{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T15:48:33Z","timestamp":1791906513692,"version":"4.3.4"},"reference-count":73,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2011,12,19]],"date-time":"2011-12-19T00:00:00Z","timestamp":1324252800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["European Journal of Pain"],"published-print":{"date-parts":[[2012,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The most commonly used drugs against pain act by inhibiting the cyclooxygenases (<jats:styled-content style=\"fixed-case\">COXs<\/jats:styled-content>). Metamizol (dipyrone) inhibits the<jats:styled-content style=\"fixed-case\">COXs<\/jats:styled-content>and is widely used in<jats:styled-content style=\"fixed-case\">E<\/jats:styled-content>urope and<jats:styled-content style=\"fixed-case\">L<\/jats:styled-content>atin<jats:styled-content style=\"fixed-case\">A<\/jats:styled-content>merica as a non\u2010opioid analgesic. One target of metamizol and other non\u2010opioid analgesics is the periaqueductal grey matter (<jats:styled-content style=\"fixed-case\">PAG<\/jats:styled-content>), where they trigger descending inhibition of spinal nociceptive transmission. Also, cannabinoids exert an analgesic action at several structures in the peripheral and central nervous system, including the<jats:styled-content style=\"fixed-case\">PAG<\/jats:styled-content>. The present study investigates whether the antinociceptive action of metamizol in the lateral\u2010ventrolateral (<jats:styled-content style=\"fixed-case\">LVL<\/jats:styled-content>)<jats:styled-content style=\"fixed-case\">PAG<\/jats:styled-content>during inflammation is related to endocannabinoids. In anaesthetized rats, unitary action potentials were recorded from spinal nociceptive neurons with receptive fields in the ipsilateral hind paw. Inflammation of the paw induced neuronal hyperexcitability, which was attenuated by intra\u2010<jats:styled-content style=\"fixed-case\">LVL\u2010PAG<\/jats:styled-content>microinjection of metamizol either at the beginning of inflammation or when hyperexcitability was fully established. In both cases, the antinociceptive effect of metamizol was reduced by a microinjection of<jats:styled-content style=\"fixed-case\">AM251<\/jats:styled-content>, an antagonist at the<jats:styled-content style=\"fixed-case\">CB1<\/jats:styled-content>cannabinoid receptor, either into the<jats:styled-content style=\"fixed-case\">LVL\u2010PAG<\/jats:styled-content>or into the rostral ventromedial medulla (<jats:styled-content style=\"fixed-case\">RVM<\/jats:styled-content>). The<jats:styled-content style=\"fixed-case\">RVM<\/jats:styled-content>is a downstream structure that funnels<jats:styled-content style=\"fixed-case\">PAG<\/jats:styled-content>\u2010derived descending inhibition into the spinal cord. These results show that endocannabinoids and their<jats:styled-content style=\"fixed-case\">CB1<\/jats:styled-content>receptor (1) contribute at the<jats:styled-content style=\"fixed-case\">LVL\u2010PAG<\/jats:styled-content>to the antinociceptive effects of metamizol, and possibly other non\u2010opioid analgesics; and (2) participate in the<jats:styled-content style=\"fixed-case\">PAG<\/jats:styled-content>\u2010derived activation of<jats:styled-content style=\"fixed-case\">RVM<\/jats:styled-content>descending antinociceptive influences.<\/jats:p>","DOI":"10.1002\/j.1532-2149.2011.00057.x","type":"journal-article","created":{"date-parts":[[2011,12,22]],"date-time":"2011-12-22T11:42:51Z","timestamp":1324554171000},"page":"676-689","source":"Crossref","is-referenced-by-count":52,"title":["Metamizol, a non\u2010opioid analgesic, acts via endocannabinoids in the<scp>PAG\u2010RVM<\/scp>axis during inflammation in rats"],"prefix":"10.1002","volume":"16","author":[{"given":"W.","family":"Escobar","sequence":"first","affiliation":[{"name":"Centro de Biof\u00edsica y Bioqu\u00edmica Instituto Venezolano de Investigaciones Cient\u00edficas (IVIC) Apartado 20632 Caracas 1020\u2010A Venezuela"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Ramirez","sequence":"additional","affiliation":[{"name":"Centro de Biof\u00edsica y Bioqu\u00edmica Instituto Venezolano de Investigaciones Cient\u00edficas (IVIC) Apartado 20632 Caracas 1020\u2010A Venezuela"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Avila","sequence":"additional","affiliation":[{"name":"Centro de Biof\u00edsica y Bioqu\u00edmica Instituto Venezolano de Investigaciones Cient\u00edficas (IVIC) Apartado 20632 Caracas 1020\u2010A