Antinociception synergy between the peripheral and spinal sites of the heme oxygenase-carbon monoxide pathway
We have shown that the peripheral and spinal cord heme oxygenase (HO)-carbon monoxide (CO)-soluble guanylate cyclase-cGMP pathways play an important role in antinociception in the rat experimental formalin model. Our objective was to determine if there is synergism between peripheral (paw) and spina...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
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Associação Brasileira de Divulgação Científica
2009-01-01
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| Series: | Brazilian Journal of Medical and Biological Research |
| Subjects: | |
| Online Access: | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2009000100020 |
| _version_ | 1818133829356879872 |
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| author | C.G.O. Nascimento L.G.S. Branco |
| author_facet | C.G.O. Nascimento L.G.S. Branco |
| author_sort | C.G.O. Nascimento |
| collection | DOAJ |
| description | We have shown that the peripheral and spinal cord heme oxygenase (HO)-carbon monoxide (CO)-soluble guanylate cyclase-cGMP pathways play an important role in antinociception in the rat experimental formalin model. Our objective was to determine if there is synergism between peripheral (paw) and spinal HO-CO pathways in nociception. Rats were handled and adapted to the experimental environment for a few days before the formalin test, in which 50 µL of a 1% formalin was injected subcutaneously into the dorsal surface of the right hind paw. The animals were then observed for 1 h and the frequency of flinching behavior was taken to represent the nociceptive response. Thirty minutes before the test, rats were pretreated with intrathecal injections of the HO inhibitor, zinc deuteroporphyrin 2,4-bis glycol (ZnDPBG) or heme-lysinate, which is a substrate of the HO pathway. The paw treatments took place 20 min before the test. Low doses of ZnDPBG did not increase nociception, while a low heme-lysinate dose did not change flinching behavior after paw or spinal injections. Combined subactive spinal (50 nmol) and peripheral (40 nmol) low doses of ZnDPBG induced hypernociception (increase of 80% in the first and 25% in the second phase flinching), whereas combined spinal-peripheral heme-lysinate (50 and 30 nmol) led to second phase antinociception (40% reduction in flinching). These findings suggest a synergy between the peripheral and spinal HO-CO pathways. Local activation of the HO system probably regulates the nociception initiation in peripheral tissue and participates in buffering the emerging nociceptive signals at the peripheral and spinal sites of action. In short, an antinociceptive synergy exists between peripheral and spinal HO pathways, which may reduce the doses required and side effects. |
| first_indexed | 2024-12-11T08:58:56Z |
| format | Article |
| id | doaj.art-b1c2f61ecdb7493da5cf7384a604f3bd |
| institution | Directory Open Access Journal |
| issn | 0100-879X 1414-431X |
| language | English |
| last_indexed | 2024-12-11T08:58:56Z |
| publishDate | 2009-01-01 |
| publisher | Associação Brasileira de Divulgação Científica |
| record_format | Article |
| series | Brazilian Journal of Medical and Biological Research |
| spelling | doaj.art-b1c2f61ecdb7493da5cf7384a604f3bd2022-12-22T01:13:48ZengAssociação Brasileira de Divulgação CientíficaBrazilian Journal of Medical and Biological Research0100-879X1414-431X2009-01-01421141147Antinociception synergy between the peripheral and spinal sites of the heme oxygenase-carbon monoxide pathwayC.G.O. NascimentoL.G.S. BrancoWe have shown that the peripheral and spinal cord heme oxygenase (HO)-carbon monoxide (CO)-soluble guanylate cyclase-cGMP pathways play an important role in antinociception in the rat experimental formalin model. Our objective was to determine if there is synergism between peripheral (paw) and spinal HO-CO pathways in nociception. Rats were handled and adapted to the experimental environment for a few days before the formalin test, in which 50 µL of a 1% formalin was injected subcutaneously into the dorsal surface of the right hind paw. The animals were then observed for 1 h and the frequency of flinching behavior was taken to represent the nociceptive response. Thirty minutes before the test, rats were pretreated with intrathecal injections of the HO inhibitor, zinc deuteroporphyrin 2,4-bis glycol (ZnDPBG) or heme-lysinate, which is a substrate of the HO pathway. The paw treatments took place 20 min before the test. Low doses of ZnDPBG did not increase nociception, while a low heme-lysinate dose did not change flinching behavior after paw or spinal injections. Combined subactive spinal (50 nmol) and peripheral (40 nmol) low doses of ZnDPBG induced hypernociception (increase of 80% in the first and 25% in the second phase flinching), whereas combined spinal-peripheral heme-lysinate (50 and 30 nmol) led to second phase antinociception (40% reduction in flinching). These findings suggest a synergy between the peripheral and spinal HO-CO pathways. Local activation of the HO system probably regulates the nociception initiation in peripheral tissue and participates in buffering the emerging nociceptive signals at the peripheral and spinal sites of action. In short, an antinociceptive synergy exists between peripheral and spinal HO pathways, which may reduce the doses required and side effects.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2009000100020NociceptionCarbon monoxideFormalinHypernociceptionAntinociception |
| spellingShingle | C.G.O. Nascimento L.G.S. Branco Antinociception synergy between the peripheral and spinal sites of the heme oxygenase-carbon monoxide pathway Brazilian Journal of Medical and Biological Research Nociception Carbon monoxide Formalin Hypernociception Antinociception |
| title | Antinociception synergy between the peripheral and spinal sites of the heme oxygenase-carbon monoxide pathway |
| title_full | Antinociception synergy between the peripheral and spinal sites of the heme oxygenase-carbon monoxide pathway |
| title_fullStr | Antinociception synergy between the peripheral and spinal sites of the heme oxygenase-carbon monoxide pathway |
| title_full_unstemmed | Antinociception synergy between the peripheral and spinal sites of the heme oxygenase-carbon monoxide pathway |
| title_short | Antinociception synergy between the peripheral and spinal sites of the heme oxygenase-carbon monoxide pathway |
| title_sort | antinociception synergy between the peripheral and spinal sites of the heme oxygenase carbon monoxide pathway |
| topic | Nociception Carbon monoxide Formalin Hypernociception Antinociception |
| url | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2009000100020 |
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