Mechanisms linking chronic prostatitis/chronic pelvic pain syndrome with anxiety and depression: a scoping review

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a prevalent and clinically heterogeneous urological disorder characterized by persistent pelvic pain, lower urinary tract symptoms, and significant impairment in quality of life. Beyond its urological manifestations, CP/CPPS is frequently associated with psychiatric comorbidities, particularly anxiety and depression, suggesting that its pathophysiology extends beyond the peripheral urogenital system and involves complex central and systemic mechanisms. This scoping review maps and synthesizes literature on CP/CPPS-related neurobiological, neuroimmune, neuroendocrine, and psychosocial mechanisms, integrating preclinical, clinical, and neuroimaging evidence to build a framework linking chronic pelvic pain with affective disorders.

A scoping review methodology was used to identify and synthesize literature on CP/CPPS and its psychiatric comorbidities. A structured search was performed in PubMed, Scopus, and Web of Science using keywords such as ‘chronic prostatitis,’ ‘chronic pelvic pain syndrome,’ ‘anxiety,’ ‘depression,’ ‘neuroinflammation,’ ‘HPA axis,’ and ‘central sensitization.’ Eligible studies included preclinical, clinical, neuroimaging, and mechanistics, and were categorized into neuroinflammatory, neuroendocrine, neurotransmitter-related, and psychosocial domains. The review focused on studies published in English from the past decade to ensure up-to-date evidence synthesis.

The literature consistently demonstrates that CP/CPPS is associated with maladaptive neuroplastic changes within central pain–emotion networks, with neuroimaging studies revealing structural and functional alterations in key brain regions involved in pain processing and emotional regulation, including the anterior cingulate cortex, insula, amygdala, hippocampus, and prefrontal cortex, suggesting disrupted connectivity and impaired top-down modulation of nociceptive and affective processing.At the molecular level, neuroinflammation emerges as a central mechanism. Activation of microglia and astrocytes, together with increased levels of pro-inflammatory cytokines such as interleukin-1β, interleukin-6, and tumor necrosis factor-α, contributes to sustained neuroimmune activation and central sensitization. These processes increase neuronal excitability and promote persistent pain states while simultaneously affecting mood-regulating circuits.Dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis represents another key pathway linking chronic stress with pain and psychiatric symptoms. Altered cortisol dynamics contribute to limbic system remodeling and impaired emotional regulation. In parallel, imbalances in serotonergic, dopaminergic, glutamatergic, and GABAergic neurotransmitter systems further amplify nociceptive transmission and affective disturbances.Endocrine alterations, including reduced testosterone levels and disrupted melatonin signaling, may further exacerbate neurochemical instability and circadian dysregulation. Additionally, activation of the tryptophan-kynurenine pathway under inflammatory conditions reduces serotonin availability while increasing neuroactive metabolites associated with neurotoxicity and mood dysregulation.Psychosocial factors such as chronic stress, pain catastrophizing, sleep disturbances, sexual dysfunction, and reduced social support interact bidirectionally with biological mechanisms. These interactions amplify central sensitization and reinforce maladaptive pain emotion loops.

The synthesized literature suggests that CP/CPPS should be conceptualized as an integrated peripheral and central dysfunction rather than a purely urological condition. The convergence of neuroimmune activation, neuroendocrine dysregulation, neurotransmitter imbalance, and psychosocial stressors creates a self-perpetuating cycle linking chronic pain with anxiety and depression. Collectively, this scoping review integrates heterogeneous evidence across disciplines to provide a unified mechanistic framework for CP/CPPS. Future research should focus on longitudinal, translational, and mechanistic studies to better stratify patient phenotypes and develop targeted multimodal therapeutic strategies addressing both somatic and psychiatric dimensions of the disease.

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