Search Results (41)

Background/Objectives: Cancer pain affects 55–95% of patients with advanced malignancy, representing a complex syndrome involving nociceptive, neuropathic and nociplastic mechanisms. Despite therapeutic advances, two-thirds of patients with metastatic cancer experience inadequate pain control. This scoping review synthesizes recent advances in cancer pain pathophysiology and management, focusing on molecular and cellular mechanisms, emerging pharmacological, interventional and technological therapies and key evidence gaps to inform future precision-based pain management strategies. Methods: Following PRISMA-ScR methodology, we searched PubMed, Embase, Scopus, and Web of Science for studies published between January 2022 and September 2025. After screening 3412 records, 278 studies were included and analyzed across different domains: biological mechanisms, pharmacological management, interventional and neuromodulatory approaches, radiotherapy developments, and digital health innovations. Results: Recent mechanistic research reveals cancer pain arises from tumor–neuron–immune crosstalk, with malignant cells secreting neurotrophic factors that promote axonal sprouting and nociceptor sensitization. Genetic polymorphisms and epigenetic modifications contribute to inter-individual pain variability. Management strategies are evolving toward multimodal precision medicine: NSAIDs and opioids remain foundational, complemented by adjuvant agents and interventional procedures including nerve blocks, intrathecal delivery, and neuromodulation (spinal cord and dorsal root ganglion stimulation). Stereotactic body radiotherapy demonstrates superior analgesic durability versus conventional approaches. Digital health innovations, such as mobile applications, remote monitoring, wearables, and AI-enabled predictive models, enable continuous assessment and personalized treatment optimization. Conclusions: Cancer pain management is transitioning toward mechanism-based precision medicine integrating biological insights, advanced interventional techniques, and digital technologies. However, implementation challenges persist, including limited randomized trials for interventional approaches, the incomplete external validation of AI tools, and digital health equity concerns. Future research must prioritize prospective controlled studies and equitable integration into routine care. Full article

Background/Objectives: Spinal cord stimulation (SCS) is an established therapy for chronic pain, but uncertainties remain regarding long-term real-world outcomes and the role of standardized selection pathways. This study aimed to evaluate real-world, longitudinal outcomes of SCS over 24 months within a structured clinical pathway, focusing on pain intensity, neuropathic symptoms, and health-related quality of life. Methods: A single-center, retrospective observational cohort study was conducted at the Fondazione Istituto G. Giglio (Cefalù, Italy). Data were drawn from the continuing, prospective institutional “SCS Pathway” and included consecutive patients implanted between May 2021 and September 2024. Eligible patients were ≥18 years of age with chronic pain refractory to conventional medical management. Outcomes included pain intensity (VAS, visual analog scale), neuropathic features (DN4, douleur neuropathique 4), and health-related quality of life (EQ-5D, EuroQol 5 Dimensions), assessed at baseline and 3, 6, 12, 18, and 24 months post-implantation. Multilevel models with full information maximum likelihood (FIML) were applied to repeated measures. Results: Seventy-six patients were included (mean age 67.3 ± 10.3 years; 39.5% female). The most frequent diagnoses were post-surgical pain syndrome (42.1%, 32/76) and chronic back and leg pain (40.8%, 31/76). 42.1% (32/76) had previous spine surgery, and 78.9% (60/76) reported neuropathic pain. Across 452 observations, mean VAS scores decreased from 7.9 ± 0.7 at baseline to 3.1 ± 1.1 at 3 months (61% reduction, p < 0.001), with sustained benefit at 24 months (4.5 ± 1.5; 43% reduction, p < 0.001). DN4 scores improved from 7.4 ± 0.8 to 3.2 ± 1.0 at 3 months (56% reduction, p < 0.001), with persistent decreases at 24 months (4.2 ± 1.2; 43% reduction, p < 0.001). EQ-5D improved from 22.8 ± 6.6 at baseline to 70.2 ± 10.6 at 3 months (increase of 208%, p < 0.001), with clinically meaningful gains sustained at 24 months (55.4 ± 13.7, increase of 143%, p < 0.001). Conclusions: In this real-world cohort, SCS therapy results in sustained, clinically significant improvements in pain, neuropathic symptoms, and quality of life. Findings highlight the value of structured selection and follow-up pathways. These data provide a benchmark for multicenter studies linking standardized referral frameworks to long-term, patient-centered outcomes. Full article

