2.4. Sample size calculation and analysis populations
Sample size was determined based on the planned noninferiority test for the composite safety and effectiveness primary end point of treatment success. Treatment success was defined as ≥50% reduction in the visual analog scale (VAS) score in the primary area of pain during both trial and the 3-month visits with no incidence of stimulation-induced neurological deficits. Pilot data with 8 CRPS subjects and 22 causalgia subjects indicated that the success rate of DRG, defined as a 50% reduction in pain intensity, was 87% for CRPS subjects and 77% for causalgia subjects. Thus, an observed success rate at of least 15% above the 50% rate reported for SCS subjects was expected.14,28 Accounting for 15% attrition, an estimated 152 subjects (76 subjects in each arm) would provide greater than 85% power to test the primary end point hypothesis with a noninferiority margin of 10%.
The primary, secondary, and tertiary effectiveness analyses were based on the modified intention-to-treat (MITT) population including all randomized subjects who participated in the trial procedure (73 in each group). The MITT population was based on standard intention-to-treat principles, wherein subjects were analyzed based on their initial randomized treatments. The binary composite end points for success included subjects who failed the trial evaluation and exited the study as treatment failures. Safety data tabulations are based on the intention-to-treat analysis set including all randomized subjects (76 in each group).
2.5. Data collection and general statistical methods
Patient demographics and medical history were collected at baseline. At baseline and at each study visit, physical and neurological examinations, along with medication utilization, were recorded by study staff. Pain intensity was measured at baseline and at each study visit using the 100-mm visual analog scale (VAS), ranging from 0 (no pain) to 100 (worst imaginable pain) where higher scores represent greater pain severity. At baseline and each study visit, assessments of quality of life, psychological disposition, and experiential factors (measures described in detail below) were completed. All adverse events (AEs) through 12 months were reported and the occurrence of any stimulation-related neurological deficits was documented.
Descriptive statistics are presented as number of subjects, mean, SD, median, and range for all continuous variables and the number and percentage of subjects for categorical variables. As stipulated by the protocol and with the exception of the primary end point analysis, DRG stimulation and SCS were compared using a 2-sample t test (or Wilcoxon rank-sum test) for continuous outcomes and Pearson χ2 test (or Fisher exact test) for categorical outcomes. Choice of parametric or alternative tests was based on the data distributions for each measure, and the test used is reported in the results. Two-sided confidence intervals are also provided for certain outcome measures of interest to assess differences between the treatment arm and the control arm.
2.6. Primary composite end point
The predefined primary composite end point of the study was treatment success rates for the DRG subjects compared to the SCS subjects. To be considered a treatment success (1) a subject had a successful trial reporting ≥50% reduction in VAS score from baseline to the end of the trial phase, (2) reported a VAS score at 3 months that was reduced from preimplant baseline by ≥50%, and (3) did not experience a stimulation-related neurological deficit during either the trial phase or after permanent implant. A stimulation neurological deficit, different from AEs, was defined as a measurable 2-point worsening on the in-clinic sensory and motor neurological examination, within the appropriate concordant anatomy, that was induced by stimulation and subsided in the absence of stimulation for at least 24 hours. Sensory and motor examinations were conducted by the physician and rated as 2 (normal function), 1 (decreased function), or 0 (abnormal function); a score of 0 would indicate neurological deficit. No neurological deficits, as defined, were recorded for any subjects in either arm of the study. In addition, if a subject withdrew from the study due to a device-, procedure-, or stimulation-related AE, the subject was treated as a failure in the primary end point analysis.
As prespecified, the primary end point analyzed the success rate between the two treatment arms using Blackwelder methods for testing noninferiority between 2 proportions at a one-sided significance of 0.05.3 The noninferiority margin was set at 10%. If noninferiority of the primary end point was achieved, a superiority test was performed at a one-sided significance level of 0.025.
2.7. Secondary end point
2.7.1. Positional effects on paresthesia intensity
Paresthesia intensity, a prespecified secondary end point, was assessed at 3 months. Paresthesia intensity was rated by subjects using a previously published paresthesia intensity rating scale.16 Subjects rated the intensity of their perception of paresthesia, while upright and supine, on an 11-point numeric rating scale from 0 representing “No feeling” to 10 “Very intense.” Perceived paresthesia intensity difference between supine and upright positions was calculated and averaged across each group This end point was evaluated at a 2-sided significance level of 0.05.
