Chronic Neuropathic Pain Syndromes Research Articles

Chronic Neuropathic Pain and Comorbid Depression Syndrome: From Neural Circuit Mechanisms to Treatment.

Chronic neuropathic pain and comorbid depression syndrome (CDS) is a major worldwide health problem that affects the quality of life of patients and imposes a tremendous socioeconomic burden. More than half of patients with chronic neuropathic pain also suffer from moderate or severe depression. Due to the complex pathogenesis of CDS, there are no effective therapeutic drugs available. The lack of research on the neural circuit mechanisms of CDS limits the development of treatments. The purpose of this article is to provide an overview of the various circuits involved in CDS. Notably, activating some neural circuits can alleviate pain and/or depression, while activating other circuits can exacerbate these conditions. Moreover, we discuss current and emerging pharmacotherapies for CDS, such as ketamine. Understanding the circuit mechanisms of CDS may provide clues for the development of novel drug treatments for improved CDS management.

Peripheral and central neurobiological effects of botulinum toxin A (BoNT/A) in neuropathic pain: a systematic review.

Botulinum toxin (BoNT), a presynaptic inhibitor of acetylcholine (Ach) release at the neuromuscular junction (NMJ), is a successful and safe drug for the treatment of several neurological disorders. However, a wide and recent literature review has demonstrated that BoNT exerts its effects not only at the "periphery" but also within the central nervous system (CNS). Studies from animal models, in fact, have shown a retrograde transport to the CNS, thus modulating synaptic function. The increasing number of articles reporting efficacy of BoNT on chronic neuropathic pain (CNP), a complex disease of the CNS, demonstrates that the central mechanisms of BoNT are far from being completely elucidated. In this new light, BoNT might interfere with the activity of spinal, brain stem, and cortical circuitry, modulating excitability and the functional organization of CNS in healthy conditions. Botulinum toxins efficacy on CNP is the result of a wide and complex action on many and diverse mechanisms at the basis of the maladaptive plasticity, the core of the pathogenesis of CNP. This systematic review aims to discuss in detail the BoNT's mechanisms and effects on peripheral and central neuroplasticity, at the basis for the clinical efficacy in CNP syndromes.

Pudendal neuralgia

Pudendal neuralgia is the most common type of neurogenic chronic pelvic pain and is defined as a chronic neuropathic pain syndrome caused by compression and/or neuropathy of the genital nerve and localized in the area of its sensory innervation. Pudendal neuralgia negatively affects daily activity and reduces the quality of life. The diagnosis of pudendal neuralgia is established on the basis of clinical manifestations and examination data in accordance with the Nantes criteria, while instrumental methods (ultrasound, magnetic resonance and computed tomography, electrodiagnostic methods) do not allow verifying the diagnosis due to significant limitations. Currently, there are no unambiguous recommendations and standards for the treatment of pudendal neuralgia, however, a combination of different methods and a personalized approach allows in some cases to achieve significant success and long-term pain control. The article highlights in detail the anatomical features of the pudendal nerve, examines the possibilities and stages of diagnosis of pudendal neuralgia, and provides an overview of therapeutic methods from the standpoint of evidence-based medicine.

The association of self-reported symptoms of central sensitization and sleep disturbances in neuropathic pain.

