Gamma Knife Central Lateral Thalamotomy for Chronic Neuropathic Pain: A Single-Center, Retrospective Study.

BACKGROUND: Chronic neuropathic pain can be severely disabling and is difficult to treat. The medial thalamus is believed to be involved in the processing of the affective-motivational dimension of pain, and lesioning of the medial thalamus has been used as a potential treatment for neuropathic pain. Within the medial thalamus, the central lateral nucleus has been considered as a target for stereotactic lesioning. OBJECTIVE: To study the safety and efficacy of central lateral thalamotomy using Gamma Knife radiosurgery (GKRS) for the treatment of neuropathic pain. METHODS: We retrospectively reviewed all patients with neuropathic pain who underwent central lateral thalamotomy using GKRS. We report on patient outcomes, including changes in pain scores using the Numeric Pain Rating Scale and Barrow Neurological Institute pain intensity score, and adverse events. RESULTS: Twenty-one patients underwent central lateral thalamotomy using GKRS between 2014 and 2021. Meaningful pain reduction occurred in 12 patients (57%) after a median period of 3 months and persisted in 7 patients (33%) at the last follow-up (the median follow-up was 28 months). Rates of pain reduction at 1, 2, 3, and 5 years were 48%, 48%, 19%, and 19%, respectively. Meaningful pain reduction occurred more frequently in patients with trigeminal deafferentation pain compared with all other patients (P = .009). No patient had treatment-related adverse events. CONCLUSION: Central lateral thalamotomy using GKRS is remarkably safe. Pain reduction after this procedure occurs in a subset of patients and is more frequent in those with trigeminal deafferentation pain; however, pain recurs frequently over time.

Complex regional pain syndrome type II caused by iatrogenic lateral dorsal cutaneous nerve injury: A case report.

RATIONALE: Complex regional pain syndrome (CRPS) is a painful condition classified as type I or II depending on the absence or presence of nerve injury, respectively. Injury to the lateral dorsal cutaneous nerve (LDCN), a branch of the sural nerve, is a rare occurrence observed after a sprain or procedures conducted on the lateral side of the ankle. PATIENT CONCERNS: A 38-year-old female, who had undergone prolotherapy for a sprain in the lateral side of the left ankle 3 months ago, presented with persistent causalgia and dysesthesia around the injection site. DIAGNOSIS: An electrodiagnostic study was conducted, which confirmed that the patient had peripheral neuropathy of the left LDCN. Considering the digital infrared thermal imaging and three-phase bone scan findings and the clinical presentation, the condition was diagnosed as CRPS type II due to iatrogenic LDCN injury according to the Budapest diagnostic criteria for CRPS. INTERVENTIONS: The patient was treated with steroid pulse therapy, physical therapy, and transcutaneous electrical nerve stimulation, as well as nonsteroidal anti-inflammatory drugs, pregabalin, and tricyclic antidepressants. OUTCOMES: After 1 month of treatment, allodynia of the left foot persisted, but the pain reduced from 6 points to 3 points on the numeric rating scale. Partial recovery of amplitude and conduction velocity was confirmed in the follow-up electrodiagnostic study. LESSONS: LDCN injury should be considered in patients who complain of persistent lateral ankle and foot paresthesia or pain after sprain or procedures performed on the lateral side of the ankle. Early diagnosis and treatment can lead to a good prognosis when the LDCN injury has progressed to CRPS.

Therapy Habituation at 12 Months: Spinal Cord Stimulation Versus Dorsal Root Ganglion Stimulation for Complex Regional Pain Syndrome Type I and II.