2.8. Other end points
The Short-Form-36 (SF-36) is a self-reported health-related quality-of-life scale with 36 questions that yield scores on 8 dimensions of quality of life including physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health.27,29 These 8 dimensions also are combined to provide 2 summary scales for physical health (Physical Component Summary) and mental health (Mental Component Summary). Improvements on the SF-36 scale are represented by increased scores. Within- and between-group improvements were examined using the calculated change from baseline for each subscale or summary scales.
2.8.2. Profile of mood states
The profile of mood states (POMS) scale is a 65-item, 5-point Likert scale that measures mood states overall (total mood disturbance) as well as for 6 domains: tension, depression, anger, vigor, fatigue, and confusion. Higher scores indicate more negative mood states except for the vigor domain where higher scores indicate increased vigor.6 Within- and between-group improvements were examined using the calculated change from baseline for each domain and the total POMS score.
2.8.3. Brief pain inventory
The brief pain inventory (BPI) measures pain severity in the last 24 hours on a numeric pain rating scale from 0 “No pain” to 10 “Pain as bad as you can imagine,” and interference due to pain from 0 “Does not interfere” to 10 “Completely interferes.”5 The interference score was calculated as the mean of the interference items, and 2 subscales for the activity dimension and the affective dimensions of interference were tabulated. Within- and between-group improvements were examined using the calculated change from baseline for the pain and interference scales and for each interference subscale.
2.8.4. Subject satisfaction
Subjects completed a satisfaction scale at the end of trial phase and at 3, 6, and 12 months. Subjects rated satisfaction with pain relief and the therapy in general on an 11-point numeric rating scale with 0 indicating “Not Satisfied” and 10 indicating “Very Satisfied.” Subjects rated the likelihood of undergoing the therapy again on an 11-point numeric rating scale with 0 indicating “Not Likely” and 10 indicating “Very Likely.” Finally subjects rated the their subjective change in pain since baseline on a 7 point scale ranging from “Much Worse” to “Much Better.” Ratings were treated as interval data and summarized with descriptive statistics of central tendency.
2.8.5. Stimulation specificity
Stimulation specificity was evaluated to determine the extent to which paresthesia was felt by subjects in anatomical regions that were not painful at baseline. The pain and paresthesia diagram forms had identical diagrams of the human body on which subjects marked where they felt pain and paresthesia. The baseline pain diagrams completed by the subjects were compared to the subjects' paresthesia maps completed at the end of trial phase and at 3 months postimplant. Subjects were categorized based on the presence or absence of one or more paresthesia areas at follow-up that were not coincident with a pain area at baseline.
2.8.6. Percentage change in visual analog scale
The percentage of change in VAS score from baseline to each scheduled follow-up was computed for each subject and inspected using descriptive statistics and confidence intervals. Missing data were not imputed for this analysis; only subjects with VAS scores at baseline and follow-up were included in the analysis.
2.9. Safety analysis
Adverse events were collected and tabulated at all scheduled or unscheduled visits during the study. An AE was defined as any unfavorable and/or unintended sign, symptom or disease temporarily associated with the use of the implanted device, whether or not related to the device. A serious adverse event (SAE) was defined as any AE that is immediately life threatening; results in significant, persistent, or permanent disability; necessitates invasive intervention to prevent permanent impairment or death; results in the need for a 24-hour hospital stay or prolongation of a hospital stay; or results in death. Adverse event and SAE rates are expressed as the number of patients divided by the population at risk for each group (n = 76) through the 12-month study visit. All AEs reported were reviewed by an independent event committee that coded and adjudicated each event with regard to seriousness and relatedness to the implant procedure, device, and/or stimulation therapy.
