Venlafaxine prevents morphine antinociceptive tolerance: the role of neuroinflammation and the l-arginine-nitric oxide pathway

Mansouri, Mohammad Taghi; Naghizadeh, Bahareh; Ghorbanzadeh, Behnam; Alboghobeish, Soheila; Amirgholami, Neda; Houshmand, Gholamreza; Cauli, Omar

doi:10.1016/j.expneurol.2018.02.009

Cited by 39Pain Mechanisms and TreatmentsNeuropeptides and Animal PhysiologyPain Management and Opioid Use

Venlafaxine prevents morphine antinociceptive tolerance: the role of neuroinflammation and the l-arginine-nitric oxide pathway

Mansouri, Mohammad Taghi, Naghizadeh, Bahareh, Ghorbanzadeh, Behnam, Alboghobeish, Soheila, Amirgholami, Neda, Houshmand, Gholamreza, Cauli, Omar·2018·Experimental Neurology

DOI 10.1016/j.expneurol.2018.02.009

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Abstract

Opioid-induced neuroinflammation and the nitric oxide (NO) signal-transduction pathway are involved in the development of opioid analgesic tolerance. The antidepressant venlafaxine (VLF) modulates NO in nervous tissues, and so we investigated its effect on induced tolerance to morphine, neuroinflammation, and oxidative stress in mice. Tolerance to the analgesic effects of morphine were induced by injecting mice with morphine (50 mg/kg) once a day for three consecutive days; the effect of co-administration of VLF (5 or 40 mg/kg) with morphine was similarly tested in a separate group. To determine if the NO precursor l-arginine hydrochloride (l-arg) or NO are involved in the effects rendered by VLF, animals were pre-treated with l-arg (200 mg/kg), or the NO synthesis inhibitors N(ω)-nitro-l-arginine methyl ester (L-NAME; 30 mg/kg) or aminoguanidine hydrochloride (AG; 100 mg/kg), along with VLF (40 mg/kg) for three days before receiving morphine for another three days. Nociception was assessed with a hot-plate test on the fourth day, and the concentration of tumor necrosis factor alpha (TNF-α), interleukin-1beta (IL-1β), interleukin-6 (IL-6), interleukin-10, brain-derived neurotrophic factor, NO, and oxidative stress factors such as total thiol, malondialdehyde content, and glutathione peroxidase (GPx) activity in the brain was also determined. Co-administration of VLF with morphine attenuated morphine-induced analgesic tolerance and prevented the upregulation of proinflammatory…

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Vitamin and mineral deficiencies associated with opioid addiction have been well-described.
“Vitamin and mineral deficiencies associated with opioid addiction have been well-described (160–165).”
From A Biopsychosocial Overview of the Opioid Crisis: Considering Nutrition and Gastrointestinal Health (2019) · cites this paper as [165]
Interest in reducing neuroinflammation in opioid recovery is beginning to receive considerable attention.
“Meanwhile, interest in reducing neuroinflammation in opioid recovery is beginning to receive considerable attention (165).”
From A Biopsychosocial Overview of the Opioid Crisis: Considering Nutrition and Gastrointestinal Health (2019) · cites this paper as [165]

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Authors: Mansouri, M. T., Naghizadeh, B., Ghorbanzadeh, B., Alboghobeish, S., Amirgholami, N., Houshmand, G., & Cauli, O.
Affiliations: Ahvaz Jundishapur University of Medical Sciences (IR)
Dezful University of Medical Sciences (IR)
Mazandaran University of Medical Sciences (IR)
Universitat de València (ES)
Corresponding author: Mansouri, Mohammad Taghi
Cauli, Omar
ORCID: Mansouri, Mohammad Taghi
Ghorbanzadeh, Behnam
Alboghobeish, Soheila
Cauli, Omar
Venue: Experimental Neurology
Publisher: Elsevier BV
Published: 2018-05
Volume: 303
Pages: 134-141
ISSN: 0014-4886 (ISSN-L)
DOI: 10.1016/j.expneurol.2018.02.009
OpenAlex: W2790624761
Cited by: 39
References: 74
Citations by year: 2026: 1 · 2025: 2 · 2024: 5 · 2023: 4 · 2022: 4 · 2021: 5 · 2020: 8 · 2019: 9 · 2018: 1
FWCI: 4.12
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Experimental Neurology (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
Health Sciences › Medicine › Anesthesiology and Pain Medicine › Pain Management and Opioid Use
Keywords: venlafaxine, morphine tolerance, opioid tolerance, neuroinflammation, nitric oxide, L-arginine, L-NAME, aminoguanidine, oxidative stress, inflammatory cytokines, brain-derived neurotrophic factor, glutathione peroxidase, malondialdehyde, antidepressants, anti-inflammatory activity, nociception
MeSH terms: Venlafaxine Hydrochloride, Analgesics, Opioid, Animals, Brain, Disease Models, Animal, Dose-Response Relationship, Drug, Enzyme Inhibitors, Glutathione Peroxidase, Male, Morphine, Morphine Dependence, Nitrites, Pain Measurement, Lipid Peroxidation, Signal Transduction, Cytokines, Oxidative Stress, Antidepressive Agents, Second-Generation, NG-Nitroarginine Methyl Ester, Mice

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Venlafaxine prevents morphine antinociceptive tolerance: the role of neuroinflammation and the l-arginine-nitric oxide pathway

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