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<p>Male sexual dysfunction (MSD) is a multifactorial condition in which traditional models focusing on vascular, endocrine, and psychogenic factors are insufficient. Emerging evidence highlights dysregulated crosstalk between the nervous and immune systems—the neuroimmune axis—as a potential unifying pathological substrate. This review synthesizes fragmented yet compelling evidence linking neural injury, chronic inflammation (both systemic and neurogenic), and immune dysregulation to the pathogenesis of MSD. We propose a novel integrative framework in which disruption of the neuro-immune axis serves as a convergent pathway for diverse etiologies, ranging from diabetic neuropathy to chronic pelvic pain. Central to this framework is the concept that immune-mediated processes exacerbate neural and vascular damage, creating a self-perpetuating cycle of dysfunction. Building on this mechanistic perspective, we explore the translational potential of neurosurgical and neuromodulatory strategies—such as sacral neuromodulation and vagus nerve stimulation—to restore neuroimmune homeostasis. Although direct clinical evidence in MSD remains limited, insights from related fields, including chronic pain and autoimmune disorders, provide a strong rationale for further investigation. This review aims to bridge mechanistic insights with therapeutic innovation, charting a course for future research into precision neuromodulation as a promising frontier for refractory MSD.</p>

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Targeting the neuro–immune axis: immunological mechanisms and therapeutic strategies in male sexual dysfunction

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月20日

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  • Zheng Hu,
  • Jun Luo,
  • Jianyun Lou,
  • Juntao Deng,
  • Zi tao Gong,
  • Jinming Chen

摘要

Male sexual dysfunction (MSD) is a multifactorial condition in which traditional models focusing on vascular, endocrine, and psychogenic factors are insufficient. Emerging evidence highlights dysregulated crosstalk between the nervous and immune systems—the neuroimmune axis—as a potential unifying pathological substrate. This review synthesizes fragmented yet compelling evidence linking neural injury, chronic inflammation (both systemic and neurogenic), and immune dysregulation to the pathogenesis of MSD. We propose a novel integrative framework in which disruption of the neuro-immune axis serves as a convergent pathway for diverse etiologies, ranging from diabetic neuropathy to chronic pelvic pain. Central to this framework is the concept that immune-mediated processes exacerbate neural and vascular damage, creating a self-perpetuating cycle of dysfunction. Building on this mechanistic perspective, we explore the translational potential of neurosurgical and neuromodulatory strategies—such as sacral neuromodulation and vagus nerve stimulation—to restore neuroimmune homeostasis. Although direct clinical evidence in MSD remains limited, insights from related fields, including chronic pain and autoimmune disorders, provide a strong rationale for further investigation. This review aims to bridge mechanistic insights with therapeutic innovation, charting a course for future research into precision neuromodulation as a promising frontier for refractory MSD.