3.1. Patient accounting
See CONSORT diagram for full accounting (Fig. 2). Briefly, 320 subjects were consented and enrolled in the study from 22 investigational sites. Of these subjects, 168 were excluded for screen failures because they failed to meet the study's inclusion or exclusion criteria with the majority failing to meet the diagnostic criteria for inclusion. The remaining 152 subjects were enrolled and randomized to either the DRG or the SCS arm (76 in each arm). After randomization, 3 subjects from each group did not continue to the trial evaluation phase. Subjects who failed the success criterion at the end of the trial phase were exited from the study and considered treatment failures for composite end point analyses. A total of 61 DRG subjects and 54 SCS subjects met the success criteria at the end of their trial phase and continued to permanent implant. By the 12-month visit, 55 DRG subjects and 50 SCS subjects had evaluable data.
On average, each active study site randomized 3 subjects (range 0, 9) to each arm of the study. At any one site, the maximum number of randomized subjects was 11% (17/152) of the MITT population.
3.2. Baseline characteristics
The average age of subjects was 52.4 years in the DRG stimulation arm and 52.5 years in the SCS arm. There were slightly more females than males in both arms (51.3% for both arms). Race was predominantly white (94.7% and 92.1% for DRG and SCS, respectively). Average body mass index was 30.5 for DRG and 28.9 for SCS. The average duration of chronic lower limb pain was 7.5 years for the DRG arm and 6.8 years for the SCS arm. Comorbidities and medications taken for subject conditions were similar in both arms. Overall, no statistically significant differences were found among the baseline characteristics between treatment arms. See Table 4 for a detailed summary of baseline characteristics.
Similar distribution of CRPS (DRG: 44/76 [57.9%]; SCS: 43/76 [56.6%]) and causalgia (DRG: 32/76 [42.1%]; SCS: 33/76 [43.4%]) was reported between the arms. All CRPS subjects had sensory symptoms, 82/87 (94.3%) had motor trophic symptoms, 57/87 (65.5%) had vasomotor symptoms, and 58/87 (66.7%) had sudomotor or edema symptoms. A total of 79 of the 87 CRPS subjects had at least one symptom in each of 3 symptom categories documented at baseline; 8 CRPS subjects (3 in the DRG group and 5 in the SCS group) had one symptom in each of 2 symptom categories documented at the time of the baseline evaluation (sensory and motor). In the 8 subjects with only 2 secondary symptoms (sensory and motor) at enrollment, the medical monitor indicated that the reason that sudomotor or edema and vasomotor symptoms were not present at enrollment was a manifestation typically evident in the acute or early phase of the disease. The 8 patients who were enrolled in the study with only 2 symptoms documented had a range of 3 to 11 years of history of CRPS before enrollment. For subjects diagnosed with causalgia the injured nerves are documented in Table 5.
3.3. Primary composite end point
Figure 3 summarizes the primary composite end point results at 3 months, when the primary end point was ascertained, as well as over time through 12 months. No neurological deficits were reported during the study, so the rates of success at each time point include those subjects with a permanent implant who reported at least a 50% reduction in VAS from preimplant levels. Randomized subjects who did not proceed to permanent implant were considered treatment failures for this end point at each study visit. The proportion of subjects who achieved treatment success at 3 months in the DRG arm (81.2%; 56/69) was statistically greater than the SCS arm (55.7%; 39/70). The results demonstrated that DRG stimulation met not only noninferiority (P < 0.0001) but also statistical superiority (P < 0.0004). Long term, the proportion of subjects who achieved treatment success at 12 months in the DRG arm (74.2%; 49/66) also was greater than that in the SCS arm (53.0%; 35/66); these results demonstrated both noninferiority (P < 0.0001) and superiority (P < 0.0004) at the long-term follow-up.
Similar results were observed at 3 months when the primary end point was stratified by primary diagnoses. For CRPS, a greater proportion of DRG subjects (82.5%) met the primary end point at 3 months than SCS subjects (57.5%) (noninferiority, P < 0.001; superiority, P = 0.006). For causalgia, the proportion of subjects who met the primary end point was higher for DRG (79.3%) than for SCS (53.3%) (noninferiority, P = 0.001; superiority, P = 0.014).
3.4. Secondary end point
On average, DRG subjects experienced significantly less postural variation in perceived paresthesia intensity than the SCS subjects (P < 0.001) at 3 months. Dorsal root ganglion subjects reported a mean difference between supine and upright paresthesia intensity rating of −0.1 ± 1.6, and SCS subjects had a mean difference of 1.8 ± 3.0. These results persisted throughout the study (Fig. 4).
