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Thus, research on new strategies to effectively relieve nociceptive and\/or emotional disorders accompanying chronic pain is essential. Several studies have demonstrated the anti\u2010inflammatory and antinociceptive effects of different carbon monoxide\u2010releasing molecules (CO\u2010RMs), inducible heme oxygenase 1 (HO\u20101), and nuclear factor\u20102 erythroid factor\u20102 (Nrf2) transcription factor activators in several models of acute and chronic pain caused by inflammation, nerve injury or diabetes. More recently, the antidepressant and\/or anxiolytic effects of several Nrf2 transcription factor inducers were demonstrated in a model of chronic neuropathic pain. These effects are mainly produced by inhibition of oxidative stress, inflammation, glial activation, mitogen\u2010activated protein kinases and\/or phosphoinositide 3\u2010kinase\/phospho\u2010protein kinase B phosphorylation in the peripheral and\/or central nervous system. Other studies also demonstrated that the analgesic effects of opioids and cannabinoids are improved when these drugs are coadministered with CO\u2010RMs, HO\u20101 or Nrf2 activators in different preclinical pain models and that these improvements are generally mediated by upregulation or prevention of the downregulation of \u00b5\u2010opioid receptors, \u03b4\u2010opioid receptors and\/or cannabinoid 2 receptors in the setting of chronic pain. We reviewed all these studies as well as studies on the mechanisms of action underlying the effects of CO\u2010RMs, HO\u20101, and Nrf2 activators in chronic pain. In summary, activation of the Nrf2\/HO\u20101\/carbon monoxide signaling pathway alone and\/or in combination with the administration of specific analgesics is a valid strategy for the treatment of chronic pain and some associated emotional disorders.<\/jats:p>","DOI":"10.1002\/med.21726","type":"journal-article","created":{"date-parts":[[2020,8,21]],"date-time":"2020-08-21T10:10:05Z","timestamp":1598004605000},"page":"136-155","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["The role of carbon monoxide, heme oxygenase 1, and the Nrf2 transcription factor in the modulation of chronic pain and their interactions with opioids and cannabinoids"],"prefix":"10.1002","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4621-8457","authenticated-orcid":false,"given":"Olga","family":"Pol","sequence":"first","affiliation":[{"name":"Grup de Neurofarmacologia Molecular, Institut d'Investigaci\u00f3 Biom\u00e8dica Sant Pau Hospital de la Santa Creu i Sant Pau  Barcelona Spain"},{"name":"Grup de Neurofarmacologia Molecular, Institut de Neuroci\u00e8ncies Universitat Aut\u00f2noma de Barcelona  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,8,20]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.4081\/reumatismo.2015.840"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.2741\/3598"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2011.09.014"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/fampra\/cmx034"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1037\/a0013628"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2017.2"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-200603000-00025"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pmr.2020.01.002"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2020.00478"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcna.2015.08.006"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2007.082412"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2007.09.015"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1097\/ALN.0b013e318286d085"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-013-3302-7"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0043693"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20092211"},{"key":"e_1_2_10_18_1","first-page":"220","article-title":"Spinal 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