An Update on Emerging Regenerative Medicine Applications: The Use of Extracellular Vesicles and Exosomes for the Management of Chronic Pain.

PURPOSE OF REVIEW: Chronic pain affects nearly two billion people worldwide, surpassing heart disease, diabetes, and cancer in terms of economic costs. Lower back pain alone is the leading cause of years lived with disability worldwide. Despite limited treatment options, regenerative medicine, particularly extracellular vesicles (EVs) and exosomes, holds early promise for patients who have exhausted other treatment options. EVs, including exosomes, are nano-sized structures released by cells, facilitating cellular communication through bioactive molecule transfer, and offering potential regenerative properties to damaged tissues. Here, we review the potential of EVs and exosomes for the management of chronic pain. RECENT FINDINGS: In osteoarthritis, various exosomes, such as those derived from synovial mesenchymal stem cells, human placental cells, dental pulp stem cells, and bone marrow-derived mesenchymal stem cells (MSCs), demonstrate the ability to reduce inflammation, promote tissue repair, and alleviate pain in animal models. In intervertebral disc disease, Wharton's jelly MSC-derived EVs enhance cell viability and reduce inflammation. In addition, various forms of exosomes have been shown to reduce signs of inflammation in neurons and alleviate pain in neuropathic conditions in animal models. Although clinical applications of EVs and exosomes are still in the early clinical stages, they offer immense potential in the future management of chronic pain conditions. Clinical trials are ongoing to explore their therapeutic potential further, and with more research the potential applicability of EVs and exosomes will be fully understood.

Case Report: Glossopharyngeal Allodynia-Related Odynophagia and Dysphagia Post Anterior Cervical Discectomy and Fusion Managed with Glossopharyngeal Nerve Block.

Dysphagia after anterior cervical spine surgery has a 5% to 15% incidence beyond 1-year postsurgery, often attributed to mechanical factors such as pharyngeal thickening and epiglottis inversion. Despite normal neurological examination and electromyography, nerve distortion related to stretching also remains a possibility in these patients and may cause allodynia resulting in odynophagia and dysphagia. Current treatment options for dysphagia after anterior cervical discectomy and fusion are limited to local intraoperative steroid injections and tracheal traction exercises. In our patient, a glossopharyngeal nerve block was effectively used to manage the glossopharyngeal allodynia, thereby reducing the odynophagia and dysphagia, ultimately enhancing oral tolerance.

Virtual Reality in Acute and Chronic Pain Medicine: An Updated Review.

PURPOSE OF REVIEW: This review critically analyzes the recent literature on virtual reality's (VR) use in acute and chronic pain management, offering insights into its efficacy, applications, and limitations. RECENT FINDINGS: Recent studies, including meta-analyses and randomized controlled trials, have demonstrated VR's effectiveness in reducing pain intensity in various acute pain scenarios, such as procedural/acute pain and in chronic pain conditions. The role of factors such as immersion and presence in enhancing VR's efficacy has been emphasized. Further benefits have been identified in the use of VR for assessment as well as symptom gathering through conversational avatars. However, studies are limited, and strong conclusions will require further investigation. VR is emerging as a promising non-pharmacological intervention in pain management for acute and chronic pain. However, its long-term efficacy, particularly in chronic pain management, remains an area requiring further research. Key findings highlight that VR programs vary in efficacy depending on the specificity of the origin of pain.

Telehealth and Virtual Reality Technologies in Chronic Pain Management: A Narrative Review.