Introduction: Persistent Spinal Pain Syndrome Type 2 (PSPS-T2) is associated with changes in the brain’s pain processing. This is often due to problems with the body’s natural way of handling the pain management system. Exercise therapy, such as motor control and spinal stabilization, can help reduce pain and disability. However, exercise alone may not be sufficient. Approaches that consider both body mechanics and brain function are gaining popularity. Since brain changes play a role in muscle and bone problems, noninvasive brain stimulation (NIBS) is considered a helpful adjunctive treatment. Studies have shown that NIBS may help people with spinal pain and mood disorders. The aim of this study is to assess the impact of combining tDCS targeting the dorsolateral prefrontal cortex with spinal motor control exercises in patients diagnosed with PSPS-T2. This investigation is based on the hypothesis that such a combined intervention could result in a more significant reduction in disability. Methods/Materials: This randomized controlled trial (RCT) is structured as a double-blind, comparative, longitudinal design in accordance with the CONSORT guidelines. This RCT has been registered at ClinicalTrials.gov (NCT06969456). Forty-two participants diagnosed with PSPS-T2 will be randomized in a 1:1 ratio into two groups: tDCS + rehabilitation (E_tDCS) or sham tDCS + rehabilitation (E_SHAM). The intervention will use tDCS to deliver low-intensity direct current to modulate cortical excitability. The intervention will consist of 24 supervised sessions (2 per week, 60 min each) over 12 weeks. Neuromodulation and exercise protocols will be adapted to the intervention phases based on previous research. The sample size has been calculated using GPower^®, assuming an effect size of 0.81, α = 0.05, power = 0.95, and a 40% dropout rate. Data will be collected from October 2025 to January 2027. Impact Statement: This study integrates neurophysiological modulation via tDCS with targeted exercise therapy, presenting an innovative approach to enhance pain modulation, functional recovery, and cortical reorganization in patients with PSPT-2. This approach has the potential to inform future evidence-based strategies for neurorehabilitation and pain management. Full article

Background: Bertolotti syndrome describes a painful lumbosacral transitional vertebra (LSTV) with a pseudoarticulation between an enlarged lateral process of the caudal lumbar vertebra (L5) and ilium or sacrum. It often presents with chronic lower back pain with or without radiculopathy. The current literature emphasizes Bertolotti as a differential diagnosis in young adults. However, it is presumably underdiagnosed in middle-aged and older patients. Treatment ranges from conservative treatment with physiotherapy, infiltration, and radiofrequency ablation to surgical interventions. Case Description: In this case illustration, we present the diagnostic and therapeutic challenges in a 48-year-old female triathlete with persistent left gluteal pain caused by Bertolotti syndrome. When conservative treatment with physiotherapy, infiltrations, thermocoagulation, and radiofrequency ablation of the pseudoarticulation failed, microsurgical reduction of the hypertrophic transverse process was performed. This minimally invasive intervention achieved satisfactory pain relief of at least 70% one year after surgery, allowing the patient to resume her athletic activities. Conclusions: Bertolotti syndrome should be considered a potential differential diagnosis in patients of all ages. Since many patients endure years of misdiagnosis, adequate treatment is crucial upon diagnosis. If conservative measures fail, surgical treatment such as “processectomy” or spinal fusion should be evaluated. This case follows the CARE reporting guidelines. Full article

Background/Objectives: The co-existence of multiple compression sites on the same nerve can pose a clinical and diagnostic challenge, warranting a different treatment strategy. This so-called double crush syndrome (DCS) has mainly been investigated in the upper limb. Only a few studies have investigated DCS for the lower limb. In this article, a single-center illustrative clinical case series is presented, and current literature on L5 nerve root (NR) and concomitant common peroneal nerve (CPN) is reviewed. Methods: All patients presenting between 2019 and 2022 with L5 nerve root (NR) compression and, along their clinical courses, concomitant compression of the common peroneal nerve (CPN) at the fibular head were included. Information on clinical features, diagnostics and surgeries was obtained. The outcome was assessed at the last outpatient follow-up appointment. In addition, an extensive literature review has been conducted. Results: Fourteen patients were included with a mean follow-up of 6.8 months. The majority had pain (71%) or motor deficits (71%). Seven patients were referred for clinical and radiological L5 NR compression but were also found to have CPN compression; the other seven patients had persisting or recurrent symptoms after surgically or conservatively treated L5 NR compression, suggestive of additional peroneal neuropathy. All patients had CPN decompression at the fibular head, with successful results obtained in 93% of the patients. Pain of the lower leg improved in all patients, and dorsiflexion function improved in 78%. Conclusions: Concomitant L5 NR and CPN appear to occur more frequently than expected. Peroneal neuropathy can present simultaneously with L5 nerve radiculopathy or after surgically or conservatively treated L5 NR compression. Overlapping symptoms and variation in clinical presentations make it difficult to diagnose and, therefore, underrecognized. More awareness among treating physicians of this specific double crush syndrome is important to prevent any delay in treatment, in this case, a less invasive common peroneal nerve release at the fibular head, and to avoid unnecessary (additional) spinal surgery. Full article