3.5. Other end points
Table 6 summarizes the SF-36 results. Both the DRG stimulation and SCS groups experienced improvements in SF-36 scores from baseline to 3 months (P < 0.05) and 12 months, with the one exception that the General Health scale was not significantly improved at 12 months in the SCS group (P > 0.05).
At 3 months, the change in the mental health dimension was statistically better for DRG stimulation subjects compared to SCS subjects (P = 0.0295). At 12 months, DRG subjects had statistically greater improvement on 3 scales: overall change in the physical component score (P = 0.04), general health (P = 0.03), and social functioning (P = 0.03) when compared to SCS subjects.
3.5.2. Profile of mood states
Both groups experienced improvements in all domains of the POMS from baseline to 3 months (P < 0.05). At 12 months, DRG subjects had statistically significant improvements in all scales (P < 0.05), and the SCS subjects had statistically significant improvements (P < 0.05) in all scales except for the depression and confusion scales compared to baseline.
Figure 5 presents the change in POMS scores through the 12-month visit. The changes in POMS scores from baseline to 3 months were statistically greater for DRG subjects than for SCS subjects for the Total Mood Disturbance scale (P = 0.0466) and the tension domain (P = 0.0430). Specifically, the Total Mood Disturbance at 3 months improved by a magnitude of 20.4 points (29.0 at baseline to 8.6 at 3 months) for DRG subjects, and only a magnitude of 14.7 points (25.6 at baseline to 10.9 at 3 months) for SCS subjects. These improvements in the Total Mood Disturbance and tension domain score for DRG subjects persisted to 12 months (P = 0.021 and P = 0.004, respectively). In addition, at 12 months, the depression (P = 0.004) and confusion (P = 0.020) domains also demonstrated statistically greater magnitudes of improvement for DRG subjects compared to the improvements for SCS subjects.
3.5.3. Brief pain inventory
As shown in Table 7, both groups experienced improvements in all of the BPI scales from baseline to 3 months (P < 0.05) and 12 months (P < 0.05). Between the 2 groups, improvements from baseline on the interference scale (treatment 4.2, control 3.0), the activity scale (treatment 4.5, control 3.4), and the affective scale (treatment 3.8, control 2.5) were statistically greater (P < 0.05) for DRG subjects compared to SCS subjects at 3 months. These results persisted to 12 months.
3.5.4. Subject satisfaction
The majority of patients in both groups reported high degrees of satisfaction (Table 8) for all 4 satisfaction items. However, no statistical significance was found between the groups for all items assessed (P > 0.05).
3.5.5. Stimulation specificity
At 3 months, SCS subjects were 2.3 times more likely to report feeling paresthesia in one or more nonpainful areas as DRG subjects (35.2% vs 15.3%, P = 0.0142). At 12 months postimplant, SCS subjects were 7.1 times more likely to report feeling paresthesia in one or more nonpainful areas as DRG subjects (38.8% vs 5.5%, P < 0001). The percent of subjects who reported that they felt paresthesia in only their painful region(s) at 3 and 12 months was 84.7% and 94.5% in the DRG group, and 64.8% and 61.2% in the SCS group.
3.5.6. Percentage change in visual analog scale
As shown in Table 9, DRG stimulation demonstrated a greater mean percent reduction in VAS scores than SCS (84.1% vs 70.9%, respectively) with the significant reduction persisting to 6 months and 12 months. Subjects using DRG reported mean VAS of 80.6 mm at baseline, which reduced to 13.1 mm at 3 months and remained low, at 15.0 mm, at 12 months. The subjects using SCS reported a baseline mean VAS of 80.7, 3-month mean VAS of 23.8 mm, and 12-month mean VAS of 26.5 mm.
3.6. Safety analysis
A total of 21 SAEs occurred in 19 subjects (8 DRG subjects and 11 SCS subjects). The rates of SAEs were 10.5% (8/76) in the DRG arm and 14.5% (11/76) in the SCS arm. The difference in the rate of SAEs between groups was not statistically different (P = 0.62). Two of the SAEs in the control group were adjudicated as definitely related to the implant procedure. Both events were infections that required device explant. There were no unanticipated SAEs or stimulation-induced neurological deficits at any time during the study. None of the subjects died.
