Chronic low back pain encompasses heterogeneous mechanical, neuropathic, nociplastic, and myofascial presentations that may reflect distinct neuroimmune mechanisms. We synthesized evidence linking these phenotypes to measurable biological features and clinically relevant treatment strategies. We conducted a structured literature search of MEDLINE, Scopus, Web of Science, and the Cochrane Central Register of Controlled Trials for studies published from January 2005 through January 2025. Systematic reviews, randomized controlled trials, and mechanistic studies addressing neuroinflammation, glial activation, central sensitization, biomarkers, or imaging were organized according to four clinically relevant pain phenotypes and translational readiness. Neuroimmune findings differed across axial mechanical, radicular neuropathic, nociplastic, and myofascial pain. Imaging of the 18-kDa translocator protein demonstrated phenotype-associated neuroinflammatory patterns, whereas shear wave elastography provided an objective measure of myofascial trigger-point stiffness. Combining inflammatory biomarkers with psychosocial characteristics improved chronic pain prediction, with reported areas under the receiver operating characteristic curve ranging from 0.69 to 0.92. Evidence also supported phenotype-aligned approaches including targeted rehabilitation, ultrasound-guided dry needling, dorsal root ganglion stimulation, and spinal cord stimulation. However, biomarker validation, imaging standardization, and clinical availability varied substantially. Neuroimmune phenotyping provides a framework for connecting pain mechanisms with diagnostic and therapeutic strategies in chronic low back pain. Shear wave elastography and selected inflammatory measures appear closest to clinical implementation, while advanced neuroimaging and multi-omic approaches remain investigational. Phenotype-enriched prospective trials are needed before routine precision-guided management can be established.
Fascial plane blocks (FPBs) are increasingly used in perioperative and pain medicine, but their clinical role remains difficult to define because mechanisms, nomenclature, and evidence quality vary across techniques and indications. Recent anatomical and clinical literature supports a shift away from viewing fascia as a passive conduit. Deep fascia is innervated, mechanically active, and organized into communicating compartments that may influence injectate spread and analgesia. Established techniques such as erector spinae plane, transversus abdominis plane, quadratus lumborum, pectoral plane, and serratus anterior plane blocks provide useful but indication-specific perioperative benefits. Comparative evidence is more nuanced when FPBs are tested against paravertebral or epidural techniques. Emerging posterior cervical and periscapular multitarget approaches are anatomically plausible but are supported only by a seven-patient uncontrolled series, technical or anatomical descriptions, and small retrospective uncontrolled studies; they should therefore be regarded as hypothesis-generating rather than practice-changing. Large-volume dosing and cumulative systemic local anesthetic exposure remain important safety considerations. FPBs should be used as anatomy-guided, indication-specific interventions rather than as a uniform class of interchangeable blocks. Emerging multitarget strategies are not yet established clinical recommendations. Future work should prioritize standardized nomenclature, dose discipline, comparative trials, and patient-centered outcomes.
Pain and fatigue are highly prevalent in neuromuscular (NM) diseases, including motor neuron, peripheral nerve, junctional, and myopathic pathologies. Their multifactorial pain mechanisms as neuropathic, nociceptive, and mixed often remain resistant to conventional pharmacologic and rehabilitative strategies. The long-term use of opioids carries significant adverse effects. Given these limitations, neuromodulation offers a non-pharmacologic approach to address pain and functional impairment in neuromuscular diseases. This narrative review synthesizes existing evidence and biological rationale for neuromodulation in NM disorders, summarizing prior and ongoing research and outlining future directions for clinical applications. A targeted literature search was performed across PubMed, and ClinicalTrials.gov through October 2025 for human studies using invasive or non-invasive neuromodulation. transcranial direct-current stimulation (tDCS), repetitive transcranial magnetic stimulation (rTMS), spinal cord stimulation (SCS), dorsal root ganglion (DRG) stimulation, peripheral nerve stimulation (PNS), vagus nerve stimulation (VNS), and trigeminal nerve stimulation (TNS) are searched for NM diseases. Eligible studies involved patients with NM diseases reporting pain, fatigue, or functional outcomes. Data were qualitatively synthesized by disease category and stimulation modality, and ongoing clinical trials were summarized. The available literature supports a biologically plausible and clinically promising role for neuromodulation in selected neuromuscular pain phenotypes, particularly where neuropathic mechanisms predominate. However, the evidence base remains fragmented, with limited disease specific trials and substantial heterogeneity in patient populations, stimulation parameters, and reported endpoints. These limitations currently prevent definitive conclusions about efficacy or routine clinical applicability. Neuromodulation offers an alternative, non-drug option to help relieve pain and fatigue in people with neuromuscular disorders. By targeting maladaptive excitability, central sensitization, and neuro-immune pathways, it holds potential to complement disease-modifying and rehabilitative strategies. However, evidence remains preliminary; standardized multicenter trials, biomarker-guided stratification, and integrative approaches are needed to define efficacy and optimize clinical translation.