Patients with neuropathic pain (NP) report a higher impairment of quality of life and sleep than patients with chronic pain without neuropathic characteristics. These include somatosensory peculiarities like allodynia, a surrogate marker for central sensitization. This study aimed to investigate the relation between symptoms of central sensitization and sleep disturbances in patients with NP. Within this cross-sectional study, data sets of 3339 patients with chronic NP syndromes (painful diabetic polyneuropathy, n = 543; postherpetic neuralgia, n = 1480) or complex regional pain syndromes (CRPS, n = 1316) were analyzed. Neuropathic pain symptoms were assessed with the painDETECT questionnaire (PD-Q), depression with the Patient Health Questionnaire-9, and sleep impairment with items of the Medical Outcomes Study Sleep Scale in 4 subscales. The association of demographic/clinical data, somatosensory phenotype, depression, and pain intensity with sleep impairment was assessed by unadjusted Spearman correlation analyses and multivariable regression analyses. Sleep impairment was observed in all pain aetiologies although with some significant differences in the single sleep items. The intensity of the individual PD-Q items differed to some extent between the 3 pain entities, whereas the PD-Q sum score was similar. Thermal hyperalgesia and burning assessed by the PD-Q were significantly associated with sleep disturbance, adequacy, and quantity but not with sleep somnolence. Only depression and self-reported allodynia had a significant relation to all 4 sleep elements. Beside depression, allodynia as a surrogate marker hints to a possible impact of central sensitization on the sleep disruption of patients with NP.

Acceptability, usability and feasibility of experienced sampling method in chronic secondary pain syndromes.

In chronic pain syndromes, symptoms can fluctuate and change over time. Standard questionnaires cannot register these fluctuations. Nonetheless, the experience sampling method (ESM) is developed to collect momentary measurements of everyday complaints, tracing fluctuations in symptoms and disabling factors over time. Although valuable information can be collected in this way, assessment may also be a burden. This study aimed to investigate the acceptability, usability, and feasibility of ESM in chronic secondary pain syndromes, in a single-center study in the Netherlands. A prospective observational study with repeated measurements was conducted in patients with chronic secondary neuropathic and musculoskeletal pain syndromes, including small fiber neuropathy, spinal cord injury, and rheumatoid disorder. Thirty-four participants were included and filled in the ESM, of whom 19 were diagnosed with small fiber neuropathy, 11 with spinal cord injury, and 4 with a rheumatoid disorder. The mean age was 54.7 ± 13.9 years (range: 23-77) of whom 52.9% were female. In total, 19 participants filled in the general and user-friendliness evaluation about the acceptability and usability of the ESM. The general evaluation showed no influence of ESM on participants' social contacts (mean 1.47, SD 1.12), activities (mean 1.74, SD 1.44), and mood (mean 1.89, SD 1.59). The answers options of ESM were a good representation of the experiences of participants (mean 4.58, SD 1.77). Regarding feasibility, the overall response rate for answering the beep signals of ESM was 44.5% in total. The missing rate per person varied from 13% to 97% with a median of 54.1%. The general evaluation and the user-friendliness revealed sufficient outcomes in favor of the ESM application. ESM seems a promising measurement tool to use in secondary chronic pain syndromes.

Role of Sensory Pathway Injury in Central Post-Stroke Pain: A Narrative Review of Its Pathogenetic Mechanism.

Central post-stroke pain (CPSP) is a severe chronic neuropathic pain syndrome that is a direct result of cerebrovascular lesions affecting the central somatosensory system. The pathogenesis of this condition remains unclear owing to its extensive clinical manifestations. Nevertheless, clinical and animal experiments have allowed a comprehensive understanding of the mechanisms underlying CPSP occurrence, based on which different theoretical hypotheses have been proposed. We reviewed and collected the literature and on the mechanisms of CPSP by searching the English literature in PubMed and EMBASE databases for the period 2002-2022. Recent studies have reported that CPSP occurrence is mainly due to post-stroke nerve injury and microglial activation, with an inflammatory response leading to central sensitization and de-inhibition. In addition to the primary injury at the stroke site, peripheral nerves, spinal cord, and brain regions outside the stroke site are involved in the occurrence and development of CPSP. In the present study, we reviewed the mechanism of action of CPSP from both clinical studies and basic research based on its sensory pathway. Through this review, we hope to increase the understanding of the mechanism of CPSP.

Neuropathic pain in dry eye syndrome. Part 2. Clinical picture, diagnosis and treatment

Burning eye syndrome is a chronic neuropathic pain syndrome, which is characterized by dysesthesia, spontaneous pain, allodynia and hyperalgesia. The review describes clinical features and presents available data on possible methods of diagnosis and therapy of this condition.