PURPOSE OF REVIEW: This review provides medical practitioners with an overview of the present and emergent roles of telehealth and associated virtual reality (VR) applications in chronic pain (CP) management, particularly in the post-COVID-19 healthcare landscape. RECENT FINDINGS: Accumulated evidence points to the efficacy of now well-established telehealth modalities, such as videoconferencing, short messaging service (SMS), and mobile health (mHealth) applications in complementing remote CP care. More recently, and although still in early phases of clinical implementation, a wide range of VR-based interventions have demonstrated potential for improving the asynchronous remote management of CP. Additionally, VR-associated technologies at the leading edge of science and engineering, such as VR-assisted biofeedback, haptic technology, high-definition three-dimensional (HD3D) conferencing, VR-enabled interactions in a Metaverse, and the use of wearable monitoring devices, herald a new era for remote, synchronous patient-physician interactions. These advancements hold the potential to facilitate remote physical examinations, personalized remote care, and innovative interventions such as ultra-realistic biofeedback. Despite the promise of VR-associated technologies, several limitations remain, including the paucity of robust long-term effectiveness data, heterogeneity of reported pain-related outcomes, challenges with scalability and insurance coverage, and demographic-specific barriers to patient acceptability. Future research efforts should be directed toward mitigating these limitations to facilitate the integration of telehealth-associated VR into the conventional management of CP. Despite ongoing barriers to widespread adoption, recent evidence suggests that VR-based interventions hold an increasing potential to complement and enhance the remote delivery of CP care.

Dorsal root ganglion stimulator-A targeted therapy for post-herpetic neuralgia: The Middle East Experience.

BACKGROUND: Post herpetic neuralgia (PHN) is a chronic neuropathic pain syndrome which presents after an episode of herpes zoster caused by the reactivation of varicella zoster virus. Conservative treatment starts with pharmacological measures using Anti-epileptics and Antidepressants. Some patients also respond well to epidural steroid injections too, but the effect is usually short lasting. Dorsal Root Ganglion Stimulator (DRG-S) has recently been suggested as a new treatment modality for PHN due to its selective targeting of the pathophysiologic focus. CASE SERIES: We are reporting three cases, who were suffering from neuropathic pain after an episode of herpes zoster. Pain and pain related suffering scores were high, even with multiple antiepileptics and opioid medications. They underwent DRG-S implant and appreciated more than 50% reduction of their pain score, meaningful reduction in the dose of medications along with significant improvement of their general well being measured using Generalized Anxiety Disorder Questionnaire (GAD-7), pain disability index (PDI), and 9 Question Patient Health Questionnaire (PHQ-9). To our knowledge this is the first report on DRG stimulator from the Middle East Region. CONCLUSION: DRG-S has potential to be a preferable treatment option in patients with refractory PHN and acts as a specific targeted therapy in the treatment of these patients.

Educational Curriculum for Peripheral Nerve Stimulation Developed by the North American Neuromodulation Society.

BACKGROUND: Peripheral nerve stimulation (PNS) is an effective neuromodulation therapy for chronic neuropathic and nociceptive pain. Although the total number of PNS implantations has increased over the last decade, no curriculum exists to guide training and learning of this therapy. The goal of the North American Neuromodulation Society (NANS) education committee is to develop a series of competency-based curriculums for neuromodulation therapies. The PNS curriculum is the latest part of such series, following the curriculums for spinal cord stimulation and intrathecal drug delivery system. MATERIALS AND METHODS: A multidisciplinary task force (anesthesiology, physical medicine and rehabilitation, neurosurgery, preventive medicine and public health, and neurology) was created by the educational committee of NANS to develop a PNS curriculum in accordance with the Accreditation Council for Graduate Medical Education (ACGME) milestones. The curriculum was created based on the best available evidence and expert knowledge (from our task force members) of available PNS systems. The final PNS curriculum was approved by the NANS board. RESULTS: A PNS curriculum was developed by the task force. Milestones included professionalism, practice-based learning, interpersonal communication, medical knowledge, systems-based practice, procedural skills, and patient care. Each milestone was defined into three categories: early learner, advanced learner, and practitioner. CONCLUSIONS: This manuscript provides a PNS training curriculum developed by a multidisciplinary task force of the NANS educational committee in accordance with the milestones described by ACGME for basic learners, advanced learners, and practitioners. This curriculum will help provide a structured training and evaluation process for obtaining proficiency in PNS treatment(s).