The ACCURATE randomized, controlled trial compared outcomes of dorsal root ganglion (DRG) stimulation versus tonic spinal cord stimulation (SCS) in 152 subjects with chronic lower extremity pain due to complex regional pain syndrome (CRPS) type I or II. This ACCURATE substudy was designed to evaluate whether therapy habituation occurs with DRG stimulation as compared to SCS through 12-months. A modified intention-to-treat analysis was performed to assess percentage pain relief (PPR) and responder rates at follow-up visits (end-of-trial, 1, 3, 6, 9, 12-months postpermanent implant) for all subjects that completed trial stimulation (DRG:N = 73, SCS:N = 72). For both groups, mean PPR was significantly greater at end-of-trial (DRG = 82.2%, SCS =0 77.0%) than all other follow-ups. Following permanent DRG system implantation, none of the time points were significantly different from one another in PPR (range = 69.3-73.9%). For the SCS group, PPR at 9-months (58.3%) and 12-months (57.9%) was significantly less than at 1-month (66.9%). The responder rate also decreased for the SCS group from 1-month (68.1%) to 12-months (61.1%). After stratifying by diagnosis, it was found that only the CRPS-I population had diminishing pain relief with SCS. DRG stimulation resulted in more stable pain relief through 12-months, while tonic SCS demonstrated therapy habituation at 9- and 12-months. Trial Registration: The ACCURATE study was registered at ClinicalTrials.gov with Identifier NCT01923285. PERSPECTIVE: This article reports on an ACCURATE substudy, which found that long-term therapy habituation occurred at 12-months with SCS, but not DRG stimulation, in patients with CRPS. The underlying mechanisms of action for these results remain unclear, although several lines of inquiry are proposed.

Terapia de oxigenación hiperbárica en el tratamiento del dolor / Hyperbaric oxygenation therapy in pain treatment

El dolor crónico constituye un reto terapéutico especial. Se presenta una revisión narrativa sobre el papel del tratamiento de oxigenación hiperbárica (TOHB) en el tratamiento del dolor neuropático, y sus aplicaciones en dolor crónico, síndromes neurosensitivos disfuncionales y oncodolor. El conocimiento de las indicaciones de TOHB en algiología y su aplicación en la práctica médica puede contribuir a mejorar la calidad de vida del paciente. (AU)

Chronic pain represents a special therapeutic challenge. We present a narrative review on the role of Hyperbaric Oxygen Therapy (HBOT) in the treatment of neuropathic pain, and its applications in chronic pain, dysfunctional neurosensitive syndromes and oncological pain. The knowledge of the indications of HBOT in algiology and its application in medical practice can contribute to improve the quality of life of the patient. (AU)

Neuromodulation of the Dorsal Root Ganglion for Chronic Postsurgical Pain.

OBJECTIVE: The objective of this study is to review the available evidence for dorsal root ganglion (DRG) stimulation for the treatment of complex regional pain syndrome type II (CRPS II; peripheral causalgia) associated with chronic neuropathic postsurgical pain (NPP). DESIGN: Available literature was identified through a search of the US National Library of Medicine's Medline database, PubMed.gov. References from published articles also were reviewed for relevant citations. RESULTS: The data published to date support the use of DRG stimulation to treat chronic NPP of the groin, knee, and foot. NPP following procedures such as thoracotomy, hernia surgery, and knee replacement surgery were identified as some of the conditions for which DRG stimulation is likely to be effective. CONCLUSION: DRG stimulation is known to be an effective treatment for focal neuropathic pain. Currently, NPP of the foot, groin, and knee all appear to be the conditions with the most clinical experience, backed by a limited but growing body of evidence. However, prospective studies lag behind real-world clinical experience and are needed to confirm these findings.

Risk Factors Associated with Lead Migration Requiring Revision in Dorsal Root Ganglion Stimulation.

BACKGROUND: Neuromodulation is an evolving therapy for chronic pain. Aiming to meet the limitations of traditional spinal cord stimulation, dorsal root ganglion (DRG) stimulation targets pain in a dermatomal distribution at the site of pain transmission. Despite these advantages, lead migration is a significant complication that hinders the long-term efficacy of DRG stimulation. This study aims to identify risk factors for lead migration requiring revision in DRG stimulation. METHODS: We performed a retrospective review of all subjects who had DRG stimulators implanted at T10-S2 by a single physician over a 2-year period. Their history was reviewed for the following: age, sex, diagnosis, lead placement, reported symptom relief, complications, and postoperative activity. RESULTS: In total, 19 cases of DRG stimulator implantation were identified. All patients reported pain relief, with 84.2% (16/19) describing >50% relief. In total, 31.6% of patients (6/19) developed lead migration and 15.8% of total implanted leads (9/57) migrated. Of the migrated leads, 4% (4/9) occurred at S1 and 33.3% (3/9) occurred at L4. The underlying etiology of lead migration was clear and preventable in 66.7% of patients (4/6). All patients who developed lead migration were women. CONCLUSIONS: Premature activity, hardware manipulation, and female sex appear to be associated with an increased risk for lead migration. Leads on the S1 and L4 locations may be more likely to migrate. Large trials are necessary to gain a more conclusive understanding of these risk factors for lead migration.