Background/Objectives: Diagnosis of Persistent Spinal Pain Syndrome Type 2 (PSPS-T2) currently lacks objective biomarkers. Therefore, this retrospective study aimed to investigate differences in glucose metabolism in the axial musculoskeletal system in PSPS-T2 patients by means of [¹⁸F]FDG PET-CT imaging. Methods: Nine PSPS-T2 patients (five females, four males; mean age of 53 ± 4.82 years) and nine age- and gender-matched healthy controls (five females, four males; mean age of 53 ± 3.91 years) were included. For each participant, 24 regions of interest (ROIs) were manually drawn, including areas of the vertebral endplates, the intervertebral discs, and the psoas muscles. For each ROI, the mean standardized uptake values (SUVs) were assessed. Group differences were evaluated using repeated measures ANOVA with Bonferroni-adjusted post-hoc pairwise comparisons. Additionally, Pearson correlation analyses examined associations between SUV_mean values and the Numerical Rating Scale (NRS) pain scores. Results: Results demonstrated significantly higher SUV_mean values in healthy controls compared to PSPS-T2 patients, particularly at the superior endplates of L4 and S1, the intervertebral discs at L4-L5 and L5-S1, and the posterior endplates of L4 and L5. Although PSPS-T2 patients exhibited higher SUV_mean values than controls in the psoas muscle, these differences were not statistically significant. Additionally, no significant correlations were found between SUV_mean values and NRS pain scores, suggesting that metabolic activity alone does not directly reflect pain severity. Conclusions: Despite the limited sample size of this pilot study, the metabolic fingerprint of the axial musculoskeletal system was shown to be distinctly different in PSPS-T2 patients compared to healthy controls. This could lead to an improved understanding of PSPS-T2 pathophysiology and might open new doors for better diagnosis and treatment strategies. Full article

Background: Spinal cord stimulation (SCS) is applied for managing chronic intractable pain, but the factors predicting its effectiveness have not been extensively researched. Our study aimed to identify clinical variables that can predict the outcome of SCS. Methods: The electronic medical records of patients who received SCS for chronic intractable pain at two large tertiary teaching institutions in South Korea from 2008 to 2022 were reviewed. A successful outcome was characterized by attaining at least a 50% reduction in pain on the numerical rating scale (NRS) assessed at 6 months. Multivariable analysis was used to investigate the correlation between outcomes of SCS and clinical variables. Results: Of the 213 patients, 108 (50.7%) experienced successful outcomes at 6 months after SCS implantation. At 6 months, both the positive and negative outcome groups had significantly lower NRS pain scores than at baseline. Multivariable analysis revealed that male gender (p = 0.023) was an independent predictor of positive SCS outcomes; conversely, longer pain duration (p = 0.011) was a negative predictor. No significant adverse events associated with SCS were observed throughout the six-month follow-up duration. Conclusions: SCS could be an effective treatment for chronic intractable pain, including complex regional pain syndrome (CRPS) and persistent spinal pain syndrome (PSPS). More successful outcomes may be expected in male patients with a shorter duration of pain. Additional research is required to enhance patient selection processes and to identify clinical characteristics that contribute to improved long-term outcomes. Full article