СИНДРОМ СРЕДИННОЙ ДУГООБРАЗНОЙ СВЯЗКИ (СИНДРОМ ДАНБАРА) КАК МУЛЬТИДИСЦИПЛИНАРНАЯ ПРОБЛЕМА. КЛИНИЧЕСКОЕ НАБЛЮДЕНИЕ И ЛИТЕРАТУРНАЯ СПРАВКА

Introduction. Median arcuate ligament syndrome (MALS, Dunbar syndrome) is a rare vascular compression syndrome caused by extravascular compression of the celiac trunk (CT) and celiac plexus by the median arcuate ligament of the diaphragm and is one of the causes of chronic abdominal ischemia and neuropathic pain syndrome. Clinical observation. A woman, 36 years old, was hospitalized with complaints of abdominal pain of moderate intensity, diarrhea up to 10 times a day, weight loss of 11 kg over the past year. Inflammatory bowel disease, gluten enteropathy, lymphoma of the small intestine, malabsorption syndrome, pathology of the endocrine system was excluded. Abdominal high-resolution computed tomography (HRCT) angiography was performed. Signs of extravascular compression of CT up to 90% with a thickened median arcuate ligament with the formation of a U-shaped deformation were revealed. Laparoscopic decompression surgery was performed with simultaneous transluminal angioplasty, which led to a decrease in compression and disappearance of clinical symptoms. After 18 months, clinical improvement persisted, diarrhea disappeared. HRCT angiography and ultrasound duplex examination (USDE) showed sufficient blood flow in the CT system. During the follow-up period, the patient had moderate neuropathic pain and anxiety and depressive disorders requiring appropriate correction. Conclusion. The diagnostic and therapeutic approach to MALS should be patient-centered and requires the involvement of a team of specialists. Laparoscopic decompression is an effective treatment and can provide immediate symptoms relief. The results of the intervention can be assessed by HRCT angiography and USDE (methods supplementing each other). Correction of neuropathic pain syndrome and anxiety-depressive disorder is of great importance for improving the patient's quality of life.

Эффективность антиноцицептивного обеспечения при множественных эндодонтических вмешательствах

In modern medicine, including dentistry, pain is one of the leading issues as pain syndrome is one of the most common in most human diseases. However, pain in the maxillofacial region has its own characteristics. The tissues of the oral cavity are very richly innervated compared to other organs, which affects the greater sensitivity of this area. Patients most often seek medical help for pain-related reasons, which requires mandatory anesthesia. The endodontic treatment for complicated forms of carious lesions is based on invasive intervention. In addition to stress, there are other types of adaptive reactions of the body. A natural consequence of this is the initiation of nociceptive, neurovegetative and psychoemotional reactions. The result is the formation of chronic postoperative neuropathic pain syndromes affecting the dental health and life quality of the patient. Up to 70 % of patients' complaints are acute pain when seeking emergency care – this statistic is cited by the International Association for the Study of Pain (IASP, 2011). Pain is the main reason for patients seeking dental care. It forms the painful behavior of a person, while having an adverse effect on daily activities, which reduces the life quality of the patient.

Changes in Immunological Parameters and Neurotrophic Factors in Patients with Compression, Post-traumatic Non-gunshot and Gunshot Neuropathies and Plexopathies

