoglobins - administration & dosage ; Hemoglobins - pharmacology ; Hemopressin ; Human health and pathology ; Inflammation - drug therapy ; Injections, Intra-Articular ; Knee Joint - drug effects ; Knee Joint - metabolism ; Knee Joint - pathology ; Leukocytes - drug effects ; Life Sciences ; Male ; Neuropeptides ; Nociception ; Nociceptive Pain - prevention & control ; Peptide Fragments - administration & dosage ; Peptide Fragments - pharmacology ; Rat ; Rats ; Rats, Sprague-Dawley ; Receptors, Calcitonin Gene-Related Peptide - metabolism ; Substance P - metabolism</subject><ispartof>European journal of pharmacology, 2021-01, Vol.890, p.173636, Article 173636</ispartof><rights>2020 Elsevier B.V.</rights><rights>Copyright © 2020 Elsevier B.V. All rights reserved.</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c396t-9fe3e00176fe662ea0f3e45f59287cafc54a9bf9a9188128ecda4127bd4af59c3</citedby><cites>FETCH-LOGICAL-c396t-9fe3e00176fe662ea0f3e45f59287cafc54a9bf9a9188128ecda4127bd4af59c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0014299920307287$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,776,780,881,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33053380$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://ut3-toulouseinp.hal.science/hal-04709998$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Camargo, Livia L.</creatorcontrib><creatorcontrib>Denadai-Souza, Alexandre</creatorcontrib><creatorcontrib>Yshii, Lidia M.</creatorcontrib><creatorcontrib>Lima, Carla</creatorcontrib><creatorcontrib>Teixeira, Simone A.</creatorcontrib><creatorcontrib>Cerqueira, Anderson R.A.</creatorcontrib><creatorcontrib>Gewehr, Mayara C.F.</creatorcontrib><creatorcontrib>Fernandes, Elizabeth S.</creatorcontrib><creatorcontrib>Schenka, André A.</creatorcontrib><creatorcontrib>Muscará, Marcelo N.</creatorcontrib><creatorcontrib>Ferro, Emer S.</creatorcontrib><creatorcontrib>Costa, Soraia K.P.</creatorcontrib><title>The potential anti-inflammatory and anti-nociceptive effects of rat hemopressin (PVNFKFLSH) in experimental arthritis</title><title>European journal of pharmacology</title><addtitle>Eur J Pharmacol</addtitle><description>Inflammatory arthritis, such as rheumatoid arthritis (RA), stands out as one of the main sources of pain and impairment to the quality of life. The use of hemopressin (PVNFKFLSH; Hp), an inverse agonist of type 1 cannabinoid receptor, has proven to be effective in producing analgesia in pain models, but its effect on neuro-inflammatory aspects of RA is limited. In this study, antigen-induced arthritis (AIA) was evoked by the intraarticular (i.art.) injection of methylated bovine serum albumin (mBSA) in male Sprague Dawley rats. Phosphate buffered saline (PBS)-injected ipsilateral knee joints or AIA contralateral were used as control. Nociceptive and inflammatory parameters such as knee joint oedema and leukocyte influx and histopathological changes were carried out in addition to the local measurement of interleukins (IL) IL-6, IL-1β, tumor necrosis factor-α and the immunoreactivity of the neuropeptides substance P (SP) and calcitonin gene related peptide (CGRP) in the spinal cord (lumbar L3-5 segments) of AIA rats. For 4 days, AIA rats were treated daily with a single administration of saline, Hp injected (10 or 20 μg/day, i.art.), Hp given orally (20 μg/Kg, p.o.) or indomethacin (Indo; 5 mg/Kg, i.p.). In comparison to the PBS control group, the induction of AIA produced a significant and progressive mono-arthritis condition. The degree of AIA severity progressively compromised the normal walking pattern and impaired mobility over the next four days in relation to PBS-injected rats or contralateral knee joints. In AIA rats, the reduction of the distance between