North American Neuromodulation Society Educational Curriculum for Intrathecal Drug Delivery Systems Implantation and Management.

OBJECTIVES: Intrathecal drug delivery systems (IDDSs) are used for the treatment of pain and spasticity. A wide range of educational criteria exist for these devices. The North American Neuromodulation Society (NANS) Education Committee developed a comprehensive IDDS curriculum to function as a standard for physician graduate education and assessment through training and into practice. MATERIAL AND METHODS: A multidisciplinary and diverse task force gathered by the NANS Education Committee met in person and virtually over several sessions and developed an IDDS curriculum modeling their previous work on spinal cord stimulation and following the Accreditation Council for Graduate Medical Education (ACGME) Milestones. There were iterative revisions and adaptations to the curriculum, and the final version was approved by the NANS Board of Directors. RESULTS: The curriculum was developed with distinction between implanting physicians and managing physician and physicians who perform both tasks. There is a lateral temporal progression from early learner to practitioner, with advanced learner in the middle. In addition, there is a modular vertical organization that divides the curriculum into the six educational competencies outlined by the ACGME. CONCLUSION: A comprehensive, modular, graduated, and segmented educational curriculum for IDDSs was developed by NANS. We propose the curriculum to be the standard for guidance and assessment of trainees and physicians pursuing training in implanting or managing IDDSs.

The American Society of Pain and Neuroscience (ASPN) Evidence-Based Clinical Guideline of Interventional Treatments for Low Back Pain.

Introduction: Painful lumbar spinal disorders represent a leading cause of disability in the US and worldwide. Interventional treatments for lumbar disorders are an effective treatment for the pain and disability from low back pain. Although many established and emerging interventional procedures are currently available, there exists a need for a defined guideline for their appropriateness, effectiveness, and safety. Objective: The ASPN Back Guideline was developed to provide clinicians the most comprehensive review of interventional treatments for lower back disorders. Clinicians should utilize the ASPN Back Guideline to evaluate the quality of the literature, safety, and efficacy of interventional treatments for lower back disorders. Methods: The American Society of Pain and Neuroscience (ASPN) identified an educational need for a comprehensive clinical guideline to provide evidence-based recommendations. Experts from the fields of Anesthesiology, Physiatry, Neurology, Neurosurgery, Radiology, and Pain Psychology developed the ASPN Back Guideline. The world literature in English was searched using Medline, EMBASE, Cochrane CENTRAL, BioMed Central, Web of Science, Google Scholar, PubMed, Current Contents Connect, Scopus, and meeting abstracts to identify and compile the evidence (per section) for back-related pain. Search words were selected based upon the section represented. Identified peer-reviewed literature was critiqued using United States Preventive Services Task Force (USPSTF) criteria and consensus points are presented. Results: After a comprehensive review and analysis of the available evidence, the ASPN Back Guideline group was able to rate the literature and provide therapy grades to each of the most commonly available interventional treatments for low back pain. Conclusion: The ASPN Back Guideline represents the first comprehensive analysis and grading of the existing and emerging interventional treatments available for low back pain. This will be a living document which will be periodically updated to the current standard of care based on the available evidence within peer-reviewed literature.

Best Practices for Minimally Invasive Lumbar Spinal Stenosis Treatment 2.0 (MIST): Consensus Guidance from the American Society of Pain and Neuroscience (ASPN).

