Hydrogen Sulfide Interacting with Cannabinoid 2 Receptors during Sciatic Nerve Injury-Induced Neuropathic Pain
Bai, Xue (Institut d'Investigació Biomèdica Sant Pau)
Batallé Melgarejo, Gerard (Institut d'Investigació Biomèdica Sant Pau)
Martínez-Martel, Ignacio (Institut d'Investigació Biomèdica Sant Pau)
Pol, Olga (Institut d'Investigació Biomèdica Sant Pau)
Universitat Autònoma de Barcelona

Fecha:	2023
Resumen:	Hydrogen sulfide (HS) donors make opioids more effective in inhibiting nociception during inflammatory and neuropathic pain. We examined whether the analgesic, anxiolytic and/or antidepressant actions of the cannabinoid 2 receptor (CB2R) agonist, JWH-133, might be improved by pretreatment with HS donors, DADS and GYY4137 in mice with sciatic nerve injury-provoked neuropathy (CCI). The reversion of the antinociceptive effects of these treatments with the CB2R antagonist, AM630, and the regulatory actions of HS in the phosphorylation of NF-κB inhibitor alpha (IKBα) and in the brain-derived neurotrophic factor (BDNF), CB2R, Nrf2 and heme oxygenase 1 (HO-1) levels in prefrontal cortex (PFC), ventral hippocampus (vHIP) and periaqueductal gray matter (PAG), were examined. Data showed that the analgesic effects of JWH-133, systemically and locally administered, were improved by the DADS or GYY4137 pretreatment. The co-treatment of GYY4137 with JWH-133 also stopped anxiodepressive-like activities that concur with neuropathy. Our data likewise showed that both HS donors normalized the inflammatory (p-IKBα), neurotrophic (BDNF) variations caused by CCI, increased the expression of CB2R and activated the Nrf2/HO-1 antioxidant pathway in PFC, v-HIP and/or PAG of animals with neuropathic pain. In addition, the blockade of the analgesia produced by high doses of DADS and GYY4137 with AM630 indicated the contribution of the endocannabinoid system in the effects of HS during neuropathic pain, thus supporting the positive interaction between HS and CB2R. Therefore, this study demonstrates the potential use of CB2R agonists combined with HS donors as a possible treatment for peripheral nerve injury-caused neuropathic pain and the associated emotional disturbances.
Ayudas:	Instituto de Salud Carlos III PI18/00645 Instituto de Salud Carlos III PI21/00592
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Analgesia ; Anxiety ; BDNF ; Cannabinoids ; Cannabinoid 2 receptors ; Depression ; Hydrogen sulfide ; Neuropathic pain ; Oxidative stress
Publicado en:	Antioxidants, Vol. 12 (may 2023) , ISSN 2076-3921

DOI: 10.3390/antiox12061179
PMID: 37371911

19 p, 3.9 MB

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