Introduction: Chronic pain, which usually occurs after traumatic damage to nerves and plexuses, is an additional burden on the patient's quality of life, which is already impaired due to motor, sensory and autonomic deficits. The aim is to study and clarify changes in immunological parameters and neurotrophic factors in patients with compression, post-traumatic non-gunshot and gunshot neuropathies and plexopathies. Materials and Methods: The study included 93 men aged 21 to 59 with neuropathy and plexopathy of traumatic and non-traumatic origin, divided into 3 groups. Patients underwent clinical and neurological examination starting at the onset of clinical manifestations and in the dynamics, electromyography, and ultrasound. The immunological examination was performed from 12 to 24 months, starting at the onset of the disease. Results: Differences between the study groups in the concentration of circulating immune complexes and lymphocytotoxicity and decrease in CD4 + T lymphocytes were statistically significant. In the NBT-test results, which characterize the difference between spontaneous and zymosan-stimulated oxygen-dependent phagocytosis, it was found that the cells oxidized granules of nitroblue tetrazolium dye with different degrees of intensity, depending on the regenerative capacity of enzymes. We found an increase in the quantitative content of the beta-NGF 303 [35.2; 504.5] pg/ml in the blood of patients of group III with post-traumatic gunshot neuropathies and plexopathies accompanied by chronic neuropathic pain syndrome at a statistically significant level (Kruskal-Wallis test, p=0.0181). Conclusion: The study showed a statistically significant (p<0.05) violations of the regulatory link of immune system in patients with post-traumatic gunshot neuropathies and plexopathies, increased circulating immune complexes level, disorders of oxygen-dependent and oxygen-independent phagocytosis, reduced enzymatic regenerative capacity, significant increase in beta-NGF, Thus, as a result of the study, we found statistically significant (p<0.05) violations of the regulatory link of immune system in patients with post-traumatic gunshot neuropathies and plexopathies, increased circulating immune complexes level, disorders of oxygen-dependent and oxygen-independent phagocytosis, reduced enzymatic regenerative capacity, significant increase in beta-NGF 303 [35.2; 504.5] pg / ml, indicating the ongoing process of chronic inflammation, stimulation of the sympathetic nervous system and sensory fibers, which leads to the maintenance and severity of chronic neuropathic pain even after 12 months or more since the injury with damage to nerves and plexuses of the limbs.

Regression of chronic pain syndrome refractory to opioid pharmacotherapy in a patient after implantation of a spinal cord neurostimulator: case report

BACKGROUND: Pain in cancer patients, often poorly treated, cause severe distress for patients and their caregivers, and significantly reduces quality of life. Modern guides for the medical treatment of chronic pain in cancer patients are not effective in all cases, especially when chronic neuropathic pain syndrome occurs. In this regard, there is a need for a multidisciplinary personalized approach to the tactics of chronic pain management in favor of surgical methods at earlier stages of this condition. Nowadays neuromodulation is widely used for the treatment of neuropathic chronic pain syndrome in patients with various pathologies, whereas it is not used routinely in cancer patients.
 CLINICAL CASE DESCRIPTION: We introduce a case report of successfully applied neuromodulation in patient with severe chronic pain syndrome due to rectal cancer. Epidural spinal cord stimulation at Th10Th12 levels allowed to stop the systemic use of opioids and achieve long-term remission. Spinal cord stimulation has shown itself to be very promising and significantly improved patients quality of life.
 CONCLUSIONS: Our case report evidently shows that current chronic pain management guides and treatment recommendations needs a revision and neuromodulation usage in category of cancer patients should be considered.

Contemporary opioid-sparing approaches after hysterectomy

Hysterectomy is one of the most common interventions in the field of operative gynecology that can be done in various surgical ways. Regardless of the operative technique, the uterine ablation causes moderate to severe postoperative pain. The pain has both visceral and somatic origins. High-quality analgesia after hysterectomy is an important precondition for obtaining rapid convalescence and dehospitalization in the conditions of a psychoemotional comfort. Good analgesia decreases the risk of developing chronic neuropathic pain syndromes. Morphine mimetics are the most commonly used analgesics for obtaining a pain relief after hysterectomy. Their powerful analgesic effect, unfortunately, is related to a number of side effects such as nausea, vomiting, alteration of consciousness, and others. This evokes the research of new analgesic strategies in postoperative pain relief that are able to reduce the use of opioids for acute pain relief. The simultaneous use of different analgesic medicaments and techniques, with various modes of action and site of application, constitutes the modern approach in the aim of reducing opioid consumption. This article provides a brief overview of the modern possibilities for the implementation of multimodal analgesia in the postoperative period after hysterectomy. The main groups of different analgesics, their potential, side effects and recommended dosages are discussed. We have made a brief presentation of the regional anesthesia techniques and local anesthetic agents that have a potential to provide pain relief after hysterectomy.