Introduction: Lumbar spinal stenosis (LSS) is a common spinal disease of aging with a growing patient population, paralleling population growth. Minimally invasive treatments are evolving, and the use of these techniques needs guidance to provide the optimal patient safety and efficacy outcomes. Methods: The American Society of Pain and Neuroscience (ASPN) identified an educational need for guidance on the prudent use of the innovative minimally invasive surgical therapies for the treatment of symptomatic LSS. The executive board nominated experts spanning anesthesiology, physiatry, orthopedic surgery, and neurosurgery based on expertise, publications, research, diversity and field of practice. Evidence was reviewed, graded using the United States Preventive Services Task Force (USPSTF) criteria for evidence and recommendation strength and grade, and expert opinion was added to make consensus points for best practice. Results: The world literature in English was searched using Medline, EMBASE, Cochrane CENTRAL, BioMed Central, Web of Science, Google Scholar, PubMed, Current Contents Connect, Scopus, and meeting abstracts to identify and compile the evidence (per section) for LSS-related pain. Search words were selected based upon the section represented. Identified peer-reviewed literature was critiqued using USPSTF criteria and consensus points are presented. Discussion: The algorithm for patient selection in the management of symptomatic spinal stenosis is evolving. Careful consideration of patient selection and anatomic architecture variance is critical for improved outcomes and patient safety. Conclusion: ASPN created a guidance for best practice for minimally invasive surgical treatment of symptomatic spinal stenosis.

Dorsal root ganglion stimulation for the treatment of severe intractable pain related to obturator nerve entrapment neuropathy: A case report.

A 61-year-old Caucasian female, with severe obturator neuropathy following a left pubic ramus fracture was treated successfully with dorsal root ganglion stimulation (DRGS). Both conservative management and a dual-lead dorsal column spinal cord stimulator did not provide effective long-term results. The dorsal root ganglion (DRG) trial was completed five years following the initial fracture, resulting in 90 % pain relief. A permanent device was implanted and after one year, 90 % pain relief was still sustained. DRGS has applicability in future treatment algorithms for patients with mixed nociceptive and neuropathic groin pain refractory to conservative management.

Sphenopalatine Ganglion Block and Radiofrequency Ablation: Technical Notes and Efficacy.

Background: Sphenopalatine ganglion (SPG) blockade or lesioning can offer significant pain relief for cluster headaches (CHs) and a variety of other pain syndromes involving the head and face. Methods: We reviewed the literature on the efficacy of SPG block and radiofrequency ablation (RFA) using PubMed and Google Scholar. Results: The infrazygomatic technique can be used to directly access the SPG for injection of local anesthetic or lesioning using RFA. Important technical points to achieve these procedures are described. SPG blockade efficacy is supported by randomized controlled studies but SPG RFA is not. Conclusion: Targeting the SPG is a promising treatment option for refractory CHs. RFA and neuromodulation have the potential to offer long-term significant pain relief, but more randomized studies are needed to demonstrate their efficacy.

Atypical Facial Pain: a Comprehensive, Evidence-Based Review.

PURPOSE OF REVIEW: The purpose of this article is to focus on an excruciating disorder of the face, named atypical facial pain or persistent idiopathic facial pain (PIFP). It is considered an underdiagnosed condition with limited treatment options. Facial pain can be a debilitating disorder that affects patients' quality of life. Up to 26% of the general population has suffered from facial pain at some point in their lives. It is important to highlight the different types of facial pain to be able to properly manage this condition accordingly. RECENT FINDINGS: Newer interventional modalities such as pulsed radiofrequency ablation (PFR) of the sphenopalatine ganglion, peripheral nerve field stimulators (PNFS), and botulinum toxin injections have promising results. In summary, more prospective studies such as randomized controlled trials are necessary to explore the possibility of their more widespread use as viable procedures for the treatment of PIFP. In this review article, we describe the workup and diagnosis of PIFP and highlight recent literature regarding the pathophysiology and treatment of PIFP. PIFP is an excruciating disorder of the face often misdiagnosed as trigeminal neuralgia (TN) However, unlike TN symptoms, the pain is persistent rather than intermittent, usually unilateral, and without autonomic signs or symptoms. When a clinician encounters a patient with neuropathic facial pain whose symptoms are incongruent with the more common etiologies, the diagnosis of atypical facial pain must be entertained. Treatment of PIFP is multidisciplinary. Unfortunately, few randomized controlled trials for the treatment of PIFP exist. However, there are a select number of pharmacological, non-pharmacological, and interventional treatment options that have proven to be moderately effective.

