Exploring venlafaxine effects on chronic vulvar pain: Changes in mood and pain regulation networks

Yaseen Awad-Igbaria, Saher Abu-Ata, Yara Nakhleh-Francis, Lior Lowenstein, Karen Ginat, Jacob Bornstein, Eilam Palzur, Alon Shamir

Research output: Contribution to journalArticlepeer-review


The etiology of idiopathic pain conditions, such as Provoked vulvodynia (PV), is multifactorial. The efficiency of venlafaxine, serotonin-noradrenaline reuptake inhibitor (SNRIs) in modulating vulvar pain led to the hypothesis that PV might involve central mechanisms. Here, we investigate whether vulvar pain is associated with gene-expression changes in mood, stress and pain systems, including amygdala (Amg), medial prefrontal cortex (mPFC), and periaqueductal gray matter (PAG). Additionally, we examined the analgesic and anxiolytic effects of venlafaxine. We found that the development of chronic vulvar pain in an animal model of PV is associated by overexpression of genes related to neuronal-activity and neuroinflammation in the Amg, mPFC, and PAG. Additionally, changes in the expression of GABA and serotonin synthesis, and reuptake were noted in the Amg and mPFC. Unsurprisingly, anxiety-like behavior and emotional-disorder were observed in rats with chronic vulvar pain. Nevertheless, treatment with venlafaxine (37.5 mg/kg) for one month significantly improves the vulvar hypersensitivity, as well as reduces the anxiety level. More critically, the long-term gene expression adaptation in serotonin receptor and synthesis, GABA synthesis, neuroplasticity, and neuroinflammation in the Amg, mPFC, and PAG, were modulated by venlafaxine in rats with vulvar pain. Our findings suggest that vulvar hypersensitivity induced by inflammation might associated with gene expression changes in brain areas that are involved in mood, stress and pain regulation. These changes probably play a role in central sensitization, and anxiety. Strikingly, enhancing the activity of serotonin and noradrenaline via venlafaxine treatment in rats with vulvar pain induces analgesic and anxiolytic effects.

Original languageEnglish
Article number109788
StatePublished - 1 Feb 2024

Bibliographical note

Publisher Copyright:
© 2023 Elsevier Ltd


The current research was supported by a grant from the National Institute of Psychobiology in Israel (NIPI) Grant (Research No. 231-19-20B ) granted to Alon Shamir, Psychobiology Research Laboratory, Mazor Mental Health Center, Akko, Israel.

FundersFunder number
Alon Shamir
Mazor Mental Health Center
National Institute of Psychobiology in Israel231-19-20B
Psychobiology Research Laboratory


    • Anxiety
    • Central sensitization
    • Chronic pain
    • Neuronal adaptation


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