Regenerative approaches for treating spinal pain hold great clinical promise but have the potential to disrupt healthcare upending the cost paradigm of pharmacologic care or interventional procedures. Regenerative approaches have higher upfront costs but may offer long-lasting, even curative benefits. In today’s healthcare system, it is important to understand the cost-effectiveness of regenerative approaches using mesenchymal stem cells (MSC), platelet-rich plasma (PRP), and other biologics. This narrative review explored the costs of these procedures for treating spinal pain, but since this specific indication is not currently approved for clinical use in the United States, cost data were sparse. This study was based on a narrative review and data obtained from the literature and available to the authors from a scientific session. While regenerative medicine is approved for certain indications, it has not yet been approved for use to treat painful spinal conditions, although there is evidence that it is a safe and effective procedure in this setting. In fact, PRP approaches to other musculoskeletal painful conditions are approved and increasing, according to Medicare. When compared to fusion surgery, MSC treatment of discogenic disease cost approximately 11,000 in the United States compared to two years of epidural spinal injections costing approximately900 each; the regenerative approaches offered better pain reduction (66
This review provides the reader with an up-to-date summary of the U.S. regulatory framework as it relates to regenerative medicine therapies used in pain management. This includes relevant historical background, legal discussion, prevailing evidence for the discussed therapies, and expert opinion on potential pathways forward that promote safety alongside innovation. Recent evidence in the regenerative medicine space supports the use of platelet rich plasma (PRP) for knee osteoarthritis, although findings are not uniform, with more limited data for bone marrow aspirate concentrate (BMAC) and adipose-derived products such as stromal vascular fraction (SVF). Perinatal tissue and exosomes show potential with early preclinical work. We gain valuable insight from warning notices and court rulings into how the FDA interprets guidance surrounding these therapies. With continued use and commercialization of regenerative medicine products for pain management, it is important to understand the regulatory aspects of these different therapies and how it may impact the day to day.
Low back pain (LBP) is a leading cause of disability worldwide, and its chronic forms—discogenic low back pain (DLBP) and vertebrogenic low back pain (VLBP)—remain difficult to diagnose and treat precisely. This review aims to clarify the anatomical and neurophysiological roles of the sinuvertebral nerve (SVN) and basivertebral nerve (BVN) in chronic LBP and to examine their implications for targeted diagnosis and treatment. Recent advances in neuroanatomy and imaging have shown that the SVN primarily mediates pain from intervertebral disc pathology, whereas the BVN is closely associated with vertebral endplate and marrow changes, particularly Modic changes. These two nerves are anatomically and functionally linked and together form a “vertebral-disc sensory unit.” Emerging evidence supports nerve-targeted interventions, including sinuvertebral and basivertebral nerve radiofrequency ablation, which can improve pain relief and functional outcomes in carefully selected patients. Functional and molecular imaging techniques are also expanding the ability to identify pain-generating structures more precisely. The SVN and BVN are key neural pathways in the pathogenesis of chronic LBP and represent important targets for precision diagnosis and treatment. Recognizing the vertebral-disc sensory unit provides a more integrated understanding of DLBP and VLBP. A better anatomical, functional, and imaging-based characterization of these nerves may improve patient selection and clinical outcomes for nerve-targeted therapies.
Hidradenitis suppurativa (HS) is an extremely painful skin condition with both nociceptive and neuropathic components. Biologics may offer superior neuropathic pain relief and impede worsening of this disease compared to other treatments. Of the three currently FDA-approved biologics (adalimumab, bimekizumab, and secukinumab), bimekizumab shows the largest absolute reduction in skin pain and the earliest onset of pain improvement. This review explores the pathophysiology and causes of neuropathic pain development in HS, highlights current FDA-approved and emerging biologics for its management, and raises awareness of neuropathic pain in HS. Clinical trial data assessing pain are unstandardized, and further elucidation of pain outcomes using standardized assessments of neuropathic pain is crucial for determining whether biologics targeting mediators that drive neuropathic pain development are effective in treating this aspect of HS.
