TY - JOUR
T1 - 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
AU - Pol, Olga
N1 - Publisher Copyright:
© 2020 Wiley Periodicals LLC
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020
Y1 - 2020
N2 - Chronic pain and its associated comorbidities are difficult to treat, even when the most potent analgesic compounds are used. Thus, research on new strategies to effectively relieve nociceptive and/or emotional disorders accompanying chronic pain is essential. Several studies have demonstrated the anti-inflammatory and antinociceptive effects of different carbon monoxide-releasing molecules (CO-RMs), inducible heme oxygenase 1 (HO-1), and nuclear factor-2 erythroid factor-2 (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-activated protein kinases and/or phosphoinositide 3-kinase/phospho-protein 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-RMs, HO-1 or Nrf2 activators in different preclinical pain models and that these improvements are generally mediated by upregulation or prevention of the downregulation of µ-opioid receptors, δ-opioid 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-RMs, HO-1, and Nrf2 activators in chronic pain. In summary, activation of the Nrf2/HO-1/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.
AB - Chronic pain and its associated comorbidities are difficult to treat, even when the most potent analgesic compounds are used. Thus, research on new strategies to effectively relieve nociceptive and/or emotional disorders accompanying chronic pain is essential. Several studies have demonstrated the anti-inflammatory and antinociceptive effects of different carbon monoxide-releasing molecules (CO-RMs), inducible heme oxygenase 1 (HO-1), and nuclear factor-2 erythroid factor-2 (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-activated protein kinases and/or phosphoinositide 3-kinase/phospho-protein 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-RMs, HO-1 or Nrf2 activators in different preclinical pain models and that these improvements are generally mediated by upregulation or prevention of the downregulation of µ-opioid receptors, δ-opioid 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-RMs, HO-1, and Nrf2 activators in chronic pain. In summary, activation of the Nrf2/HO-1/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.
KW - cannabinoids
KW - carbon monoxide
KW - heme oxygenase 1
KW - Nrf2 transcription factor
KW - opioids
KW - pain
UR - http://www.scopus.com/inward/record.url?scp=85089594919&partnerID=8YFLogxK
U2 - 10.1002/med.21726
DO - 10.1002/med.21726
M3 - Artículo de revisión
C2 - 32820550
AN - SCOPUS:85089594919
JO - Medicinal Research Reviews
JF - Medicinal Research Reviews
SN - 0198-6325
ER -