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.

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.

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.

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.

Thalamic sensory relay nucleus stimulation for the treatment of peripheral deafferentation pain.

We applied chronic deep brain stimulation (DBS) of the thalamic nucleus ventralis caudalis (Vc) for the treatment of peripheral deafferentation pain. The subjects included 11 cases of phantom limb pain and 7 of root or nerve injury pain without phantom sensation. In the phantom limb pain patients, the spike density markedly increased in the same area of the Vc where microstimulation induced paresthesia in the part with phantom sensation. Reorganization of the receptive field representation within the Vc was also demonstrated by microrecording and microstimulation. In the root or nerve injury pain patients with severe allodynia and without phantom sensation, oscillating neural hyperactivity appeared when the allodynia was induced during single-cell recording in the Vc. In both groups stimulation of these areas with the DBS electrode was useful for achieving pain reduction. Inhibition of spinothalamic tract neurons, restoration of the original receptive field representation and modulation of thalamocortical rhythmic oscillations are proposed to play important roles in a possible mechanism of Vc-DBS for the treatment of deafferentation pain.

Spinal cord stimulation in complex regional pain syndrome and refractory neuropathic back and leg pain/failed back surgery syndrome: results of a systematic review and meta-analysis.

The drive for good quality evidence has highlighted the importance of well-conducted systematic reviews and meta-analyses that critically evaluate and grade studies for new or existing therapies. A systematic review and meta-analysis was performed to review the efficacy, safety, and cost effectiveness of spinal cord stimulation (SCS) in complex regional pain syndrome (CRPS) and refractory neuropathic back and leg pain/failed back surgery syndrome (FBSS). The results support the use of SCS in patients with refractory neuropathic back and leg pain/FBSS (Grade B evidence) and CRPS type I (Grade A evidence)/type II (Grade D evidence). SCS not only reduces pain, improves quality of life, reduces analgesic consumption, and allows some patients to return to work, with minimal significant adverse events, but may also result in significant cost savings over time.

Motor cortex stimulation for intractable pain.

Effective management of neuropathic pain is one of the more challenging endeavors for even the most experienced and skilled pain specialist. Pharmacological therapy is frequently ineffective and/or poorly tolerated, especially in elderly patients. Many if not most surgical procedures have yielded limited success in the treatment of these pain conditions. Motor cortex stimulation (MCS) has emerged as a promising technique for the management of pain in patients with difficult neuropathic and central pain conditions. Although MCS has proven most successful for patients with trigeminal neuropathic/deafferentation pain and central poststroke pain, other conditions are now emerging as potential targets for this therapy. Based on previous as well as ongoing work, it would appear that the future of MCS is indeed bright. Hopefully, as work continues in this area, investigators will be able to develop a better understanding of the mechanisms underlying this modality and be able to further refine the technique of MCS. It is also possible that with the use of noninvasive tools such as transcranial magnetic stimulation, practitioners will be able to predict with accuracy which patients are likely to respond favorably to MCS.

Deep brain stimulation for the treatment of various chronic pain syndromes.

OBJECT: Electrical intracerebral stimulation (also referred to as deep brain stimulation [DBS]) is a tool for the treatment of chronic pain states that do not respond to less invasive or conservative treatment options. Careful patient selection, accurate target localization, and identification with intraoperative neurophysiological techniques and blinded test evaluation are the key requirements for success and good long-term results. The authors present their experience with DBS for the treatment of various chronic pain syndromes. METHODS: In this study 56 patients with different forms of neuropathic and mixed nociceptive/neuropathic pain syndromes were treated with DBS according to a rigorous protocol. The postoperative follow-up duration ranged from 1 to 8 years, with a mean of 3.5 years. Electrodes were implanted in the somatosensory thalamus and the periventricular gray region. Before implantation of the stimulation device, a double-blinded evaluation was carefully performed to test the effect of each electrode on its own as well as combined stimulation with different parameter settings. The best long-term results were attained in patients with chronic low-back and leg pain, for example, in so-called failed-back surgery syndrome. Patients with neuropathic pain of peripheral origin (such as complex regional pain syndrome Type II) also responded well to DBS. Disappointing results were documented in patients with central pain syndromes, such as pain due to spinal cord injury and poststroke pain. Possible reasons for the therapeutic failures are discussed; these include central reorganization and neuroplastic changes of the pain-transmitting pathways and pain modulation centers after brain and spinal cord lesions. CONCLUSIONS: The authors found that, in carefully selected patients with chronic pain syndromes, DBS can be helpful and can add to the quality of life.

On the relation between sensory deafferentation, pain and thalamic activity in Wallenberg's syndrome: a PET-scan study before and after motor cortex stimulation.

Decrease of thalamic blood flow contralateral to neuropathic pain has been described by several groups, but its relation with sensory deafferentation remains unclear. Here we report one instance where the thalamic effects of sensory deafferentation could be dissociated from those of neuropathic pain. A 50-year-old patient underwent a left medullary infarct leading to right-sided thermal and pain hypaesthesia up to the third right trigeminal division, as well as in the left face. During the following months the patient developed neuropathic pain limited to the left side of the face. Although the territory with sensory loss was much wider in the right (non painful) than in the left (painful) side of the body, PET-scan demonstrated significant reduction of blood flow in the right thalamus (contralateral to the small painful area) relative to its homologous region. After 3 months of right motor cortex stimulation the patient reported 60% relief of his left facial pain, and a new PET-scan showed correction of the thalamic asymmetry. We conclude that thalamic PET-scan hypoactivity contralateral to neuropathic pain does not merely reflect deafferentation, but appears related to the pain pathophysiology, and may be normalized in parallel with pain relief. The possible mechanisms linking thalamic hypoactivity and pain are discussed in relation with findings in epileptic patients, possible compensation phenomena and bursting thalamic discharges described in animals and humans. Restoration of thalamic activity in neuropathic pain might represent one important condition to obtain successful relief by analgesic procedures, including cortical neurostimulation.

Bilateral cortical stimulation for deafferentation pain after spinal cord injury. Case report.

The relief of intractable pain after spinal cord injury (SCI) is very difficult to obtain, even with dorsal root entry zone lesioning, spinal cord stimulation, and thalamic stimulation. Using bilateral motor cortex stimulation (MCS) the authors successfully treated a woman who experienced deafferentation pain 4 years after sustaining an SCI. To the authors' knowledge, this is the first report of bilateral MCS for pain relief after SCI. The success they achieved using this method indicates that MCS could be a new treatment option for deafferentation pain following SCI.