Update on the effects of graded motor imagery and mirror therapy on complex regional pain syndrome type 1: A systematic review.

Graded motor imagery (GMI) and mirror therapy (MT) is thought to improve pain in patients with complex regional pain syndrome (CRPS) types 1 and 2. However, the evidence is limited and analysis are not independent between types of CRPS. The purpose of this review was to analyze the effects of GMI and MT on pain in independent groups of patients with CRPS types 1 and 2. Searches for literature published between 1990 and 2016 were conducted in databases. Randomized controlled trials that compared GMI or MT with other treatments for CRPS types 1 and 2 were included. Six articles met the inclusion criteria and were classified from moderate to high quality. The total sample was composed of 171 participants with CRPS type 1. Three studies presented GMI with 3 components and three studies only used the MT. The studies were heterogeneous in terms of sample size and the disorders that triggered CRPS type 1. There were no trials that included participants with CRPS type 2. GMI and MT can improve pain in patients with CRPS type 1; however, there is not sufficient evidence to recommend these therapies over other treatments given the small size and heterogeneity of the studied population.

Dorsal root ganglion stimulation yielded higher treatment success rate for complex regional pain syndrome and causalgia at 3 and 12 months: a randomized comparative trial.

Animal and human studies indicate that electrical stimulation of dorsal root ganglion (DRG) neurons may modulate neuropathic pain signals. ACCURATE, a pivotal, prospective, multicenter, randomized comparative effectiveness trial, was conducted in 152 subjects diagnosed with complex regional pain syndrome or causalgia in the lower extremities. Subjects received neurostimulation of the DRG or dorsal column (spinal cord stimulation, SCS). The primary end point was a composite of safety and efficacy at 3 months, and subjects were assessed through 12 months for long-term outcomes and adverse events. The predefined primary composite end point of treatment success was met for subjects with a permanent implant who reported 50% or greater decrease in visual analog scale score from preimplant baseline and who did not report any stimulation-related neurological deficits. No subjects reported stimulation-related neurological deficits. The percentage of subjects receiving ≥50% pain relief and treatment success was greater in the DRG arm (81.2%) than in the SCS arm (55.7%, P < 0.001) at 3 months. Device-related and serious adverse events were not different between the 2 groups. Dorsal root ganglion stimulation also demonstrated greater improvements in quality of life and psychological disposition. Finally, subjects using DRG stimulation reported less postural variation in paresthesia (P < 0.001) and reduced extraneous stimulation in nonpainful areas (P = 0.014), indicating DRG stimulation provided more targeted therapy to painful parts of the lower extremities. As the largest prospective, randomized comparative effectiveness trial to date, the results show that DRG stimulation provided a higher rate of treatment success with less postural variation in paresthesia intensity compared to SCS.

A influência da suplementação de sulfato de condroitina na dor e nos aspectos funcionais associados à osteoartrose / Influence of chondroitin sulfate supplementation in pain and functional aspects associated with osteoarthritis

Introdução: A osteoartrose é a principal causa de limitação da funcionalidade e incapacidade nos idosos. Dentre os tratamentos farmacológicos está a suplementação com sulfato de condroitina. Objetivo: Realizar uma revisão sistemática sobre a influência do sulfato de condroitina na dor e aspectos funcionais associados à osteoartrose. Métodos: Foram utilizados os descritores "osteoarthritis" e "chondroitin". Os artigos foram selecionados de forma independente e cega, por dois pesquisadores. Foram incluídos somente ensaios clínicos primários, escritos na língua portuguesa, inglesa e espanhola entre 2005 a 2013. A escala PEDro foi utilizada como instrumento de avaliação. Resultados: Foram encontrados 1.916 estudos, permanecendo nove artigos para a análise. Dos nove analisados, quatro mostraram a eficácia da suplementação do sulfato de condroitina na redução da dor e da incapacidade funcional, enquanto cinco investigações não mostraram efeitos estatisticamente significantes. Conclusões: A influência do sulfato de condroitina na dor e aspectos funcionais na osteoartrose permanece questionável.

