The global obesity pandemic has unveiled adipose tissue as a pivotal, active modulator of neurological health, intricately linking metabolic dysfunction to chronic pain and cognitive decline. This review synthesizes current evidence to propose a unified “neuro-metabo-inflammatory” model of the adipose-central nervous system (CNS) axis. We articulate a framework where, in pathological states such as obesity, dysfunctional adipose tissue releases a milieu of factors—including adipokines, lipids, and extracellular vesicles—that propagate peripheral and central neuroinflammation, disrupt blood–brain barrier integrity, and impair synaptic plasticity. These processes converge to drive pain sensitization and cognitive deficits. Critically, we evaluate the clinical evidence linking visceral adiposity to multisite chronic pain and accelerated cognitive impairment, while highlighting sexually dimorphic pathways. The review moves beyond cataloging findings to prioritize the most robust mechanisms, assess evidence quality, and identify key translational gaps. We conclude by discussing emerging therapeutic strategies targeting this axis and proposing precise directions for future research to disentangle the complex temporal and spatial dynamics of adipose–CNS communication.

Background: Neuropathic pain (NP) frequently co‐occurs with depression (DP), exhibiting complex pathogenesis and limited clinical treatment options. This study aims to investigate the efficacy of Eupalinolide B (EB) in alleviating NP co‐occurring with DP and its potential molecular mechanisms. Methods: Combining network pharmacology, molecular docking, and molecular dynamics simulations to screen potential targets for EB, validated through transcriptomic data. Using a sciatic nerve branch‐preserving injury (SNI) mouse model, we assessed pain and depression‐like behaviors through von Frey testing, hot plate testing, tail suspension testing, forced swimming testing, and open field testing. Concurrently, Western blotting, immunofluorescence, and Nissl staining were employed to analyze relevant molecules and neuropathological alterations. Results: Network pharmacology and bioinformatics analysis identified EGFR, PTGS2, and JUN as the key targets for EB in treating NP combined with DP. Behavioral studies showed that 20 mg/kg of EB significantly alleviated pain in SNI mice and improved depressive‐like behaviors. Mechanism research indicated that EB downregulated the expression of EGFR and PTGS2, inhibited the activation of microglia and astrocytes, and reduced neuronal damage. Additionally, EB could upregulate the expression of synaptic proteins (PSD95, SYN1, and BDNF) in the hippocampus. Conclusion: EB alleviates neuroinflammation by reducing EGFR and PTGS2 protein expression, modulates synaptic plasticity, and improves pain‐depression comorbidity. EB may represent a promising therapeutic approach for pain‐related depression.

Rationale: Posterior percutaneous endoscopic cervical discectomy (P-PECD) is a minimally invasive procedure for cervical spine disorders. Although it is associated with less surgical trauma and faster postoperative recovery, serious perioperative thromboembolic complications may still occur. Patient concerns: A 65-year-old woman with cervical disc herniation, right upper limb pain, and multiple comorbidities underwent posterior percutaneous endoscopic cervical discectomy after unsuccessful conservative treatment. On the 2nd postoperative day, she developed dizziness and decreased oxygen saturation. On the 3rd postoperative day, she complained of chest tightness. Diagnoses: Laboratory testing revealed a markedly elevated plasma D-dimer level. Venous color Doppler ultrasound of both lower limbs demonstrated thrombosis in the bilateral calf muscular veins, and computed tomography pulmonary angiography confirmed multiple pulmonary emboli. Interventions: The patient received oxygen therapy, continuous cardiorespiratory monitoring, anticoagulation with low-molecular-weight heparin, and other supportive treatments. She was transferred to the intensive care unit for further monitoring and management. Outcomes: The patient’s respiratory and circulatory status gradually stabilized, and her chest tightness and dizziness resolved. She was subsequently transferred back to the pain ward and discharged in stable condition. Lessons: This case highlights that minimally invasive spinal surgery does not eliminate the risk of perioperative venous thromboembolism. Comprehensive preoperative thrombotic risk assessment, individualized perioperative management of antithrombotic therapy, appropriate thromboprophylaxis, early mobilization, and timely recognition and treatment of suspected APE are important for improving perioperative safety.