Venezuela"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Limongi","sequence":"additional","affiliation":[{"name":"Centro de Biof\u00edsica y Bioqu\u00edmica Instituto Venezolano de Investigaciones Cient\u00edficas (IVIC) Apartado 20632 Caracas 1020\u2010A Venezuela"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.","family":"Vanegas","sequence":"additional","affiliation":[{"name":"Centro de Biof\u00edsica y Bioqu\u00edmica Instituto Venezolano de Investigaciones Cient\u00edficas (IVIC) Apartado 20632 Caracas 1020\u2010A Venezuela"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Vazquez","sequence":"additional","affiliation":[{"name":"Centro de Biof\u00edsica y Bioqu\u00edmica Instituto Venezolano de Investigaciones Cient\u00edficas (IVIC) Apartado 20632 Caracas 1020\u2010A Venezuela"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2011,12,19]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresrev.2008.12.003"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2010.00729.x"},{"key":"e_1_2_6_4_1","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1523\/JNEUROSCI.0882-03.2004","article-title":"Changes in the effect of spinal prostaglandin E2 during inflammation: Prostaglandin E (EP1\u2010EP4) receptors in spinal nociceptive processing of input from the normal or inflamed knee joint","volume":"24","author":"B\u00e4r K\u2010J","year":"2004","journal-title":"J Neurosci"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.903220309"},{"key":"e_1_2_6_6_1","volume-title":"Goodman & Gilman's the pharmacological basis of therapeutics","author":"Brunton LL","year":"2006"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(99)00477-X"},{"key":"e_1_2_6_8_1","volume-title":"Los Analgesicos Antitermicos","author":"Ceraso OL","year":"1994"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.162468699"},{"key":"e_1_2_6_10_1","first-page":"1760","article-title":"Biopharmazeutische und pharmakokinetische untersuchungen nach Gabe von Metamizol\u201014C (NovalginR 14C) an ratte, Hund und Mensch","volume":"23","author":"Christ O","year":"1973","journal-title":"Arneim\u2010Forsch (Drug Res)"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s000110050367"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s002280050511"},{"key":"e_1_2_6_13_1","volume-title":"Practical nonparametric statistics","author":"Conover WJ","year":"1980"},{"issue":"9","key":"e_1_2_6_14_1","doi-asserted-by":"crossref","DOI":"10.1002\/14651858.CD003227.pub2","article-title":"Single dose dipyrone for acute postoperative pain","author":"Derry S","year":"2010","journal-title":"Cochrane Database Syst Rev"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1431"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbb.2005.01.023"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(96)00279-8"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0024-3205(97)00690-5"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(02)02485-8"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2004.04.026"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(94)90548-7"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(01)02085-6"},{"key":"e_1_2_6_23_1","volume-title":"Novalgin","author":"Hoechst","year":"1996"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1208\/aapsj080479"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature03658"},{"key":"e_1_2_6_26_1","volume-title":"Management of acute pain: a practical guide","author":"IASP","year":"1992"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2005.12.018"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2008.06162.x"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0090-6980(97)00128-7"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn1262"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0028-3908(01)00100-9"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M206788200"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M007088200"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2586-07.2007"},{"key":"e_1_2_6_35_1","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1016\/S0022-3565(25)12310-0","article-title":"Investigation of brain sites mediating cannabinoid\u2010induced antinociception in rats: evidence supporting periaqueductal gray involvement","volume":"276","author":"Lichtman AH","year":"1996","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1021\/pr900106v"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3940(98)00044-5"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2008.11.015"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/26481"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(86)91367-3"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.2042-7158.1985.tb03030.x"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2005.11.025"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1009532107"},{"key":"e_1_2_6_44_1","volume-title":"A