PO030 / #1031 DORSAL ROOT GANGLION STIMULATION FOR TREATMENT OF REFRACTORY POSTHERPETIC NEURALGIA: PATIENT SERIES: E-POSTER VIEWING

Postherpetic neuralgia (PHN) is a chronic neuropathic pain syndrome - a common complication of reactivated varicella zoster infection (the disease commonly known as herpes zoster). PHN is considered a major clinical concern, mostly due to relative ineffectiveness of standard chronic pain management. Current treatment consensus recommends using a multi-modal treatment strategy for PHN, which includes variety of pain medications (TCA, anticonvulsants, SSRI, SNRI) and a number of invasive procedures (including anaesthetic blockades, botulotoxin injections and others), with invasive procedures mostly reserved for refractory cases.

Spinal cord stimulation for treatment of chronic neuropathic pain in adolescent patients: a single-institution series, systematic review, and individual participant data meta-analysis.

Neuropathic pain is undertreated in children. Neurosurgical treatments of pediatric chronic pain are limited by the absence of both US Food and Drug Administration approval and pediatric-specific hardware, as well as weak referral patterns due to a lack of physician education. This study presents a single-institution retrospective case series of spinal cord stimulation (SCS) in children ≤ 19 years of age and a systematic review of SCS in children. The authors' findings may further validate the role of SCS as an effective treatment modality for varied neuropathic pain syndromes found in pediatric patients. The study was a single-center, single-surgeon, retrospective case series of individuals treated between July 2017 and May 2022. The outcomes for pediatric patients with chronic neuropathic pain syndromes indicated by the multidisciplinary pain clinic for evaluation for SCS were cataloged. A systematic review and individual participant data (IPD) meta-analysis was performed for cases treated until May 2022, using PubMed, EMBASE, and Scopus to characterize outcomes of children with neuropathic pain treated with SCS. Twelve patients were evaluated and 9 were indicated for percutaneous or buried lead trials. Seven female and 2 male patients between the ages of 13 and 19 years were implanted with trial leads. Eight of 9 (89%) patients went on to receive permanent systems. The average trial length was 6 days, and the length of stay for both trial and implant was less than 1 day. Complication rates due to CSF leaks were 22% and 0% for trial and implant, respectively. Visual analog scale pain scores decreased from 9.2 to 2.9 (p = 0.0002) and the number of medications decreased from 4.9 to 2.1 (p = 0.0005). Functional status also improved for each patient. A systematic review identified 13 studies describing pediatric patients with SCS, including 12 providing IPD on 30 patients. In the IPD meta-analysis, pain was reduced in 16/16 (100%) of patients following surgery and in 25/26 (96.2%) at last follow-up. Medication use was decreased in 16/21 (76.2%), and functional outcomes were improved in 29/29 (100%). The complication rate was 5/30 (16.7%). SCS effectively decreases pain and medication use for pediatric neuropathic pain syndromes. Patients also report improved functional status, including improved matriculation, gainful employment, and physical activity. There is minimal high-quality literature describing neuromodulation for pain in children. Neuromodulation should be considered earlier as a viable alternative to escalating use of multiple drugs and as a potential mechanism to address tolerance, dependence, and addiction in pediatric patients.

Resting-State Functional Connectivity Analyses: Brain Functional Reorganization in a Rat Model of Postherpetic Neuralgia.

