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.
Currently available central nervous system treatment strategies are often insufficient in management of peripheral neuropathic pain, prompting a resurgence of neuromodulation focused on peripheral ...pain. A new peripheral nerve stimulation device was investigated in a prospective, randomized, double blind, crossover study, looking specifically at efficacy and safety, with Food and Drug Administration oversight.
Prospective, multicenter, randomized, double-blind, partial crossover study to assess safety and efficacy. After IRB approval, patients were enrolled, implanted, and then followed for three months to assess efficacy and one year for safety based on Food and Drug Administration guidance.
One hundred forty-seven patients were consented and screened for the study. Thirty-five did not meet inclusion or exclusion criteria. Ninety-four patients were implanted and then randomized to the treatment (45) or the Control group (49). The primary efficacy endpoint, three months after randomization to treatment, demonstrated that patients receiving active stimulation achieved a statistically significantly higher response rate of 38% vs. the 10% rate found in the Control group (p = 0.0048). Improvement in pain was statistically significant between the randomized groups, with the Treatment group achieving a mean pain reduction of 27.2% from Baseline to Month 3 compared to a 2.3% reduction in the Control group (p < 0.0001). During the partial crossover period, patients again demonstrated statistically significant improvement in pain relief with active stimulation compared to baseline. Further, the Treatment group had significantly better improvement than the Control group in secondary measures including but not limited to quality of life and satisfaction. Safety, assessed throughout the trial and with follow-up to one year, demonstrated no serious adverse events related to the device. All device-related adverse events were minor and self-limiting.
The novel peripheral nerve stimulation device is a safe and effective treatment strategy to address neuropathic pain of peripheral nerve origin.
The Neuromodulation Appropriateness Consensus Committee (NACC) of the International Neuromodulation Society (INS) evaluated evidence regarding the safety and efficacy of neurostimulation to treat ...chronic pain, chronic critical limb ischemia, and refractory angina and recommended appropriate clinical applications.
The NACC used literature reviews, expert opinion, clinical experience, and individual research. Authors consulted the Practice Parameters for the Use of Spinal Cord Stimulation in the Treatment of Neuropathic Pain (2006), systematic reviews (1984 to 2013), and prospective and randomized controlled trials (2005 to 2013) identified through PubMed, EMBASE, and Google Scholar.
Neurostimulation is relatively safe because of its minimally invasive and reversible characteristics. Comparison with medical management is difficult, as patients considered for neurostimulation have failed conservative management. Unlike alternative therapies, neurostimulation is not associated with medication-related side effects and has enduring effect. Device-related complications are not uncommon; however, the incidence is becoming less frequent as technology progresses and surgical skills improve. Randomized controlled studies support the efficacy of spinal cord stimulation in treating failed back surgery syndrome and complex regional pain syndrome. Similar studies of neurostimulation for peripheral neuropathic pain, postamputation pain, postherpetic neuralgia, and other causes of nerve injury are needed. International guidelines recommend spinal cord stimulation to treat refractory angina; other indications, such as congestive heart failure, are being investigated.
Appropriate neurostimulation is safe and effective in some chronic pain conditions. Technological refinements and clinical evidence will continue to expand its use. The NACC seeks to facilitate the efficacy and safety of neurostimulation.
Abstract
Objective
To conduct a systematic literature review of peripheral nerve stimulation (PNS) for pain.
Design
Grade the evidence for PNS.
Methods
An international interdisciplinary work group ...conducted a literature search for PNS. Abstracts were reviewed to select studies for grading. Inclusion/exclusion criteria included prospective randomized controlled trials (RCTs) with meaningful clinical outcomes that were not part of a larger or previously reported group. Excluded studies were retrospective, had less than two months of follow-up, or existed only as abstracts. Full studies were graded by two independent reviewers using the modified Interventional Pain Management Techniques–Quality Appraisal of Reliability and Risk of Bias Assessment, the Cochrane Collaborations Risk of Bias assessment, and the US Preventative Services Task Force level-of-evidence criteria.
Results
Peripheral nerve stimulation was studied in 14 RCTs for a variety of painful conditions (headache, shoulder, pelvic, back, extremity, and trunk pain). Moderate to strong evidence supported the use of PNS to treat pain.
Conclusion
Peripheral nerve stimulation has moderate/strong evidence. Additional prospective trials could further refine appropriate populations and pain diagnoses.
Abstract
Objective
To conduct a systematic literature review of dorsal root ganglion (DRG) stimulation for pain.
Design
Grade the evidence for DRG stimulation.
Methods
An international, ...interdisciplinary work group conducted a literature search for DRG stimulation. Abstracts were reviewed to select studies for grading. General inclusion criteria were prospective trials (randomized controlled trials and observational studies) that were not part of a larger or previously reported group. Excluded studies were retrospective, too small, or existed only as abstracts. Studies were graded using the modified Interventional Pain Management Techniques–Quality Appraisal of Reliability and Risk of Bias Assessment, the Cochrane Collaborations Risk of Bias assessment, and the US Preventative Services Task Force level-of-evidence criteria.
Results
DRG stimulation has Level II evidence (moderate) based upon one high-quality pivotal randomized controlled trial and two lower-quality studies.
Conclusions
Moderate-level evidence supports DRG stimulation for treating chronic focal neuropathic pain and complex regional pain syndrome.