footprints and disturbances of gait evidenced signs of nociception. This response worsened at day 4, and a loss of footprint from the ipsilateral hind paw was evident. Daily treatment of the animals with Hp either i.art. (10 and 20 μg/knee) or p.o. (20 μg/Kg) as well as Indo (5 mg/Kg, i.p.) ameliorated the impaired mobility in a time-dependent manner (P < 0.05). In parallel, the AIA-injected ipsilateral knee joints reach a peak of swelling 24 h after AIA induction, which persisted over the next four days in relation to PBS-injected rats or contralateral knee joints. There was a significant but not dose-dependent inhibitory effect produced by all dosages and routes of Hp treatments on AIA-induced knee joint swelling (P < 0.05). In addition, the increased synovial levels of MPO activity, total leukocytes number and IL-6, but not IL-1β, were significantly reduced by the lower i.art. dose of Hp. In conclusion, these results successfully demonstrate that Hp may represent a novel therapeutic strategy to treat RA, an effect which is unrelated to the proinflammatory actions of the neuropeptides CGRP and SP.</description><subject>Administration, Oral</subject><subject>Animals</subject><subject>Anti-Inflammatory Agents - administration & dosage</subject><subject>Anti-Inflammatory Agents - pharmacology</subject><subject>Antigen-induced arthritis</subject><subject>Arthritis, Experimental - drug therapy</subject><subject>Arthritis, Rheumatoid - drug therapy</subject><subject>Behavior, Animal - drug effects</subject><subject>Cytokines</subject><subject>Cytokines - metabolism</subject><subject>Edema - drug therapy</subject><subject>Gait - drug effects</subject><subject>Hemoglobins - administration & dosage</subject><subject>Hemoglobins - pharmacology</subject><subject>Hemopressin</subject><subject>Human health and pathology</subject><subject>Inflammation - drug therapy</subject><subject>Injections, Intra-Articular</subject><subject>Knee Joint - drug effects</subject><subject>Knee Joint - metabolism</subject><subject>Knee Joint - pathology</subject><subject>Leukocytes - drug effects</subject><subject>Life Sciences</subject><subject>Male</subject><subject>Neuropeptides</subject><subject>Nociception</subject><subject>Nociceptive Pain - prevention & control</subject><subject>Peptide Fragments - administration & dosage</subject><subject>Peptide Fragments - pharmacology</subject><subject>Rat</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Receptors, Calcitonin Gene-Related Peptide - metabolism</subject><subject>Substance P - metabolism</subject><issn>0014-2999</issn><issn>1879-0712</issn><issn>1879-0712</issn><issn>0014-2999</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kEtLAzEUhYMotj7-gcgs7WJqMplXNkIp1opFBavbkGZumAzzIkmL_femjHbp6pLDOTf3fAjdEDwlmKT31RSqvhRmGuHISxlNaXqCxiTPWIgzEp2iMcYkDiPG2AhdWFthjBMWJedoRClOKM3xGG3XJQR956B1WtSB8CPUrapF0wjXmb1XikFtO6kl9E7vIAClQDobdCowwgUlNF1vwFrdBnfvX6-Ll8XqYzkJ_BO-ezC68esP240rjXbaXqEzJWoL17_zEn0uHtfzZbh6e3qez1ahpCx1IVNAwZfIUgVpGoHAikKcKN8iz6RQMokF2ygmGMlzEuUgCxGTKNsUsfAmSS_RZNhbipr3_g5h9rwTmi9nK37QcJxhzyffEe-NB680nbUG1DFAMD8Q5xUfiPMDcT4Q97HbIdZvNw0Ux9AfYm94GAzgi-40GG6lhlZCoY2HyItO___DD6aUlQ0</recordid><startdate>20210105</startdate><enddate>20210105</enddate><creator>Camargo, Livia L.</creator><creator>Denadai-Souza, Alexandre</creator><creator>Yshii, Lidia M.</creator><creator>Lima, Carla</creator><creator>Teixeira, Simone A.</creator><creator>Cerqueira, Anderson R.A.</creator><creator>Gewehr, Mayara C.F.</creator><creator>Fernandes, Elizabeth S.</creator><creator>Schenka, André A.</creator><creator>Muscará, Marcelo N.</creator><creator>Ferro, Emer S.</creator><creator>Costa, Soraia K.P.