Postherpetic neuralgia (PHN) is a chronic neuropathic pain syndrome, similar to other chronic pains, the mechanisms of which are not fully understood. To further understand the neural mechanism of this chronic pain and its transition, we performed functional magnetic resonance imaging (fMRI) scans on PHN rat models. Twelve PHN rat models were established by intraperitoneal injection of resiniferatoxin, with an additional 12 rats serving as controls. Nociceptive behavioral tests were performed on these rats and fMRI scans were performed on days 7 and 14 after modeling. Functional connection (FC) analysis was used to investigate the brain FC alterations associated with chronic pain in PHN rats, with the anterior cingulate cortex (ACC) as a seed. Nociceptive behavioral tests showed that PHN rats presented symptoms similar to those of PHN patients. FC analysis showed that compared to the control group, the PHN group showed different FC patterns on days 7 and 14. As can be seen, the brain FC alterations in the rat model of PHN changed dynamically, shifting from brain regions processing sensory information to regions processing emotions and motives.

Long-term safety and efficacy of sublingual ketamine troches/lozenges in chronic non-malignant pain management.

Chronic non-malignant pain is a disabling condition that results in a reduction in function and quality of life when inadequately managed. Sublingual ketamine has been shown to be efficacious for use in chronic pain. Despite its use for decades in chronic non-malignant pain, there is no published long-term data on safety, side-effects or adverse drug reactions. The aim of this case-series is to provide the initial evidence for safety and efficacy in this patient group. We present a retrospective review of 29 (n = 29) patients from a metropolitan tertiary pain service who have been receiving sublingual ketamine troches/lozenges between the period of 2012 and 2019. Patients were identified from the outpatient pain clinic, who had been admitted for inpatient subcutaneous ketamine infusions as part of opiate detoxification or management of central sensitisation due to a chronic neuropathic pain syndrome. An initial review was performed to check the patient started taking the ketamine troches. Each of these medical records was reviewed manually to extract information to a datasheet. There was a wide range of dosages used from 25 to 600 mg in divided doses. The duration of treatment ranged 2-89 months. There was no association with either the dosage or duration of treatment and frequency of side-effects. There was an overall reduction in the use of opioids, gabapentinoids or benzodiazepines in 59% of patients with 39% having a complete cessation of an analgesic agent. Side-effects were reported in 24%, but only 7% discontinued the treatment due to the side-effect (drowsiness). There were no reports of renal impairment, cystitis or hepatotoxicity. This retrospective case-series has demonstrated that sublingual ketamine is a safe and effective analgesic agent to use in chronic non-malignant pain management. It is indicated in a variety of chronic pain conditions and has an excellent safety profile, with no association between the frequency in side-effects and duration of therapy or total daily dosages. The study has also shown that the 'safe' dose may be higher than the previous consensus.

Cannabinoids for Symptom Management in Patients with Kidney Failure: A Narrative Review.

People with kidney failure can experience a range of symptoms that lead to suffering and poor quality of life. Available therapies are limited, and evidence for new treatment options is sparse, often resulting in incomplete relief of symptoms. There is growing interest in the potential for cannabinoids, including cannabidiol and tetrahydrocannabinol, to treat symptoms across a wide range of chronic diseases. As legal prohibitions are withdrawn or minimized in many jurisdictions, patients are increasingly able to access these agents. Cannabinoid receptors, CB1 and CB2, are widely expressed in the body, including within the nervous and immune systems, and exogenous cannabinoids can have anxiolytic, antiemetic, analgesic, and anti-inflammatory effects. Considering their known physiologic actions and successful studies in other patient populations, cannabinoids may be viewed as potential therapies for a variety of common symptoms affecting those with kidney failure, including pruritus, nausea, insomnia, chronic neuropathic pain, anorexia, and restless legs syndrome. In this review, we summarize the pharmacology and pharmacokinetics of cannabinoids, along with what is known about the use of cannabinoids for symptom relief in those with kidney disease, and the evidence available concerning their role in management of common symptoms. Presently, although these agents show varying efficacy with a reasonable safety profile in other patient populations, evidence-based prescribing of cannabinoids for people with symptomatic kidney failure is not possible. Given the symptom burden experienced by individuals with kidney failure, there is an urgent need to understand the tolerability and safety of these agents in this population, which must ultimately be followed by robust, randomized controlled trials to determine if they are effective for symptom relief.