Table 10 presents the rates of related AEs. Fifty two procedure-related events were reported by 35 patients (46.1%) in the DRG arm, and 29 procedure-related events were reported by 20 patients (26.3%) in the SCS arm, yielding a statistically significant difference between the groups (P = 0.018). Possible contributors to the differential rate of procedure-related AEs are the procedure times and number of leads. Procedure times for permanent implant averaged 107.2 minutes (±51.2) for DRG subjects and 75.7 minutes (±32.2) for SCS subjects. In addition, 16.4% (10/61) of DRG subjects were implanted with 3 or 4 leads, while all SCS subjects had 1 or 2 leads implanted. For both groups, the most frequently occurring procedure-related AE was pain at the incision sites with 7 events reported by 6 patients (7.9%) in the DRG arm and 5 events reported by 5 patients (6.6%) in the SCS arm.
For device-related AEs, 39 events were reported by 28 patients (36.8%) in the DRG arm and 24 events were reported by 20 patients (26.3%) in the SCS arm. No statistical difference was found between the groups (P = 0.22). The most frequently occurring device-related AE in the DRG arm was implantable pulse generator (IPG) pocket pain with 10 events reported by 10 patients (13.2%). On the other hand, the most frequently occurring device-related AE in the SCS arm was loss of stimulation due to lead migration with 8 events reported by 8 (10.5%) patients.
There was also no statistical difference between the groups for stimulation-related AEs (P = 0.8025). Ten events were reported by 8 patients (10.5%) in the DRG arm, and 10 events were reported by 10 patients (13.2%) in the SCS arm. The most frequently occurring stimulation-related AE for both groups was overstimulation with 3 events reported by 3 patients (3.9%) in the DRG arm and 5 events reported by 5 patients (6.6%) in the SCS arm.
This study represents the largest randomized controlled trial assessing DRG stimulation for the treatment of chronic, intractable pain associated with the diagnoses of CRPS or causalgia. Analysis of the primary end point revealed that subjects using DRG stimulation had a higher rate of treatment success (81.2%) compared with the treatment success rate for traditional SCS (56.7%). Furthermore, pain relief persisted through 12 months of follow-up and remained significantly lower for DRG subjects than for those using SCS. Subjects using DRG reported significantly less postural-related changes in paresthesia and showed larger improvements on measures of quality of life, functional status, and psychological disposition than subjects using SCS. The safety profile of the DRG stimulation device was similar to traditional SCS devices, with the exception of the rate of procedural events.
These results for DRG stimulation as a treatment of chronic neuropathic pain associated with CRPS and causalgia must be interpreted within the context of previous neurostimulation studies for this population. Treatment of chronic reflex sympathetic dystrophy with SCS, in combination with physical therapy, reduced pain to a greater degree than physical therapy alone14; mean VAS scores for implanted patients reduced to 3.5 cm on a 10-cm VAS scale after 6 months of SCS. A retrospective analysis of SCS for the treatment of CRPS reported a mean VAS of 5.6 cm over a mean follow-up time of 88 months.19 Mean VAS scores during SCS therapy in both these previous studies were higher, by a clinically meaningful margin10 than the VAS score of 13.1 mm and 15 mm reported by subjects treated with DRG stimulation in our study at 3 and 12 months. Similarly, Geurts et al.11 reported only a 50% pain reduction in an observational trial of SCS for CRPS.
A study using a heterogeneous population, including subjects with CRPS, reported that 68.4% of subjects were able to achieve ≥50% leg pain relief, and 60% of subjects achieved ≥50% pain relief for overall pain.21 A published case series of CRPS subjects reported that 71.4% of subjects achieved ≥50% pain relief after 6 months of DRG stimulation.28 In addition, a randomized trial comparing SCS to physical therapy for subjects with CRPS reported that 50% of subjects achieved at least 50% reduction in pain intensity.14 Here, we report an 84% reduction in pain for patients treated with DRG stimulation and that 81% of subjects achieved ≥50% pain relief. Furthermore, the optimal programming for DRG stimulation is still being developed; Table 2 shows that SCS and DRG parameters were quite different. Additional developments in optimized programming for DRG should improve clinical outcomes over time for this therapy. Taken together, we conclude that DRG stimulation provides better pain relief than traditional SCS.