A Rare Case of Transverse Sinus Venous Thrombosis Simulating Postdural Puncture Headache After Cervical Epidural Injection.

Postdural puncture headache (PDPH) is a feared complication related to epidural steroid injections. We report a unique case in which all subjective and objective findings indicated the diagnosis of PDPH. However, the patient failed appropriate conservative and interventional management. Therapeutic failure prompted further investigation to establish the correct diagnosis of cerebral venous sinus thrombosis. Cerebral venous sinus thrombosis is a rare, difficult to diagnose, but potentially lethal disorder with nonspecific and variable clinical presentations, including headache and focal neurological deficits. Performing magnetic resonance imaging and magnetic resonance venogram should be considered early, especially in patients who fail to respond to standard interventions for PDPH.

Coccydynia: an overview of the anatomy, etiology, and treatment of coccyx pain.

BACKGROUND: Despite its small size, the coccyx has several important functions. Along with being the insertion site for multiple muscles, ligaments, and tendons, it also serves as one leg of the tripod-along with the ischial tuberosities-that provides weight-bearing support to a person in the seated position. The incidence of coccydynia (pain in the region of the coccyx) has not been reported, but factors associated with increased risk of developing coccydynia include obesity and female gender. METHODS: This article provides an overview of the anatomy, physiology, and treatment of coccydynia. RESULTS: Conservative treatment is successful in 90% of cases, and many cases resolve without medical treatment. Treatments for refractory cases include pelvic floor rehabilitation, manual manipulation and massage, transcutaneous electrical nerve stimulation, psychotherapy, steroid injections, nerve block, spinal cord stimulation, and surgical procedures. CONCLUSION: A multidisciplinary approach employing physical therapy, ergonomic adaptations, medications, injections, and, possibly, psychotherapy leads to the greatest chance of success in patients with refractory coccyx pain. Although new surgical techniques are emerging, more research is needed before their efficacy can be established.

How to assess a new patient for a multidisciplinary chronic pain rehabilitation program: a review article.

BACKGROUND: Chronic pain is a debilitating condition that affects people all over the world. To effectively treat chronic pain patients, assignment to patient-centered functional restoration and psychological pain rehabilitation programs at an early stage is essential. METHODS: This article describes the initial patient screening and evaluation process for an interdisciplinary chronic pain rehabilitation program and highlights the relevant points that should be covered in each section of the initial assessment. RESULTS: A thorough, detailed history that includes an evaluation of the patient's pain, functional limitations, prior medications, prior procedures/interventions, substance abuse, and psychiatric disorders, as well as the patient's social, legal, and developmental histories, are key to the proper screening and appropriate treatment of patients with chronic pain. CONCLUSION: Thorough initial evaluation of patients is essential for proper enrollment in a chronic pain rehabilitation program. Such programs allow early treatment and reduce unnecessary health costs. Future prospective studies are needed to identify additional screening methods and triage tools to allow early admission of appropriate patients to these rehabilitation programs.

Successful treatment of occipital neuralgia with implantable peripheral nerve stimulation in a pacemaker-dependent patient.