Introduction: Osteoarthritis is the leading cause of limitation of functionality and disability in the elderly. The supplementation with chondroitin sulfate is among the pharmacological treatments. Objective: To conduct a systematic review of the influence of chondroitin sulfate on pain and functional aspects associated with osteoarthritis. Methods: The keywords "osteoarthritis" and "chondroitin" were used. The articles were selected independently and blindly by two researchers. Only primary clinical trial, written in Portuguese, English and Spanish in the period between 2005 to 2013 were included. The PEDro scale was used as an evaluation tool. Results: A total of 1.916 studies with appropriate descriptors were found, and nine of these papers remained for analysis. Of these nine studies analyzed, four showed the effectiveness of supplementation of chondroitin sulfate in reducing pain and functional disability, while five studies showed no statistically significant effects. Conclusions: The influence of chondroitin sulfate in pain and functional aspects in osteoarthritis remains questionable.

Treatment of complex regional pain syndrome in adults: a systematic review of randomized controlled trials published from June 2000 to February 2012.

Complex regional pain syndrome (CRPS) is a disabling pain condition with sensory, motor and autonomic manifestations. Uncertainty remains about how CRPS can be effectively managed. We conducted a systematic review of randomized controlled trials (RCTs) for treatment and prophylactic interventions for CRPS published during the period 2000-2012, building on previous work by another group reviewing the period 1966-2000. Bibliographic database searches identified 173 papers which were filtered by three reviewers. This process generated 29 trials suitable for further analysis, each of which was reviewed and scored by two independent reviewers for methodological quality using a 15-item checklist. A number of novel and potentially effective treatments were investigated. Analysing the results from both review periods in combination, there was a steep rise in the number of published RCTs per review decade. There is evidence for the efficacy of 10 treatments (3× strong--bisphosphonates, repetitive transcranial magnetic stimulation and graded motor imagery, 1× moderate and 6× limited evidence), and against the efficacy of 15 treatments (1× strong, 1× moderate and ×13 limited). The heterogeneity of trialled interventions and the pilot nature of many trials militate against drawing clear conclusions about the clinical usefulness of most interventions. This and the observed phenomenon of excellent responses in CRPS subgroups would support the case for a network- and multi-centre approach in the conduct of future clinical trials. Most published trials in CRPS are small with a short follow-up period, although several novel interventions investigated from 2000 to 2012 appear promising.

Using graded motor imagery for complex regional pain syndrome in clinical practice: failure to improve pain.

BACKGROUND: There is good evidence from studies conducted in a single-centre research setting for the efficacy of graded motor imagery (GMI) treatment, a complex physiotherapy intervention, to reduce pain in long-standing complex regional pain syndrome (CRPS). However, whether GMI is effective in clinical practice is not established. AIM: To establish whether GMI is effective in clinical practice. METHODS: We undertook a prospective audit of GMI treatment at two UK centres with a special interest in the management of patients with CRPS. All patients received GMI, in conjunction with a range of other 'best practice' physical and psychological interventions. RESULTS: The patients' average pain intensities did not improve with treatment [centre 1: n = 20, pre-post numeric rating scale (NRS) difference 0.6 [confidence interval (CI) -0.3 to 1.5]; centre 2: n = 12, pre-post NRS difference 0.2 (CI: -0.9 to 1.2)]. Patients at centre 1 reported significant functional improvement. Improved performance on left/right judgement replicated in both centres seen in the clinical trials. CONCLUSIONS: The failure of our real-world implementation of GMI suggests that better understanding of both the GMI methodology and its interaction with other treatment methods is required to ensure that GMI research results can be translated into clinical practice. Our results highlight challenges with the translation of complex interventions for chronic pain conditions into clinical practice.

Motor cortex stimulation for trigeminal neuropathic or deafferentation pain: an institutional case series experience.

