Glioblastoma (GBM) is the most aggressive and lethal primary brain tumor, characterized by rapid proliferation, extensive vascularization, and resistance to conventional therapies. A feature of the GBM microenvironment is hypoxia, which activates a wide range of adaptive responses orchestrated mainly by the hypoxia-inducible factor (HIF). The Von Hippel–Lindau protein (pVHL) is a central regulator of HIF stability, inducing proteasomal degradation under physiological conditions. However, in GBM, the pVHL is frequently mutated or functionally inactivated by several mechanisms, including microRNA regulation, post-translational modifications, or degradation by specific E3 ubiquitin ligases. This loss of function results in persistent HIF activation, thereby enhancing the oncogenic and pro-angiogenic environment that contributes to the progression and aggressiveness of GBM. This review focuses on the multifaceted roles of the pVHL-HIF axis and proposes it as a key driver of GBM malignancy.

Endometriosis is a systemic, estrogen dependent neuroinflammatory-mediated disease affecting approximately 10-15% of women of reproductive age. Clinical manifestations include chronic pelvic pain (CPP), dysmenorrhea, dyspareunia, dyschezia, dysuria, and infertility. Endometriosis-associated pain is multifactorial and comprises overlapping nociceptive, neuropathic, and nociplastic pain phenotypes driven by persistent inflammation, neuroangiogenesis, peripheral nerve involvement, and central sensitization (CS). These mechanisms may sustain pain beyond lesion excision, highlighting the importance of pelvic nervous system (PNS) involvement. This narrative review examines the role of neuropelveology (NP) in endometriosis, focusing on pain mechanisms, diagnostic implications, and surgical decision making. NP integrates pelvic neuroanatomy and neurophysiology into structured neurological assessment, pain mapping, symptom localization, and nerve sparing surgery. Current evidence suggests that NP may complement conventional evaluation in selected patients with refractory pain, neuropathic symptoms, discordance between symptom severity and imaging findings, or suspected involvement of the sacral plexus or sciatic nerve. Recognizing distinct pain phenotypes may support individualized treatment planning by balancing lesion excision with neural preservation and identifying patients who may benefit from multidisciplinary pain management, rehabilitation, neurolysis, or neuromodulation. Although current evidence remains limited, NP should be considered a complementary framework rather than a replacement for established endometriosis management. Prospective multicenter studies using standardized diagnostic criteria and long-term functional outcomes are needed to define its clinical utility.

Endometriosis is a systemic, estrogen dependent neuroinflammatory-mediated disease affecting approximately 10–15% of women of reproductive age. Clinical manifestations include chronic pelvic pain (CPP), dysmenorrhea, dyspareunia, dyschezia, dysuria, and infertility. Endometriosis-associated pain is multifactorial and comprises overlapping nociceptive, neuropathic, and nociplastic pain phenotypes driven by persistent inflammation, neuroangiogenesis, peripheral nerve involvement, and central sensitization (CS). These mechanisms may sustain pain beyond lesion excision, highlighting the importance of pelvic nervous system (PNS) involvement. This narrative review examines the role of neuropelveology (NP) in endometriosis, focusing on pain mechanisms, diagnostic implications, and surgical decision making. NP integrates pelvic neuroanatomy and neurophysiology into structured neurological assessment, pain mapping, symptom localization, and nerve sparing surgery. Current evidence suggests that NP may complement conventional evaluation in selected patients with refractory pain, neuropathic symptoms, discordance between symptom severity and imaging findings, or suspected involvement of the sacral plexus or sciatic nerve. Recognizing distinct pain phenotypes may support individualized treatment planning by balancing lesion excision with neural preservation and identifying patients who may benefit from multidisciplinary pain management, rehabilitation, neurolysis, or neuromodulation. Although current evidence remains limited, NP should be considered a complementary framework rather than a replacement for established endometriosis management. Prospective multicenter studies using standardized diagnostic criteria and long-term functional outcomes are needed to define its clinical utility.