Background/Objectives: Functional spinal instability from multifidus dysfunction has been proposed as a mechanism for chronic postsurgical pain. Prior studies reported structural impairments in the lumbar multifidus in patients with chronic low back pain, including a reduced cross-sectional area, muscle thickness, and increased fat infiltration. This preliminary report examined the prevalence of multifidus fat infiltration after Spinal Cord Stimulation (SCS), an established pain management technique. It also assessed inter-rater reliability in evaluating fat infiltration using MRI. Methods: The medical imaging data from four patients with Persistent Spinal Pain Syndrome Type II (PSPS II) treated with SCS were collected. Two independent operators performed the manual segmentation of the multifidus muscle on axial MRI images of the lumbar spine. The fat-to-muscle ratio was quantified and rated using a four-point classification system, categorizing multifidus fat infiltration as normal, mild, moderate, or severe. To assess the reliability of the manual segmentations, inter-rater reliability was determined. Results: The median fat-to-muscle ratio at the levels L2–L3 was 46.12 (Q1–Q3: 44.88–47.35). At the levels L3–L4, L4–L5, and L5–S1, the median values were 50.45 (Q1–Q3: 45.57–52.98), 52.11 (Q1–Q3: 48.81–52.80), and 52.84 (Q1–Q3: 49.09–56.39), respectively. An ICC value of one (95% CI from 0.999 to 1, p < 0.001) was found for inter-rater agreement on the muscle volume of the multifidus muscle. Conclusions: All the patients had moderate-to-severe fat infiltration of the multifidus muscle at each lumbar spinal level. Although time-consuming, the manual segmentation of the multifidus muscle in patients treated with SCS was feasible and yielded excellent inter-rater reliability when determining muscle volume. Future endeavors should focus on the automation of segmentation and classification. Full article

Background/Objectives: Neuroimaging biomarkers could offer more objective measures of the pain experience. This study investigated rT1/T2 maps of the brain as a novel biomarker for chronic pain in patients with central post-stroke pain (PSP) and persistent spinal pain syndrome type 2 (PSPS-II). Methods: Patients with PSP and PSPS-II were retrospectively included alongside healthy controls. Bias correction and intensity normalization were applied to the T1-weighted and T2-weighted images to generate the rT1/T2 maps of the brain. Subsequently, rT1/T2 maps were spatially correlated with neurotransmitter atlases derived from molecular imaging. Results: In total, 15 PSPS-II patients, 11 PSP patients, and 18 healthy controls were included. No significant differences between patient and control demographics were found. Significant decreases in rT1/T2 signal intensity (p < 0.001) were observed in the dorsal and medial part of the thalamus, left caudate nucleus, cuneus, superior frontal gyrus, and dorsal cervicomedullary junction in PSP patients. No significant changes were found in rT1/T2 signal intensity in PSPS-II patients. Significant correlations were found with CB1-, 5HT2a-, and mGluR5-receptor maps (pFDR = 0.003, 0.030, and 0.030, respectively) for the PSP patients and with CB1-, 5HT1a-, 5HT2a-, KappaOp-, and mGluR5-receptor maps (pFDR = 0.003, 0.002, 0.002, 0.003, and 0.002, respectively) in PSPS-II patients. Conclusions: These findings suggest that microstructural alterations occur in the thalamus, cuneus, and dorsal cervicomedullary junction in patients with PSP. The lack of significant findings in rT1/T2 in PSPS-II patients combined with the significant correlations with multiple neurotransmitter maps suggests varying degrees of microstructural deterioration in both chronic pain syndromes, although further research is warranted. Full article

Refractory angina pectoris (RAP) is a clinical syndrome characterized by persistent chest pain caused by myocardial ischemia that is unresponsive to optimal pharmacological therapy and revascularization procedures. Spinal cord stimulation (SCS) has emerged as a promising therapeutic option for managing RAP, offering significant symptom relief and improved quality of life. A systematic literature review was conducted to evaluate the clinical effectiveness, mechanisms of action, and safety profile of SCS in treating RAP. Comprehensive searches were performed in PubMed, Scopus, and Web of Science for studies published between 1990 and 2023. Of 328 articles identified, 6 met the inclusion and exclusion criteria for final analysis. The included studies consistently demonstrated that SCS significantly reduces the frequency of anginal episodes and nitroglycerin use while improving exercise capacity and quality of life. Proposed mechanisms include modulation of pain signals via the gate control theory, enhancement of autonomic balance, and redistribution of myocardial perfusion. Novel stimulation modalities, including high-frequency, Burst, and Differential Target Multiplexed (DTM), show potential advantages in enhancing patient comfort and clinical outcomes. Nevertheless, long-term studies are necessary to validate these findings and establish the comparative efficacy of these advanced technologies. SCS is a safe and effective therapy for patients with RAP who are unsuitable for surgical interventions. Innovations in neurostimulation, including closed-loop systems and personalized treatment strategies have the potential to further optimize outcomes. Rigorous clinical trials are needed to consolidate the role of SCS as a cornerstone therapy for the management of RAP. Full article