BACKGROUND: Peripheral nerve stimulation has been used to treat patients with occipital nerve-related chronic headaches who have been unsuccessful with less invasive therapeutic approaches. Patients with pacemaker-dependent cardiac conduction abnormalities require unique consideration prior to the implantation of peripheral nerve stimulators because the placement of the devices may lead to failure of the systems secondary to electromagnetic interference or crosstalk between the devices. CASE REPORT: An 86-year-old female who suffered from chronic right-sided cervicogenic headaches and neck pain had received only temporary relief from previous treatments. Additional comorbidities included longstanding pacemaker-dependent atrioventricular node conduction disease. Because the extent to which nerve stimulators electrically interact with pacemakers is unclear, we tunneled the leads to the lumbar region of the back and placed the generator on the contralateral side to the pacemaker to minimize the chance that the 2 devices would interfere. The patient has remained pain free for 1 year since implantation. CONCLUSION: Although no current published trials evaluate the degree of interference between medical devices, case reports increasingly suggest that simultaneous implantation of a spinal cord stimulator and pacemaker is safe as long as precautions are taken and the devices are checked periodically, particularly when the devices are adjusted.

Kyphoplasty increases vertebral height, decreases both pain score and opiate requirements while improving functional status.

Vertebral compression fractures can result from advanced osteoporosis, or less commonly from metastatic or traumatic insults to the vertebral column, and result in disabling pain and decreased functional capacity. Various vertebral augmentation options including kyphoplasty aim at preventing the sequelae of pain and immobility that can develop as the result of the vertebral fractures. The mechanism for pain relief following kyphoplasty is not entirely understood, and the restoration of a portion of the lost vertebral height is a subject of debate. We retrospectively reviewed radiographic imaging, pain relief, analgesic intake and functional outcomes in 67 consecutive patients who underwent single- or multilevel kyphoplasty with the primary goal of quantifying the restoration of lost vertebral height. We observed a mean of 45% of the lost vertebral height restored postprocedurally. Secondarily, kyphoplasty was associated with significant decreases in pain scores, daily morphine consumption and improvement in patient-reported functional measures.

Differential epidural block predicts the success of visceral block in patients with chronic visceral abdominal pain.

BACKGROUND AND AIMS: Differential thoracic epidural regional block, also known as a differential neural block (DNB), involves the placement of an epidural catheter placed in the thoracic epidural space to achieve appropriate anesthesia in a dermatomal distribution. This is a retrospective case series evaluating how well a DNB may predict success of subsequent visceral blockade in patients with chronic abdominal pain of visceral origin. METHODS: Of 402 patients who had a DNB performed for unexplained abdominal pain from January 2000 to January 2009, 81 patients were found to have results consistent with visceral pain and thus underwent subsequent visceral blockade. Basic demographic data, years of chronic pain, history of psychosocial issues, initial visual analog scale (VAS) pain score, pain location, and medication usage were documented in our electronic medical record database. Parameters regarding DNB and visceral blocks also were documented. Descriptive statistics were computed for all variables. The positive predictive value (PPV) for DNB for whom visceral block was successful (at least a 50% reduction in VAS) was calculated. Additionally, subjects with successful visceral blocks were compared to those with unsuccessful visceral blocks. PARTICIPANTS: All patients with chronic abdominal pain with normal gastrointestinal studies who underwent DNB. SETTING: Tertiary Outpatient Pain Management Clinic. DESIGN: Retrospective Cohort Study. RESULTS: Mean age of patients was 46 (± 15) years, 73% were female, and median duration of pain was 5 years. 67% of subjects were taking opioid analgesics. PPV of DNB was 70.4%. Only factor found to be statistically significant with visceral block success was baseline VAS with higher scores associated with DNB predictive success (6.8 ± 1.7 vs. 5.5, 1.8; P = 0.004). Use of membrane stabilizing medications was significantly more common in subjects for whom visceral block was not successful (46% vs. 25%; P = 0.058). Area underneath curve (AUC) for VAS was found to be 0.70 (95% CI: 0.57, 0.82), which signifies fair discrimination. CONCLUSION: Differential neural block is fairly predictive of subsequent visceral block success in patients with chronic abdominal pain of visceral origin. An initial VAS ≥ 5 provides a sensitivity of 93%, which implies that VAS < 5 may predict unsuccessful visceral block. Contrarily, a value of ≥ 8 would provide a specificity of 92% and may be used to predict success of subsequent visceral block.