Per the Budapest criteria, CRPS is a diagnosis characterized by pain that is disproportionate to the inciting event associated with abnormal sensory (allodynia), as well as vasomotor, sudomotor, and/or motor/trophic symptoms [23]. One RCT [6] and 11 observational studies [5, 10, 16, 24,25,26,27,28,29,30,31] described DRG-S for treatment of pain from CRPS (Table 1). The ACCURATE RCT [6] demonstrated that DRG-S was non-inferior (p < 0.0001) and superior (p < 0.0004) to traditional dorsal column SCS through 12 months of follow-up for lower extremity CRPS pain intensity. When the primary endpoint was assessed at 3 months (50% reduction in visual analog scale [VAS] from pre-implant levels), 56 of 69 (81.2%) participants receiving DRG-S achieved treatment success versus 39 of 70 (55.7%) participants receiving dorsal column SCS (statistical non-inferiority p < 0.0001, statistical superiority p < 0.0004). Similarly, 49 of 66 (74.2%) participants in the DRG-S cohort achieved the primary endpoint at 12 months versus 35 of 66 (53.0%) participants in the SCS cohort (statistical non-inferiority p < 0.0001, statistical superiority p < 0.0004). The DRG-S cohort also reported higher quality of life, functional status, and emotional functioning metrics compared to those receiving dorsal column SCS. Importantly, participants receiving DRG-S reported less postural variation of paresthesias and less non-specific, extraneous stimulation in non-painful areas compared to those receiving dorsal column SCS.

Findings from the pivotal ACCURATE trial are further supported by data from five prospective observational studies [5, 16, 24,25,26], four cases series [10, 27,28,29], and two case reports [30, 31]. In total, these observational studies comprised 148 participants with CRPS type I and 188 participants with CRPS type II. Huygen et al. [25] reported a multicenter, prospective study that enrolled participants with failed back surgery syndrome, peripheral neuropathy, and CRPS. Eleven CRPS type I participants (46.8%) and 13 CRPS type II (43.7%) participants reported pain relief at 12 months. Gravius et al. [24] conducted a prospective study on participants with CRPS type I, who achieved 61.3% pain reduction along with improved mood and sleep metrics at 3 months post-implant. Morgalla et al. [36] performed a prospective study that enrolled 62 participants with CRPS type II with 51 receiving permanent DRG-S. The study reported improvement in mean VAS scores (8.0–4.5), function (Brief Pain Inventory, 76–30; Pain Disability Index, 45–23), and mood (Beck Depression Inventory, 36–21) at 36-month follow-up. Liem et al. [5] reported that eight participants with CRPS type I with permanent DRG-S had reduced pain by 56% at 12 months. Knife et al. [16] studied the effects of DRG-S on quantitative sensory threshold (QST) testing in participants with CRPS type I, and reported improved warmth, tactile, and vibration QSTs along with normalization of pain sensory thresholds after DRG-S implant. These positive outcomes from prospective observational studies supporting DRG-S for CRPS are further reinforced by data from case series and reports [10, 27,28,29,30,31].

In summary, the evidence base for DRG-S for the treatment of CRPS type I or CRPS type II includes one RCT and 11 observational studies reporting outcomes between 3 and 36 months. There was low-quality GRADE evidence that DRG-S reduced pain and disability in participants with CRPS type I or CRPS type II. According to the GRADE approach, the evidence quality was initially rated as “moderate quality” evidence based on the ACCURATE trial [6]. With inclusion of observational studies, this was downgraded to “low quality” because of risk of bias, imprecision, and indirectness (Fig. 2 and Table 2). Furthermore, the participants in these studies were heterogenous. Aside from the ACCURATE trial, the sample size of participants in each study was low and underpowered to detect significant differences between the groups.

Risk of bias summary. Risk of bias scores for the single randomized controlled trial are displayed on the basis of the authors’ judgements of each item. Green signifies low risk of bias, red signifies high risk of bias, and yellow signifies unclear risk of bias

Painful diabetic neuropathy (PDN) is defined as a symmetric, length-dependent sensorimotor polyneuropathy attributable to metabolic and microvascular alterations as a result of chronic hyperglycemia exposure and cardiovascular risk covariates [43]. This can be a progressive and debilitating condition that can cause painful paraesthesias, with only one-third of patients typically achieving clinically significant pain relief from conventional therapy [44]. Neuromodulation interventions are becoming more common modalities utilized in the treatment of PDN [45,46,47]. Two retrospective studies [8, 48] and one case report [49] described DRG-S for treatment of PDN (Table 3).