</creator><general>Elsevier B.V</general><general>Elsevier</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>1XC</scope></search><sort><creationdate>20210105</creationdate><title>The potential anti-inflammatory and anti-nociceptive effects of rat hemopressin (PVNFKFLSH) in experimental arthritis</title><author>Camargo, Livia L. ; Denadai-Souza, Alexandre ; Yshii, Lidia M. ; Lima, Carla ; Teixeira, Simone A. ; Cerqueira, Anderson R.A. ; Gewehr, Mayara C.F. ; Fernandes, Elizabeth S. ; Schenka, André A. ; Muscará, Marcelo N. ; Ferro, Emer S. ; Costa, Soraia K.P.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c396t-9fe3e00176fe662ea0f3e45f59287cafc54a9bf9a9188128ecda4127bd4af59c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Administration, Oral</topic><topic>Animals</topic><topic>Anti-Inflammatory Agents - administration & dosage</topic><topic>Anti-Inflammatory Agents - pharmacology</topic><topic>Antigen-induced arthritis</topic><topic>Arthritis, Experimental - drug therapy</topic><topic>Arthritis, Rheumatoid - drug therapy</topic><topic>Behavior, Animal - drug effects</topic><topic>Cytokines</topic><topic>Cytokines - metabolism</topic><topic>Edema - drug therapy</topic><topic>Gait - drug effects</topic><topic>Hemoglobins - administration & dosage</topic><topic>Hemoglobins - pharmacology</topic><topic>Hemopressin</topic><topic>Human health and pathology</topic><topic>Inflammation - drug therapy</topic><topic>Injections, Intra-Articular</topic><topic>Knee Joint - drug effects</topic><topic>Knee Joint - metabolism</topic><topic>Knee Joint - pathology</topic><topic>Leukocytes - drug effects</topic><topic>Life Sciences</topic><topic>Male</topic><topic>Neuropeptides</topic><topic>Nociception</topic><topic>Nociceptive Pain - prevention & control</topic><topic>Peptide Fragments - administration & dosage</topic><topic>Peptide Fragments - pharmacology</topic><topic>Rat</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Receptors, Calcitonin Gene-Related Peptide - metabolism</topic><topic>Substance P - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Camargo, Livia L.</creatorcontrib><creatorcontrib>Denadai-Souza, Alexandre</creatorcontrib><creatorcontrib>Yshii, Lidia M.</creatorcontrib><creatorcontrib>Lima, Carla</creatorcontrib><creatorcontrib>Teixeira, Simone A.</creatorcontrib><creatorcontrib>Cerqueira, Anderson R.A.</creatorcontrib><creatorcontrib>Gewehr, Mayara C.F.</creatorcontrib><creatorcontrib>Fernandes, Elizabeth S.</creatorcontrib><creatorcontrib>Schenka, André A.</creatorcontrib><creatorcontrib>Muscará, Marcelo N.</creatorcontrib><creatorcontrib>Ferro, Emer S.</creatorcontrib><creatorcontrib>Costa, Soraia K.P.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Hyper Article en Ligne (HAL)</collection><jtitle>European journal of pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Camargo, Livia L.</au><au>Denadai-Souza, Alexandre</au><au>Yshii, Lidia M.</au><au>Lima, Carla</au><au>Teixeira, Simone A.</au><au>Cerqueira, Anderson R.A.</au><au>Gewehr, Mayara C.F.</au><au>Fernandes, Elizabeth S.</au><au>Schenka, André A.</au><au>Muscará, Marcelo N.</au><au>Ferro, Emer S.</au><au>Costa, Soraia K.P.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The potential anti-inflammatory and anti-nociceptive effects of rat hemopressin (PVNFKFLSH) in experimental arthritis</atitle><jtitle>European journal of pharmacology</jtitle><addtitle>Eur J Pharmacol</addtitle><date>2021-01-05</date><risdate>2021</risdate><volume>890</volume><spage>173636</spage><pages>173636-</pages><artnum>173636</artnum><issn>0014-2999</issn><issn>1879-0712</issn><eissn>1879-0712</eissn><eissn>0014-2999</eissn><abstract>Inflammatory arthritis, such as rheumatoid arthritis (RA), stands out as one of the main sources of pain and impairment to the quality of life. The use of hemopressin (PVNFKFLSH; Hp), an