ID:16015 Long-Term Pain Relief From Erector Spinae Plane Block in Post-Mastectomy Pain Syndrome

Post-mastectomy pain syndrome (PMPS) is a common complication of surgical procedures for the treatment of breast cancer, particularly in procedures involving the axilla. It is a chronic neuropathic pain syndrome typically attributed to direct nerve injury, often lateral cutaneous branches of intercostal nerves T3-6. Erector spinae plane blocks (ESPB) appear to provide long-term analgesia, beyond the local anesthetic duration of action. This intervention is well-documented for the management of pain due to rib fractures, but it is also a relatively safe and quick treatment option for the treatment of PMPS.

Neuropathic Pain in Neurologic Disorders: A Narrative Review.

Neuropathic pain is defined as a painful condition caused by neurological lesions or diseases. Sometimes, neurological disorders may also be associated with neuropathic pain, which can be challenging to manage. For example, multiple sclerosis (MS) may cause chronic centralized painful symptoms due to nerve damage. Other chronic neuropathic pain syndromes may occur in the form of post-stroke pain, spinal cord injury pain, and other central pain syndromes. Chronic neuropathic pain is associated with dysfunction, disability, depression, disturbed sleep, and reduced quality of life. Early diagnosis may help improve outcomes, and pain control can be an important factor in restoring function. There are more than 100 different types of peripheral neuropathy and those involving sensory neurons can provoke painful symptoms. Accurate diagnosis of peripheral neuropathy is essential for pain control. Further examples are represented by gluten neuropathy, which is an extraintestinal manifestation of gluten sensitivity and presents as a form of peripheral neuropathy; in these unusual cases, neuropathy may be managed with diet. Neuropathic pain has been linked to CoronaVirus Disease (COVID) infection both during acute infection and as a post-viral syndrome known as long COVID. In this last case, neuropathic pain relates to the host’s response to the virus. However, neuropathic pain may occur after any critical illness and has been observed as part of a syndrome following intensive care unit hospitalization.

Neuromodulation in the Treatment of Painful Diabetic Neuropathy: A Review of Evidence for Spinal Cord Stimulation.

Neuropathies, the most common complication of diabetes, manifest in various forms, including entrapments, mononeuropathies or, most frequently, a distal symmetric polyneuropathy. Painful diabetic neuropathy (PDN) in the classic "stocking" distribution is a disease of increasing prevalence worldwide and a condition for which standard medical treatment only provides modest relief. Neuromodulation offers a potential alternative to pharmacotherapies given its demonstrated efficacy in other refractory chronic neuropathic pain syndromes. High-quality evidence from randomized controlled trials (RCTs) is available in these other settings for two approaches to spinal cord stimulation (SCS): (1) conventional low-frequency SCS (LF-SCS), which modulates axonal activity in the dorsal column and is paresthesia-dependent, and (2) high-frequency SCS delivered at 10 kilohertz (10 kHz SCS), which targets neurons in the superficial dorsal horn and is paresthesia-independent. This review examines the evidence for SCS from published RCTs as well as prospective studies exploring the safety and effectiveness of treating PDN with neuromodulation. Two RCTs enrolling 60 and 36 participants with PDN showed treatment with LF-SCS reduced daytime pain by 45% to 55% for up to two years. An RCT testing 10 kHz SCS versus conventional medical management (CMM) in 216 participants with PDN revealed 76% mean pain relief after six months of stimulation. None of the studies revealed unexpected safety issues in the use of neuromodulation in this patient population. These well-designed RCTs address the unmet need for improved PDN therapies and provide data on the safety, effectiveness, and durability of SCS therapy.