BACKGROUND: Trigeminal neuropathy is a rare, devastating condition that can be intractable and resistant to treatment. When medical treatment fails, invasive options are limited. Motor cortex stimulation (MCS) is a relatively recent technique introduced to treat central neuropathic pain. The use of MCS to treat trigeminal neuropathic or deafferentation pain is not widespread and clinical data in the medical literature that demonstrate efficacy are limited. METHOD: We retrospectively reviewed patients with trigeminal neuropathic or trigeminal deafferentation pain who were treated at the Oregon Health & Science University between 2001 and 2008 by 1 neurosurgeon using MCS. RESULTS: Eight of 11 patients (3 male, 8 female) underwent successful permanent implantation of an MCS system. All 8 patients reported initial satisfactory pain control. Three failed to experience continued pain control (6 months of follow-up). Five continued to experience long-term pain control (mean follow-up, 33 months). Average programming sessions were 2.2/year (all 8 patients) and 1.55/year (5 patients who sustained long-term pain control). Patients with anesthesia dolorosa or trigeminal deafferentation pain who had previously undergone ablative trigeminal procedures responded poorly to MCS. We encountered no perioperative complications. CONCLUSION: MCS is a safe and potentially effective therapy in certain patients with trigeminal neuropathy.

Stimulation of the medial plantar nerve for complex regional pain syndrome.

We describe a 47-year old male with complex regional pain syndrome II in the distribution of the medial plantar nerve following metatarsal fracture, which was treated with peripheral nerve stimulation. Using a new technique of nerve stimulation with a percutaneous-type electrode, the patient experienced sustained relief at 12 months follow-up. To our knowledge, this is the first report of peripheral neurostimulation effectively managing pain for the medial plantar nerve.

Peripheral median nerve stimulation for the treatment of iatrogenic complex regional pain syndrome (CRPS) type II after carpal tunnel surgery.

We report on the use and follow-up of direct peripheral nerve stimulation of the median nerve for the treatment of iatrogenic complex regional pain syndrome (CRPS). A 56-year-old woman presented with CRPS type II in the right forearm and hand, which had started after multiple carpal tunnel surgeries and had lasted for 2 years. The visual analogue scale (VAS) score was 8-10 out of 10. After a successful 15-day trial of median nerve peripheral nerve stimulation via a quadripolar lead in the right carpal tunnel space, an implantable pulse generator was inserted in the right infraclavicular space. The VAS score decreased to 1-2 out of 10 and the patient regained the ability to sleep. After 36 months of follow-up, the patient was still experiencing good pain relief without other treatment. We conclude that peripheral nerve stimulation is easy to use in pain management and could offer a valid treatment option for iatrogenic CRPS type II.

Maladaptive homeostatic plasticity in a rodent model of central pain syndrome: thalamic hyperexcitability after spinothalamic tract lesions.

Central pain syndrome (CPS) is defined as pain associated with a lesion of the CNS and is a common consequence of spinal cord injuries. We generated a rodent model of CPS by making unilateral electrolytic or demyelinating lesions centered on the spinothalamic tract in rats. Thermal hyperalgesia and mechanical allodynia occurred in both hind paws and forepaws by 7 d postlesion and were maintained >31 d. Field potentials in the ventral posterior lateral nucleus (VPL) in thalamic brain slices from lesioned animals displayed an increased probability of burst responses. Ethosuximide, a T-type calcium channel blocker, eliminated busting in lesioned thalamic slices and attenuated lesion-induced hyperalgesia and allodynia. We conclude that CPS in this model results from an increase in the excitability of thalamic nuclei that have lost normal ascending inputs as the result of a spinal cord injury and suggest that ethosuximide will relieve human CPS by restoring normal thalamic excitability.

Mirror visual feedback alleviates deafferentation pain, depending on qualitative aspects of the pain: a preliminary report.