Background and Objectives: The International Society for Modulation defines persistent spinal pain syndrome type 2 (PSPS-type 2), formerly known as failed back surgery syndrome, as a condition where patients continue to experience pain or develop new pain following spinal surgery intended to alleviate back or lower-limb discomfort. PSPS-type 2 is characterized by pain and significant disability, affecting quality of life. Spinal cord stimulation has proven effective in treating this syndrome, although the role of psychological factors, such as pain catastrophizing and central sensitization, remain unclear. This study seeks to examine the potential connection between psychosocial responses and both functionality and pain perception in patients with persistent spinal pain syndrome type 2 who have undergone spinal cord stimulation treatment. Materials and Methods: A single-site, cross-sectional study was conducted on individuals diagnosed with persistent spinal pain syndrome type 2 who were receiving spinal cord stimulation. Study participants were required to meet specific eligibility criteria and were assessed for disability, pain perception, fear of movement, pain catastrophizing, and central sensitization. The spinal cord stimulation procedure involved the placement of electrodes at vertebral levels T8–T11 for precise pain control, with a particular focus on targeting the dorsal root ganglion to alleviate chronic pain. Results: Thirty-seven patients with persistent spinal pain syndrome type 2 have undergone spinal cord stimulation treatment for 4.68 ± 5.25 years. Clinical assessments indicated a pain perception score of 5.6 ± 1.96, Central Sensitization Inventory score of 42.08 ± 18.39, disability score of 37.62 ± 16.13, fear of movement score of 33.11 ± 8.76, and pain catastrophizing score of 28.43 ± 13.14. Finally, pain catastrophizing was significantly associated with pain perception (β = 0.075 and p = 0.008) and disability (β = 0.90 and p < 0.01). Conclusions: Catastrophizing plays a crucial role in pain perception and disability among patients with persistent spinal pain syndrome type 2 receiving spinal cord stimulation. Integrating psychological interventions may improve clinical outcomes for these patients. Full article

Background/Objectives: Over the last 20 years, spinal cord stimulation (SCS) has seen the development of various paresthesia-free paradigms. Recently, a novel modality has emerged (Fast-Acting Sub-perception Therapy, FAST) that engages the surrounding inhibition mechanism of action. We evaluated long-term, real-world outcomes of preferential FAST-SCS use in patients with chronic pain. Methods: In this multi-center, observational, consecutive case series, medical chart data from chronic pain patients preferentially using FAST-SCS (no exclusions) were retrospectively reviewed. Results: Data from 167 patients in 13 European centers were analyzed; 74% of patients suffered from persistent spine pain syndrome type 2 and 87% presented with low back and/or leg pain. At the last follow-up (mean 1.6 years), the numerical rating scale (NRS) overall pain score decreased by 5.1 ± 2.5 points versus baseline, from 8.0 ± 1.2 to 2.9 ± 2.2 (n = 167, p < 0.0001). 87% of patients reported ≥50% pain relief, and 55% were “high responders” with overall NRS pain scores ≤2/10. At the last follow-up, functional disability improved significantly (the Oswestry Disability Index reduced by 29.2 ± 21.5 points, n = 65, p < 0.0001) and patients had a significant gain in quality of life (EQ-5D-5L visual analog scale increased by 52.0 ± 26.9 points, n = 86, p < 0.0001). Results at the 2-year follow-up showed a sustained, substantial reduction in pain; 67% of patients were high responders and the NRS overall pain score decreased by 5.6 ± 2.4 versus baseline (n = 52, p < 0.0001). Conclusions: Our real-world outcomes suggest that in patients with chronic low back and/or leg pain, FAST-SCS therapy provided durable and profound pain relief and led to significant improvements in disability and quality of life. Full article