Patients with CRPS and causalgia are difficult to treat with symptoms for 20% to 80% of CRPS I patients persisting for 1 year, even when treatment was considered successful.2 Surgical interventions such as joint denervation or neurolysis also have variable outcomes; approximately 20% of patients failed to report low pain intensity and improved activities of daily living 2 years after surgery.9 For patients with CRPS I or causalgia who do not achieve adequate pain management with conservative therapies, SCS provides an additional and reversible treatment option. Furthermore, DRG stimulation augments the patient experience by providing a therapy that is adaptable to each patient's individual pain profile through more precise anatomical targeting.
The pathways for sensory afferents into the central nervous system via the DRG are well documented.4,13 Anatomically, peripheral inputs associated with pain symptoms can be traced to relevant DRG at one or more spinal levels. Stimulation of the relevant DRG modifies pain signaling from the periphery for only the affected dermatomes. By contrast, SCS targets large dermatomal areas through stimulation of the dorsal column at anatomically defined spinal levels, and, as such, modifies ascending pathways for pain while also modulating collateral afferents in or near the medial lemniscus. Modulating pain signals from distal appendages with SCS typically requires that multiple dermatomes be captured–with paresthesias in the entire region. Our results showed that subjects treated with DRG stimulation had significantly less perceived stimulation sensation in nonpainful areas than subjects using SCS, while reporting better pain relief. This may indicate more precision targeting by virtue of the greater anatomical specificity with DRG stimulation.
The differences in collateral paresthesia may also be influenced by differences in programming parameters. Programming parameters were individualized for each subject's optimal experience. The resulting parameters were quite different between the 2 therapies (Table 2) with much lower amplitudes for DRG programming. This was expected from pilot work7 and because diffusion of energy by the cerebrospinal fluid is less influential at the DRG. The between-subjects design of this study prohibits a real comparison of the relationship between targeting, programming, and pain relief; more research is needed.
Chronic pain conditions, in general, are associated with disturbances in mood and physical and social functioning.1,22,24 The targeted pain relief provided by DRG stimulation in the ACCURATE study was also associated with additional benefits. After 3 months, subjects using DRG stimulation reported significantly greater improvements in total mood disturbance, as measured by the POMS, as well as larger improvements pain interference, affective disruption, and activity, as measured by the BPI. Moreover, by 12 months, subjects treated with DRG stimulation reported significantly larger improvements than SCS subjects for physical function, general health, and social function, as measured by the SF-36.
Despite the differences reported for treatment success, pain relief, and affective or functional outcomes, the majority of subjects were satisfied with their respective therapy, regardless of treatment group. While subjects using DRG stimulation reported a larger magnitude of change and there was a greater proportion of successful subjects with DRG stimulation, SCS subjects, as a group, did report significant improvements from baseline in all measured domains. The satisfaction results reported here reflect the improvements from preimplant baseline experienced by subjects.
The rate of AEs for DRG stimulation, through 12 months postimplant, was similar to that seen for the SCS-treated subjects in this study and in previous reports.17,20 Only 2 subjects had procedure-related SAEs; 2 infections in the SCS group that required explant. It is notable that the rate of nonserious procedure-related events was higher for the DRG stimulation group (46%) compared with the SCS group (26%). The higher rate of procedure-related events may be attributed to the differences in average procedure time and a greater number of leads placed for DRG some subjects, which may increase exposure to risk. It is expected that additional experience with DRG implantation will result in shorter procedure times and fewer procedure-related events.