Single-injection peripheral nerve blocks (PNBs) provide excellent perioperative analgesia in children but are limited by finite duration. Pediatric populations were excluded from the major adult adjunct reviews. This narrative review synthesizes the evidence for adjuncts added to local anesthetics for single-injection PNBs and caudal blocks in patients aged 0 to 18 years, including dexamethasone, dexmedetomidine, clonidine, conventional opioids, buprenorphine, magnesium sulfate, midazolam, ketamine, neostigmine, tramadol, nalbuphine, and epinephrine. Across 58 studies, dexmedetomidine (0.5 to 1 mcg/kg) and dexamethasone (0.1 mg/kg perineural) were the best-supported agents, each roughly doubling analgesic duration with acceptable safety. Two network meta-analyses ranked neostigmine highest for caudal duration, but its postoperative nausea and vomiting burden limits use. Clonidine has the longest safety record. Ketamine and midazolam show robust caudal efficacy but unresolved neurotoxicity concerns. Nalbuphine and buprenorphine are promising but under-studied. Tramadol carries pediatric regulatory restrictions, while epinephrine and conventional opioids add little. Dexmedetomidine and dexamethasone are the preferred adjuncts in pediatric regional anesthesia. Adult evidence should not be extrapolated directly given developmental pharmacology and pediatric-specific safety considerations. Prospective trials in true pediatric PNBs and pediatric rebound-pain studies remain the critical evidence gaps.
Headaches are a common chief complaint and a significant contributor to growing healthcare costs. Headaches are broadly categorized as primary or secondary, the latter indicating that they are a symptom of an underlying medical condition. Genetic vasculopathies are a heterogeneous cause of secondary headache recognized by the International Classification of Headache Disorders 3rd edition, with limited but growing literature. This review aims to describe specific genetic vasculopathies, outline the pathophysiology of headaches caused by genetic vasculopathies, and summarize diagnostic and treatment strategies. The most reported headache in genetic vasculopathies is migraine with or without aura, though headache phenotypes vary widely, as do the extra-central nervous system and systemic manifestations. Treatment is largely supportive, including focused headache management based on phenotype. Several widely used preventive agents warrant careful risk-benefit consideration due to side effect profiles that may be particularly relevant in this patient population. Genetic vasculopathies are a clinically significant category of secondary headaches that are recognized in the International Classification of Headache Disorders 3rd edition. As our understanding of genetic vasculopathies grows, so does the need for high-quality research investigating the diagnosis and management of secondary headaches as well as their underlying conditions.
This review provides an overview of the pharmacodynamics and pharmacokinetics of buprenorphine followed by a review of the published research on the perioperative use of buprenorphine for acute postoperative pain, and analgesia management in patients already on buprenorphine. Current evidence comparing buprenorphine with full opioid agonists is heterogeneous, showing either modest superiority or comparable analgesic efficacy, with a reduced incidence of certain adverse effects such as respiratory depression. Despite concerns that its high receptor affinity may limit the efficacy of additional opioids, buprenorphine can be safely combined with other opioid agonists for breakthrough and perioperative pain. Perioperative management requires an individualized, interdisciplinary approach, taking into account patient-specific risk factors. Multimodal analgesia—including regional techniques, non-opioid medications, adjunctive agents, and nonpharmacological strategies—forms the cornerstone of effective perioperative pain control. A structured postoperative plan with dose adjustment, coordinated follow-up, and collaboration with outpatient prescribers is critical. Early involvement of the Acute Pain Services team could be beneficial.