Background: Caloric vestibular stimulation (CVS) is a well-established neurological diagnostic technique that also induces many phenomenological modulations, including reductions in phantom limb pain (PLP), spinal cord injury pain (SCIP), and central post-stroke pain. Objective: We aimed to assess in a variety of persistent pain (PP) conditions (i) short-term pain modulation by CVS relative to a forehead ice pack cold-arousal control procedure and (ii) the duration and repeatability of CVS modulations. The tolerability of CVS was also assessed and has been reported separately. Methods: We conducted a convenience-based non-randomised single-blinded placebo-controlled study. Thirty-eight PP patients were assessed (PLP, n = 8; SCIP, n = 12; complex regional pain syndrome, CRPS, n = 14; non-specific PP, n = 4). Patients underwent 1–3 separate-day sessions of iced-water right-ear CVS. All but four also underwent the ice pack procedure. Analyses used patient-reported numerical rating scale pain intensity (NRS-PI) scores for pain and allodynia. Results: Across all groups, NRS-PI for pain was significantly lower within 30 min post-CVS than post-ice pack (p < 0.01). Average reductions were 24.8% (CVS) and 6.4% (ice pack). CRPS appeared most responsive to CVS, while PLP and SCIP responses were less than expected from previous reports. The strongest CVS pain reductions lasted hours to over three weeks. CVS also induced substantial reductions in allodynia in three of nine allodynic CRPS patients, lasting 24 h to 1 month. As reported elsewhere, only one patient experienced emesis and CVS was widely rated by patients as a tolerable PP management intervention. Conclusions: Although these results require interpretative caution, CVS was found to modulate pain relative to an ice pack control. CVS also modulated allodynia in some cases. CVS should be examined for pain management efficacy using randomised controlled trials. Full article

Critical limb ischemia (CLI) is the most severe form of peripheral arterial disease, significantly impacting quality of life, morbidity and mortality. Common complications include severe limb pain, walking difficulties, ulcerations and limb amputations. For cases of CLI where surgical or endovascular reconstruction is not possible or fails, spinal cord stimulation (SCS) may be a treatment option. Currently, SCS is primarily prescribed as a symptomatic treatment for painful symptoms. It is used to treat intractable pain arising from various disorders, such as neuropathic pain secondary to persistent spinal pain syndrome (PSPS) and painful diabetic neuropathy. Data regarding the effect of SCS in treating CLI are varied, with the mechanism of action of vasodilatation in the peripheral microcirculatory system not yet fully understood. This review focuses on the surgical technique, new modalities of SCS, the mechanisms of action of SCS in vascular diseases and the parameters for selecting CLI patients, along with the clinical outcomes and complications. SCS is a safe and effective surgical option in selected patients with CLI, where surgical or endovascular revascularization is not feasible. Full article

Bladder pain is a prominent symptom in Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS). We studied spinal mechanisms of bladder pain in mice using a model where repeated activation of intravesical Protease Activated Receptor-4 (PAR4) results in persistent bladder hyperalgesia (BHA) with little or no bladder inflammation. Persistent BHA is mediated by spinal macrophage migration inhibitory factor (MIF), and is associated with changes in lumbosacral proteomics. We investigated the contribution of individual spinal MIF receptors to persistent bladder pain as well as the spinal proteomics changes associated with relief of persistent BHA by spinal MIF antagonism. Female mice with persistent BHA received either intrathecal (i.t.) MIF monoclonal antibodies (mAb) or mouse IgG1 (isotype control antibody). MIF antagonism temporarily reversed persistent BHA (peak effect: 2 h), while control IgG1 had no effect. Moreover, i.t. antagonism of the MIF receptors CD74 and C-X-C chemokine receptor type 4 (CXCR4) partially reversed persistent BHA. For proteomics experiments, four separate groups of mice received either repeated intravesical scrambled peptide and sham i.t. injection (control, no pain group) or repeated intravesical PAR4 and: sham i.t.; isotype IgG1 i.t. (15 μg); or MIF mAb (15 μg). L6-S1 spinal segments were excised 2 h post-injection and examined for proteomics changes using LC-MS/MS. Unbiased proteomics analysis identified and relatively quantified 6739 proteins. We selected proteins that showed significant changes compared to control (no pain group) after intravesical PAR4 (sham or IgG i.t. treatment) and showed no significant change after i.t. MIF antagonism. Six proteins decreased during persistent BHA (V-set transmembrane domain-containing protein 2-like confirmed by immunohistochemistry), while two proteins increased. Spinal MIF antagonism reversed protein changes. Therefore, spinal MIF and MIF receptors mediate persistent BHA and changes in specific spinal proteins. These novel MIF-modulated spinal proteins represent possible new targets to disrupt spinal mechanisms that mediate persistent bladder pain. Full article