Eldabe et al. [8] performed a retrospective study of ten participants with chronic intractable PDN who trialed DRG-S using up to four quadripolar percutaneous leads between L2 and L5. Of the seven patients who proceed to implantation, five patients followed to six months reported a mean VAS reduction of 49.4 mm, and four patients followed to twelve months reported a mean VAS reduction of 48.2 mm. Overall, this study reported a 70% success rate for trial-to-implant ratio and clinically significant pain relief in most patients followed to 12 months. Similarly, Falowski et al. [48] performed a retrospective analysis in which eight patients with chronic intractable peripheral neuropathy of the lower extremities underwent DRG-S. Two of these patients had PDN, with one achieving over 70% pain relief after bilateral L5 DRG lead placement after 6 weeks, and the other patient experiencing 100% pain relief after lead placement unilaterally at the left L4 and L5 levels. Finally, Chapman et al. [49] published a case report of a 61-year-old man with PDN and low back pain. He underwent a 7-day trial of unilateral DRG stimulation at the right T12 and S1, which allowed the untreated side to serve as a comparison. This resulted in significant pain relief in both feet and low back pain, with a VAS reduction from 8 to 1 cm for his back pain, and from 9 cm to 0 for his feet pain. This patient also had improvements in quality of life, physical function, emotional function, ambulation, skin color, and numbness in his feet.

In summary, the available evidence for DRG-S for PDN includes two retrospective case series and a case report, with study outcomes between 7 days and 12 months. Overall, there was very low-quality GRADE evidence that DRG-S reduced pain intensity for participants with PDN. Criteria that lowered the evidence level included study methodology limitations, indirectness due to varying patient diagnoses, and imprecision from small sample sizes.

One retrospective study [50] and two case series [48, 51] reported outcomes from DRG-S in participants with focal neuropathy or mononeuropathy (Table 4). Kretzschmar et al. [50] reported that 23 of 27 participants with traumatic upper extremity and lower extremity injury underwent DRG-S implant after a successful DRG-S trial providing greater than 50% pain relief. At 36 months follow-up, pain intensity was reduced by a mean of 73%. Functional scores for Short Form-12 mental component summary and Short Form-12 physical component summary were improved from 34.1 to 43.6 and 42.3 to 50.0, respectively. Twenty of 21 participants were opioid-free at 36 months.

Zuidema et al. [51] reported two cases of focal neuropathy of the lateral femoral cutaneous nerve (LFCN), and ilioinguinal nerve and genitofemoral nerve (IGN and GFN). After DRG-S implant, the participant with LFCN neuropathy reported 90% pain relief after 2 months. The participant with neuropathy at the IGN and GFN reported 100% pain relief at 3 months after DRG-S. Finally, Falowski et al. [48] reported one case of chronic intractable left L5 radiculopathy that was treated with DRG-S. The participant reported 100% pain relief at 6 weeks and had stopped taking baseline non-steroidal anti-inflammatory drugs.

A prospective pilot study by Koetsier et al. [55] evaluated DRG-S on nine patients with intractable large fiber polyneuropathy (Table 5). Etiologies included type II diabetes, chemotherapy-induced peripheral neuropathy (CIPN), chronic inflammatory demyelinating polyradiculoneuropathy, and idiopathic. In seven of the nine patients who underwent DRG-S implantation, daytime pain at 6 months decreased from 7.0 to 3.0, nighttime pain decreased from 5.4 to 1.0, and peak pain decreased from 9.0 to 4.0. The etiologies of polyneuropathy in this study were heterogeneous and there was no subgroup analysis between etiologies and outcome measures. However, the authors reported that the two patients with PDN had similar pain relief in comparison to other etiologies.

Grabnar et al. [56] reported DRG-S in a 50-year-old woman with a history of breast cancer and lower extremity CIPN. She had a successful 7-day DRG-S trial, achieving a decrease in VAS from 8 to 0, and her Douleur Neuropathique 4 (DN4) questionnaire score improved from 8/10 to 2/10. She has persistent pain relief 3 years later.

Overall, the body of literature for use of DRG-S in polyneuropathy is limited to case reports and prospective observational study data. There was very low-quality GRADE evidence supporting DRG-S use in reducing pain and impairment in polyneuropathy. According to the GRADE approach, the evidence quality for Koetsier et al. was initially considered as low, but ultimately was downgraded on the basis of indirectness with differing diagnoses of participants, notable methodological biases, imprecision from small sample sizes, and inclusion of case reports.

A systematic review concluded that there is moderate evidence for DRG-S in treatment of neuropathic pain of the trunk or lower extremities, although it does not specifically address pain confined to the groin [64]. Advantages of DRG-S over dorsal column SCS include targeting discrete areas, maintenance of efficacy with postural changes, and lack of paresthesia in non-targeted areas [6]. These unique features of DRGS posit it to be especially useful in post-herniorrhaphy groin pain, a notoriously challenging region to target via dorsal column SCS [65,66,67]. Inguinal hernia repair is a common procedure, and the literature suggests that between 5% and 25% of patients will manifest post-herniorrhaphy neuralgia [65, 68]. Thus, the frequency of hernia repair procedures along with the percentage of patients afflicted by post-herniorrhaphy neuralgia suggests a need for escalation of treatment options in patients not amenable to medical management only. In addition to post-herniorrhaphy groin pain, DRG-S may be a viable and effective treatment option for other painful etiologies affecting the groin such as CRPS, structural damage to the ilioinguinal, iliohypogastric, or genitofemoral nerves, post-vasectomy neuralgia, and chronic pelvic pain syndrome [66].