Lumbar spinal stenosis (LSS) is a common and disabling condition in older adults, and current treatment options leave a therapeutic gap between conservative management and open surgical decompression. Minimally invasive lumbar decompression (MILD) is a percutaneous, image-guided procedure that targets the hypertrophic ligamentum flavum as a primary driver of central canal narrowing. This systematic review evaluates the effectiveness and safety of MILD for the treatment of LSS. A systematic search of MEDLINE, Embase, Cochrane CENTRAL, and Web of Science was conducted for studies published between January 2016 and the first quarter of 2026. Studies were included if they enrolled adults with LSS who underwent the MILD procedure and reported validated clinical outcomes, such as the Visual Analog Scale, Numeric Rating Scale, Oswestry Disability Index, or Zurich Claudication Questionnaire. Sixteen publications representing 11 unique studies, including two randomized controlled trials and nine observational studies, met the inclusion criteria. Study quality was assessed using the Newcastle Ottawa Scale. Across the included studies, MILD was associated with consistent improvements in pain and disability compared with baseline and comparator treatments. In the MiDAS ENCORE trial, MILD produced significantly greater reductions in pain and disability than epidural steroid injections at 6 months. The MOTION trial demonstrated sustained improvements in pain, disability, and walking tolerance through three years compared with conventional medical management. Observational studies supported these findings and reported low rates of subsequent surgical intervention, generally at or under 12
Obesity is highly prevalent among patients with chronic musculoskeletal pain and is associated with low back pain, knee osteoarthritis, reduced mobility, and poorer functional outcomes. Glucagon-like peptide-1 (GLP-1) receptor agonists and related therapies have transformed obesity medicine and may become more relevant to pain medicine specialists. This narrative review examines whether GLP-1-based medications should be considered within pain practice, particularly for obesity-associated low back pain and knee osteoarthritis. Chronic pain impacts a substantial portion of adults, while low back pain and osteoarthritis remain leading causes of disability worldwide. Obesity is associated with low back pain and knee osteoarthritis, and weight reduction has been shown to improve pain and function in these conditions. GLP-1-based therapies can produce clinically meaningful weight loss in patients with obesity and chronic pain. Literature also suggests possible anti-inflammatory and chondroprotective effects relevant to pain. GLP-1-based medications should not be viewed as primary analgesics or replacements for standard pain evaluation, rehabilitation, pharmacologic care, or interventional treatment. However, they are reasonable to consider as part of comprehensive pain management in patients with obesity when excess weight plausibly contributes to chronic pain, impaired mobility, or reduced rehabilitation tolerance. Pain physicians familiar and comfortable with obesity pharmacotherapy may consider prescribing within appropriate indications and safety parameters. Alternatively, referral to obesity medicine, endocrinology, primary care, or another experienced clinician is appropriate.
Spine centers are common, but no standardized regulations govern their designation. Existing certifications are issued by multiple independent organizations and are not necessarily equivalent, while many centers remain non-accredited. Consequently, centers may vary in qualifications, quality of care, and services. This study examined and compared the defining characteristics of spine centers in Northeast America. A total of 194 spine centers were identified and compared based on accreditation, services, provider numbers, and proximity to metropolitan areas. Accreditation requirements from The Joint Commission (TJC), Det Norske Veritas (DNV), Aetna, and Blue Cross Blue Shield (BCBS) were analyzed. While substantial overlap existed, Aetna and BCBS largely built upon TJC standards, whereas DNV requirements differed, and exact criteria varied across organizations. Overall, 56
To provide a working definition of underserved populations in headache medicine for use in clinical and research settings. Prior research has identified disparities in headache care access, disease prevalence and burden in US populations by geographic location, poverty or disability status and for members of racial, ethnic or sexual and gender minority groups, or vulnerable groups such as new migrants. Research studies typically exclude other populations (pediatric, geriatric and pregnant/breastfeeding), which may limit the quality of headache care they receive. We propose that underserved populations in headache medicine is broadly defined as those facing barriers in access to headache care – specifically, individuals living in rural or geographically underserved areas, who are uninsured, underinsured or living in poverty, with disabilities, from historically marginalized racial/ethnic groups, who are LGBTQIA+, or vulnerable groups such as new migrants, asylum seekers and those with an undocumented status.
To critically reevaluate the role of phenol neurolysis in the management of refractory chronic non-cancer pain, focusing on mechanisms of action, formulations, clinical indications, procedural techniques, therapeutic efficacy, safety profile, economic considerations, and its relevance in the era of modern interventional pain therapies. Emerging evidence suggests that phenol neurolysis may provide meaningful analgesia and functional improvement in selected patients with refractory non-cancer pain, including spasticity, trigeminal neuralgia, osteoarthritis, coccydynia, and sympathetically maintained pain. However, available studies remain limited, heterogeneous, and largely observational, with substantial variability in concentrations, indications, and techniques. The overall quality of evidence is predominantly low to moderate. Despite declining use in contemporary practice, phenol neurolysis remains a potentially valuable option in selected clinical scenarios, particularly in resource-constrained settings. Significant knowledge gaps and lack of procedural standardization underscore the need for high-quality prospective research to better define its role in modern pain management.