Complex regional pain syndrome (CRPS) presents a therapeutic challenge due to its many presentations and multifaceted pathophysiology. There is no approved treatment algorithm and clinical ...interventions are often applied empirically. In cases of CRPS where symptoms are localized to an extremity, a targeted treatment is indicated. We describe the use of intrathecal bupivacaine monotherapy, delivered through a retrograde catheter, in the treatment of CRPS affecting the lower extremity. The patient, a 57-year-old woman with a history of failed foot surgery, was seen in our office after 2 years of ineffective treatments with local blocks and neurolytic procedures. We advanced therapy to moderately invasive procedures with an emphasis on neuromodulation. A combined central and peripheral stimulation technique that initially provided 75% pain relief, failed to provide lasting analgesia. We proceeded with an intrathecal pump implant. Based on the results of dorsal root ganglion (DRG) mapping, L5-S1 was identified as the optimal target for therapy and a retrograde catheter was placed at this level. Various intrathecal medications were tested individually. An intrathecal morphine trial was ineffective (visual analog scale VAS 7), while intrathecal clonidine provided excellent pain relief (VAS 0) that was limited by severe side effects. Bupivacaine provided 100% analgesia with tolerable side effects (lower extremity weakness and minor bladder incontinence) and was selected for intrathecal infusion. After 14 months, bupivacaine treatment continued to control pain exacerbations. We conclude that CRPS patients benefit from early identification of the predominant underlying symptoms and a targeted treatment with moderately invasive techniques when less invasive techniques fail.
Intrathecal bupivacaine, bupivacaine monotherapy, retrograde catheter, complex regional pain syndrome (CRPS), dual stimulation, dosal root ganglion (DRG) testing.
Improved intrathecal (IT) pump technology is increasing the accuracy of IT opioid bolus dosing and promising advances in pain therapy. Opioid bolus dosing can be used with a minimal continuous ...infusion or it can function as the sole therapy. Bolus-only dosing is characterized by minimal use of opioid (often less than 1 mg of IT morphine). It achieves adequate pain control while reducing tolerance and possibly opioid-induced hyperalgesia. It may prevent receptor saturation, and provide a "washing out" of the opioid receptor that prevents the observed dose escalation resulting from continuous infusions. With new bolus dosing possibilities, IT pumps can be used earlier in the treatment algorithm instead of being a late-stage treatment for patients who responded poorly to conservative treatments. We hypothesize that morphine bolus-only IT dosing will have comparable adverse effect rates, and possibly increased safety as compared to the more conservative continuous delivery method. We further predict that bolus-only delivery will provide better therapy satisfaction, improved functional scores, lower 24 hour opioid dose, and less dose escalation.
This was a sub-analysis of the ACCURATE clinical trial that evaluated the accuracy and necessity of targeting paresthesia coverage of painful areas with dorsal root ganglion (DRG) stimulation vs. ...tonic spinal cord stimulation (SCS).
On diagrams of the torso and lower limbs, subjects marked where they felt pain at baseline and paresthesias at three months postimplant. Seventy-five subjects (41 DRG and 34 SCS) with diagrams of sufficient quality were scanned, digitized, and included in this analysis. Subject completed diagrams were digitized and superimposed with a grid of 1398 squares. Quantification of the percentage of bodily areas affected by pain and stimulation induced paresthesias was performed.
The percent of painful areas covered by paresthesia was significantly lower for DRG subjects than for SCS subjects (13% vs. 28% of the painful regions, p < 0.05), possibly because significantly more DRG subjects felt no paresthesia during stimulation when compared to SCS subjects (13/41 DRG vs. 3/34 SCS) (p < 0.05). The amount of paresthesia produced outside the painful areas (unrequired paresthesia) was significantly lower in DRG subjects than that of SCS subjects. On average, the percent of unrequired paresthesia was only 20% of the subjects' total painful body surface area in the DRG group compared to 210% in the SCS group (p < 0.01).
The results of this ACCURATE study sub-analysis show that DRG stimulation produces paresthesias, on average, that are less frequent, less intense, with a smaller footprint on the body and less dependent on positional changes.
Chronic upper extremity pain (UEP) has complex etiologies and is often disabling. It has been shown that 10 kHz SCS can provide paresthesia-free and durable pain relief in multiple pain types and ...improve the quality of life of patients.
To gain additional evidence on the safety and effectiveness of 10 kHz SCS for the treatment of chronic UEP.
It was a prospective, multicenter, and observational study. The study was registered on ClinicalTrials.gov prospectively (clinical trial identifier: NCT02703818).
Multicenter.
A total of 43 subjects with chronic UEP of ≥5 cm (on a 0-10 cm visual analog scale; VAS) underwent a trial of 10 kHz SCS, and subjects with ≥40% pain relief received a permanent implant. All subjects had upper limb pain at baseline, while some had concomitant shoulder or neck pain. Subject outcomes were assessed for 12 months, and the primary outcome was the responder rate (percentage of subjects experiencing ≥50% pain relief from baseline) at three months.
Thirty-eight subjects successfully completed the trial (88.3% success rate), 33 received permanent implants (five withdrew consent), and 32 had device activation (per protocol population). There were no paresthesias or uncomfortable changes in stimulation related to changes in posture during the study and there were no neurological deficits. Responder rates at 12 months for upper limb, shoulder, and neck pain in per protocol population (N=32) were 78.1%, 85.2%, and 75.0%, respectively. At 12 months, 84.4% of subjects were satisfied or very satisfied with 10 kHz SCS, and 38.7% either reduced or eliminated opioid usage.
This study further supports the effectiveness of 10 kHz SCS for chronic UEP treatment and documents the safety profile of the therapy.
NCT02703818.
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