OBJECTIVES: Following lesions in somatosensory pathways, deafferentation pain often occurs. Patients report that the pain is qualitatively complex, and its treatment can be difficult. Mirror visual feedback (MVF) treatment can improve deafferentation pain. We sought to classify the qualities of the pain in order to examine whether the potential analgesic effect of MVF depends on these qualities. METHODS: Twenty-two patients with phantom limb pain, or pain related to spinal cord or nerve injury, performed a single MVF procedure. Before and after the MVF procedure, we evaluated phantom limb awareness, movement representation of the phantom or affected/paralysed limb, pain intensity on an 11-point numerical rating scale (0-10) and the qualities of the pain [skin surface-mediated (superficial pain) vs deep tissue-mediated (deep pain)] using lists of pain descriptors for each of the two categories. RESULTS: Fifteen of the patients perceived the willed visuomotor imagery of the phantom or affected/paralysed limb after the MVF procedure. In most of the patients, a reduction in pain intensity and a decrease in the reporting of deep-pain descriptors were linked to the emergence of willed visuomotor imagery. CONCLUSIONS: In this pilot study, we roughly classified the pain descriptor items into two types for evaluating the qualities of deafferentation pain. We found that visually induced motor imagery by MVF was more effective for reducing deep pain than superficial pain. This suggests that the analgesic effect of MVF treatment does depend on the qualities of the pain. Further research will be required to confirm that this effect is a specific consequence of MVF.

Mirror therapy in patients with causalgia (complex regional pain syndrome type II) following peripheral nerve injury: two cases.

OBJECTIVE: To describe the use of mirror therapy in 2 patients with complex regional pain syndrome type II following traumatic nerve injury. DESIGN: Two case reports. SUBJECTS: Two patients with complex regional pain syndrome type II. METHODS: Two patients received mirror therapy with the painful hand hidden behind the mirror while the non-painful hand was positioned so that, from the perspective of the patient, the reflection of this hand was "superimposed" on the painful hand. Pain was measured with a visual analogue scale. RESULTS: The first case had developed a severe burning and constant pain in the hand due to a neuroma. In this patient, a strong reduction in pain was found during and immediately after mirror therapy. As a result, the patient was able to perform active exercises that were previously too painful. However, despite the pain relief during and directly after the exercises, the overall level of pain did not decrease. The second patient also had severe burning pain following a glass injury. In this patient, repeated mirror therapy for a 3-month period strongly decreased pain due to causalgia. CONCLUSION: The presented cases demonstrate that the use of mirror therapy in patients with causalgia related to a neuroma is worthy of further exploration as a potential treatment modality in patients with causalgia.

Somatosensory cortex stimulation for deafferentation pain.

Functional neuroimaging has demonstrated that a relationship exists between the intensity of deafferentation pain and the degree of deafferentation-related reorganization of the primary somatosensory cortex. It has also revealed that this cortical reorganization can be reversed after the attenuation of pain. Deafferentation pain is also associated with hyperactivity of the somatosensory thalamus and cortex. Therefore, in order to suppress pain, it seems logical to attempt to modify this deafferentation-related somatosensory cortex hyperactivity and reorganization. This can be achieved using neuronavigation-guided transcranial magnetic stimulation (TMS), a technique that is capable of modulating cortical activity. If TMS is capable of suppressing deafferentation pain, this benefit should be also obtained by the implantation of epidural stimulating electrodes over the area of electrophysiological signal abnormality in the primary somatosensory cortex. The first studies demonstrated a statistically significant pain suppression in all patients and a clinically significant pain suppression in 80% of them. This clinical experience suggests that somatosensory cortex stimulation may become a neurophysiology-based new approach for treating deafferentation pain in selected patients. In this chapter, we review the relevant recent reports and describe our studies in this field.

A retrospective analysis of reasons for reoperation following initially successful peripheral nerve stimulation.

OBJECT: The authors investigated the causes for surgical reexploration in patients with complex regional pain syndrome Type II who received initial relief of pain from implantation of a peripheral nerve stimulator (PNS). METHODS: The authors reviewed the charts of 11 consecutive patients who underwent a total of 27 PNS-related operations at one institution. Duration of follow up ranged from 5 days to more than 24 months. Of 11 patients who received PNS implants, seven (64%) required one or more additional surgeries to relocate the PNS because initial pain relief following stimulation was lost and not restored by changing pulse generator settings. Loss of analgesia was attributed to migration of the sutured electrode strip paddle (nine [33%] of 27 surgeries), infection (four [15%] of 27), and the need for placement in an alternative location (three [11%] of 27). CONCLUSIONS: Although infection is attributable to surgical technique, most complications requiring repeated surgery (nine [33%] of 27) are caused by equipment design. Changes in PNS design or in implantation technique might substantially reduce the need for reoperation after PNS implantation.