Schu et al. [9] conducted a multicenter, retrospective study of patients who underwent DRG-S for chronic intractable, neuropathic groin pain. Of the 29 patients who underwent DRG-S trial, 25 achieved 50% or greater pain reduction and underwent implantation. After a median follow-up of 26 weeks, 19 of 23 patients achieved greater than 50% reduction in pain intensity, with 11 of 19 patients reporting pain reduction greater than 80%. Similarly, another multicenter, retrospective study [68] reviewed 32 patients with chronic neuropathic groin pain and reported a mean reduction of 68.6% in NRS after DRG-S trial. Lead placement was performed at T12–L2 for most patients; however, the range of levels targeted included T9–S3. After analysis of varying lead arrays, the authors recommended that for post-herniorrhaphy patients, the optimal lead arrangement was either T12, L1, or L2 in combination with either L2 or L3 [68]. These findings are concordant with Morgalla et al. [10] reporting promising long-term results at 3-year follow-up in a prospective cohort study of 34 patients with chronic groin pain treated with DRG-S.

In summary, there is limited evidence pooled from both retrospective and prospective observational studies highlighting that DRG-S may be an effective treatment modality for chronic, intractable neuropathic groin pain with most patients obtaining relief when leads were placed at the T12–L2 level.

Total knee arthroplasty (TKA) is one of the most common surgeries with over 700,000 performed in the USA annually. Unfortunately, 8–34% of post-TKA patients experience a complicated postsurgical course with persistent neuropathic postsurgical pain (NPP) [66, 67]. DRG-S may offer a viable treatment modality for patients with persistent neuropathic knee pain refractory to conventional medical management.

Hunter et al. [68] conducted a multicenter, retrospective registry study of DRG-S for neuropathic knee pain. Their results of 23 patients showed 66.1% mean pain relief and 30% of patients reported greater than 80% improvement in pain intensity. Their analysis of a variety of lead combinations found that DRG-S provided a pain score reduction of 86.4% when targeting the L4 DRG and 74% reduction when targeting the L3 DRG. Thus, the study recommended targeting both the L3 and L4 DRG for treatment of neuropathic knee pain; if the implanting provider desires to only place one lead, the authors reported that preference should be given to L4 DRG placement given its slightly higher efficacy in pain reduction compared to L3 DRG placement [68].

Similarly, Martin et al. [69] conducted a secondary analysis of a prospective study of 14 patients with neuropathic knee pain. Of 14 patients, 12 had a successful trial and received a permanent implant, including five patients with postsurgical knee pain and seven patients with pain secondary to traumatic injury. At a mean follow-up of 34 months, they found an 80% median improvement in pain score and a 54% mean reduction in oral morphine equivalents. Lead placement was determined during DRG-S trial, with eight patients achieving a positive response to L3 DRG-S alone, one patient from L4 DRG-S alone, and three patients requiring combined L3 and L4 DRG-S to adequately cover their painful region.

In a prospective, crossover study comparing DRG-S and dorsal column SCS for CRPS confined to the knee, 10 of 12 (83%) patients preferred DRG-S while two of 12 (17%) patients chose to proceed with dorsal column SCS [33]. The lead placement for DRG-S was at both the L3 and L4 DRGs for all patients [33]. This crossover study concluded that in patients with chronic CRPS confined to the knee, DRG-S is an effective treatment and that DRG-S was preferred over dorsal column SCS in 83% of patients.

There are currently no RCTs analyzing DRG-S for knee pain, although the observational studies outlined above provide low-quality evidence supporting DRG-S of the L3 and L4 DRG as a treatment option for patients with refractory neuropathic pain confined to the knee.

Painful conditions of the foot commonly treated with DRG-S include CRPS and phantom limb pain. Sensory innervation for the foot is primarily from the L4, L5, and S1 nerve roots. Foot pain may be difficult to target with traditional dorsal column SCS compared to DRG-S [49]. It is postulated that there is convergence between DRGs at adjacent levels, so placing a lead at one level may result in paresthesias and pain relief at adjacent levels [28, 70]. As outlined above, the ACCURATE trial [6] and another prospective observational study by Liem et al. [5] highlight evidence for DRG-S in treating foot pain.

For chronic foot pain, the most common levels of DRG-S placement are at the L4, L5, and S1 DRGs. In one case of CRPS, recurrence developed after left-sided transtibial amputation and subsequent neuroma excision. Dorsal column SCS was attempted, although the patient did not experience adequate paraesthesia coverage of the stump [35]. DRG-S was subsequently attempted at the left L4 DRG with 75% coverage of stump pain. At 17-month follow-up, the patient reported 60% pain relief with DRG-S. In a case series by Skaribas et al. [28] five patients with CRPS of the foot and prior back surgery underwent S1 DRG-S. The single S1 DRG electrode resulted in pain relief of the entire foot and all five patients achieved substantial impr