There are limitations to this study that may affect the interpretation of the results. The calculated success rate was contingent upon subjects not only achieving 50% pain relief but also continuing in the study (dropouts were counted as failures). Therefore, the success rate could be influenced by factors associated with the lack of blinded treatments (eg, SCS subjects were less motivated to stay in the trial, uncontrolled differences in health care provider interactions). In addition, subjects were required to maintain a stable regimen of pain medications through 3 months only, and the long-term results after 3 months may be affected by medication changes. The SCS device also had limitations placed on the programming of the device so that the comparison between the devices was not confounded by unique SCS device programming features. In particular, the accelerometer function in the SCS device was disabled. If the accelerometer was enabled, the SCS group may have had less postural changes in perceived paresthesia intensity. In addition, the analysis of subjects who did and did not experience paresthesia when stimulation was on was confounded by the fact that the SCS device instruction for use requires the device to be programmed for subjects to receive paresthesia. In addition, the number of subjects who did not have paresthesia is very small, and this end point was not adequately powered to detect the difference in pain relief for subjects who reported feeling vs not feeling paresthesia.
In conclusion, CRPS I and causalgia, in their chronic forms, are difficult to treat with variable outcomes with conservative symptom management. Neuromodulation techniques, like SCS, may benefit many patients who have exhausted other therapy options. SCS, however, often has a limited ability to target discrete focal anatomical regions of pain, as is common in CRPS and causalgia. Dorsal root ganglion stimulation provides an effective alternative that provides precision stimulation targeting and improved patient outcomes.
Conflict of interest statement
All authors were paid by Spinal Modulation & St Jude Medical as investigators for the clinical trial. T. R. Deer is a consultant for Axonics, Bioness, Flowonix, Medtronic, Jazz, Nevro, St. Jude, and Saluda and has consulting or equity for Axonics and Bioness. T. R. Deer formerly had equity in Spinal Modulation and Nevro. R. M. Levy has served as a consultant for Bioness, BlueWind Medical, Boston Scientific, Flowonix, Medtronic, Microtransponder, Nevro, Saluda, Spinal Modulation, and St Jude Medical. R. M. Levy is or has been a minority shareholder in Saluda, Spinal Modulation, Bioness, Vertos, and Nevro. N. Mekhail formerly had a consultation agreement with spinal modulation to serve as medical monitor of the ACCURATE study. Currently, he is a consultant for St Jude Medical, Saluda medical, Stimwave, Medtronic neurological, and Flowonix inc. K. Amirdelfan is a consultant for St. Jude Medical, Nevro, Saluda, Nalu, and Biotronik. J. Pope is a consultant for Medtronic, NEVRO, St Jude, Flowonix, Jazz Pharmaceuticals, and Suture Concepts. T. Yearwood is a consultant for St Jude Medical, Boston Scientific, Nevro, Flowonix, and Neuronano; he serves as an officer for Meghan Medical. W. P. McRoberts serves or has served as a consultant for St Jude Medical, Medtronic, Nevro, Boston Scientific, Bioness, Vertiflex, and SPR. T. Davis has conducted research for Spinal Modulation, Vertiflex, Medtronic, Axsome, Nature Cell, and Halyard Health; has received fees for consulting, education, or speaking from St Jude Medical, Medtronic Restorative Therapies, Stryker, Vertiflex, DrChrono, and Tenex Health; and has ownership interests in Paradigm Spine <1%, LDR Holdings <1%, Alpha Diagnostics Neuromonitoring, and Broadway Surgical Institute. J. Scowcroft has served as a consultant for Boston Scientific. L. Kapural is a consultant for St Jude Medical, Nevro, Neuros, SPR Therapeutics, and Saluda. R. Paicius is a consultant for St Jude Medical, Nevro, and Boston Scientific. J. Kramer, Burton, Johnson, and Kristina Davis are employees of St. Jude Medical. The remaining authors have no conflicts of interest to declare.
This study was sponsored by Spinal Modulation, LLC, a wholly owned company of St. Jude Medical.
All authors contributed to the study design, data acquisition, and/or writing of this manuscript in accordance with the guidelines set forth by the International Coalition of Medical Journal Editors. T. R. Deer and R. M. Levy are co-primary authors with equal contributions to the work. In addition to the above, N. Mekhail served as an independent medical monitor of the study.
The authors thank Kaisa Kivilaid for statistical support and Angela Leitner for technical help on this project.
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Keywords:© 2017 International Association for the Study of Pain
Chronic pain; Neurostimulation; Complex regional pain syndrome; Causalgia; Dorsal root ganglion stimulation