stereotaxic atlas of the rat brain","author":"Pellegrino LJ","year":"1979"},{"key":"e_1_2_6_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2004.06.006"},{"key":"e_1_2_6_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0707239"},{"key":"e_1_2_6_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1247"},{"key":"e_1_2_6_48_1","doi-asserted-by":"publisher","DOI":"10.1097\/ALN.0b013e318167af74"},{"key":"e_1_2_6_49_1","volume-title":"Handbook of nonparametric and parametric statistical procedures","author":"Sheskin DJ","year":"2004"},{"key":"e_1_2_6_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0361-9230(02)00872-9"},{"key":"e_1_2_6_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2005.07.007"},{"key":"e_1_2_6_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2009.08.013"},{"key":"e_1_2_6_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2004.08.006"},{"key":"e_1_2_6_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3959(94)90224-0"},{"key":"e_1_2_6_55_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.1995.tb00706.x"},{"key":"e_1_2_6_56_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1460-9568.2000.00295.x"},{"key":"e_1_2_6_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(96)00196-5"},{"key":"e_1_2_6_58_1","doi-asserted-by":"publisher","DOI":"10.1038\/newbio231232a0"},{"key":"e_1_2_6_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(84)90689-9"},{"key":"e_1_2_6_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0301-0082(00)00063-0"},{"key":"e_1_2_6_61_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1021896622089"},{"key":"e_1_2_6_62_1","first-page":"69","volume-title":"Neurotransmission in the antinociceptive descending pathway","author":"Vanegas H","year":"2007"},{"key":"e_1_2_6_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(97)00360-0"},{"key":"e_1_2_6_64_1","doi-asserted-by":"crossref","first-page":"9001","DOI":"10.1523\/JNEUROSCI.21-22-09001.2001","article-title":"Spinal prostaglandins are involved in the development but not the maintenance of inflammation\u2010induced spinal hyperexcitability","volume":"21","author":"Vasquez E","year":"2001","journal-title":"J Neurosci"},{"key":"e_1_2_6_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(99)02303-3"},{"key":"e_1_2_6_66_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0701818"},{"key":"e_1_2_6_67_1","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1016\/S0026-895X(24)23200-4","article-title":"Actions of cannabinoids on membrane properties and synaptic transmission in rat periaqueductal gray neurons in vitro","volume":"57","author":"Vaughan CW","year":"2000","journal-title":"Mol Pharmacol"},{"key":"e_1_2_6_68_1","doi-asserted-by":"publisher","DOI":"10.1038\/37610"},{"key":"e_1_2_6_69_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0702636"},{"key":"e_1_2_6_70_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2007.05280.x"},{"key":"e_1_2_6_71_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2005.04.083"},{"key":"e_1_2_6_72_1","unstructured":"Vazquez\u2010RodriguezE EscobarW RamirezK AvilaC VanegasH.The antihyperalgesic effect of PAG\u2010microinjected metamizol is mediated by endocannabinoids in the PAG\u2010RVM axis. 12th World Congress on Pain Glasgow IASP Press Seattle;2008. Abstract Nr 2515."},{"key":"e_1_2_6_73_1","first-page":"311","volume-title":"Proceedings of the 11th World Congress on Pain","author":"Wessendorf MW","year":"2006"},{"key":"e_1_2_6_74_1","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(93)90192-T"}],"container-title":["European Journal of Pain"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fj.1532-2149.2011.00057.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/j.1532-2149.2011.00057.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,16]],"date-time":"2025-03-16T11:03:09Z","timestamp":1742122989000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/j.1532-2149.2011.00057.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,12,19]]},"references-count":73,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2012,5]]}},"alternative-id":["10.1002\/j.1532-2149.2011.00057.x"],"URL":"https:\/\/doi.org\/10.1002\/j.1532-2149.2011.00057.x","archive":["Portico"],"relation":{},"ISSN":["1090-3801","1532-2149"],"issn-type":[{"value":"1090-3801","type":"print"},{"value":"1532-2149","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,12,19]]}}}