Post-craniotomy headache (PCH) is a common complication following neurosurgery, yet there remains limited consensus regarding the mechanism, classification, and optimal management. This review summarizes the current literature and highlights recent trends in procedural therapies. PCH occurs in approximately 60–70
Acute postsurgical pain (APSP) and chronic postsurgical pain (CPSP) remain prevalent and insufficiently resolved challenges in perioperative medicine. This narrative review summarizes the current state of knowledge regarding personalized pain prediction, examines existing prognostic models and their limitations, and identifies the conceptual and methodological developments most likely to advance the field toward genuine individual prediction. Individual predictors, whether clinical, psychological, psychophysical, or surgical in nature, are, on their own, insufficiently informative to enable individual risk stratification. Existing multivariate prognostic models demonstrate at best moderate discriminatory power and are consistently rated as having a high risk of bias. To date, no externally validated predictive model exists for either outcome. Transitional Pain Services (TPS) and Shared Decision Making (SDM) represent promising organizational and communicative frameworks for translating risk stratification into clinical practice, although controlled trial evidence remains limited. Emerging approaches, including multidomain biosignatures, machine learning-based integration, and standardized outcome definitions, offer a particularly promising path toward genuinely personalized perioperative pain management. Personalizing perioperative pain prediction will require moving beyond individual risk factors toward the multidomain integration of biological, psychophysical, and psychosocial variables. Artificial intelligence could prove to be a catalyst for this integration, but the crucial step is conceptual in nature: recognizing postsurgical pain as a network phenomenon and establishing and implementing the clinical infrastructure needed to act on this insight.
Platelet Rich Plasma (PRP) is a regenerative medicine technique utilized across various fields of medicine. Utilizing components of a patient’s own blood, autologous applications of enriched biologic components including growth factors are thought to promote the healing process in various disease states. This modality has recently seen an expansion in various fields for novel applications. In pain medicine, this has seen similar growth for treatment of lumbar spine disease. Though this advancement is in its nascency, here we provide a narrative review to discuss the history and usage of PRP for the lumbar spine. PRP has been used in the spine for various purposes including adjuncts for surgical fusion and treatment for pain conditions such as facetogenic back pain, radiculopathy, and disc related pain conditions. Though evidence is sparse, PRP may be beneficial for use for treatment of disc related spine pain and radiculopathy. Results from PRP use for facet mediated pain is inconsistent while use with spinal fusion may inhibit osseous integration. PRP may have a role in treatment of spine related conditions particularly for disc related pain and radiculopathy though further studies are needed to validate existing findings.
The relationship between chronic pain and dementia risk has been extensively studied, but findings remain inconclusive. We conducted an updated meta-analysis to synthesize evidence from recent large-scale cohort studies. Two authors independently and systematically searched PubMed, Web of Science, Embase, Cochrane Library, and Chinese National Knowledge Infrastructure for cohort studies published through April 2025, with a minimum follow-up of one year. Hazard ratios (HRs) were considered equivalent to risk ratios (RRs) assuming low event rates. Random-effect models pooled risk ratios (RR) with 95
Ehlers–Danlos syndrome (EDS) is a congenital connective tissue disorder that is often marked by chronic pain and considerable functional impairment. Pain in EDS is typically multifaceted, involving musculoskeletal, neuropathic, autonomic, and centralized pain components. The present investigation, therefore, aims to examine common pain phenotypes and mechanisms in EDS and to discuss strategies for interdisciplinary pain management briefly. Recent studies have identified multiple sources of pain etiologies in EDS, including joint instability, repetitive microtrauma, small fiber neuropathy, and dysfunctional central pain processing. There is also growing evidence that nociceptive pain mechanisms and psychological factors may play a role in pain experience. Furthermore, current literature promotes multidisciplinary care models that synthesize physical therapy targeting joint stabilization and neuromuscular control, symptom-specific pharmacologic therapy, and psychological interventions. In addition, recent studies have investigated complementary therapies, including trigger-point injections, that may provide benefit. Despite this, high-quality evidence supporting interventional and specific pharmacologic regimens remains sparse. EDS pain remains multifaceted and requires an individualized and mechanism-informed approach to treatment. Integrated care models that include rehabilitation, phenotype-guided pharmacotherapy, and behavioral interventions form the bedrock of management. Ongoing research is necessary to refine phenotype-driven treatment strategies further.