inverse agonist of type 1 cannabinoid receptor, has proven to be effective in producing analgesia in pain models, but its effect on neuro-inflammatory aspects of RA is limited. In this study, antigen-induced arthritis (AIA) was evoked by the intraarticular (i.art.) injection of methylated bovine serum albumin (mBSA) in male Sprague Dawley rats. Phosphate buffered saline (PBS)-injected ipsilateral knee joints or AIA contralateral were used as control. Nociceptive and inflammatory parameters such as knee joint oedema and leukocyte influx and histopathological changes were carried out in addition to the local measurement of interleukins (IL) IL-6, IL-1β, tumor necrosis factor-α and the immunoreactivity of the neuropeptides substance P (SP) and calcitonin gene related peptide (CGRP) in the spinal cord (lumbar L3-5 segments) of AIA rats. For 4 days, AIA rats were treated daily with a single administration of saline, Hp injected (10 or 20 μg/day, i.art.), Hp given orally (20 μg/Kg, p.o.) or indomethacin (Indo; 5 mg/Kg, i.p.). In comparison to the PBS control group, the induction of AIA produced a significant and progressive mono-arthritis condition. The degree of AIA severity progressively compromised the normal walking pattern and impaired mobility over the next four days in relation to PBS-injected rats or contralateral knee joints. In AIA rats, the reduction of the distance between footprints and disturbances of gait evidenced signs of nociception. This response worsened at day 4, and a loss of footprint from the ipsilateral hind paw was evident. Daily treatment of the animals with Hp either i.art. (10 and 20 μg/knee) or p.o. (20 μg/Kg) as well as Indo (5 mg/Kg, i.p.) ameliorated the impaired mobility in a time-dependent manner (P < 0.05). In parallel, the AIA-injected ipsilateral knee joints reach a peak of swelling 24 h after AIA induction, which persisted over the next four days in relation to PBS-injected rats or contralateral knee joints. There was a significant but not dose-dependent inhibitory effect produced by all dosages and routes of Hp treatments on AIA-induced knee joint swelling (P < 0.05). In addition, the increased synovial levels of MPO activity, total leukocytes number and IL-6, but not IL-1β, were significantly reduced by the lower i.art. dose of Hp. In conclusion, these results successfully demonstrate that Hp may represent a novel therapeutic strategy to treat RA, an effect which is unrelated to the proinflammatory actions of the neuropeptides CGRP and SP.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>33053380</pmid><doi>10.1016/j.ejphar.2020.173636</doi></addata></record> |
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| subjects | Administration, Oral Animals Anti-Inflammatory Agents - administration & dosage Anti-Inflammatory Agents - pharmacology Antigen-induced arthritis Arthritis, Experimental - drug therapy Arthritis, Rheumatoid - drug therapy Behavior, Animal - drug effects Cytokines Cytokines - metabolism Edema - drug therapy Gait - drug effects Hemoglobins - administration & dosage Hemoglobins - pharmacology Hemopressin Human health and pathology Inflammation - drug therapy Injections, Intra-Articular Knee Joint - drug effects Knee Joint - metabolism Knee Joint - pathology Leukocytes - drug effects Life Sciences Male Neuropeptides Nociception Nociceptive Pain - prevention & control Peptide Fragments - administration & dosage Peptide Fragments - pharmacology Rat Rats Rats, Sprague-Dawley Receptors, Calcitonin Gene-Related Peptide - metabolism Substance P - metabolism |
| title | The potential anti-inflammatory and anti-nociceptive effects of rat hemopressin (PVNFKFLSH) in experimental arthritis |
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