High-quality evidence suggests the use of spinal cord stimulation (SCS) for the management of complex regional pain syndrome (CRPS) and chronic pain associated with spine and lower extremities.

For the management of chronic refractory painful disorders, neurostimulation is the well-established treatment method. The choice of optimal management option for an individual is always based on the characteristics of the disease, its location and origin of pain. However, debate for selecting the best neural targets and stimulation techniques continues among clinicians. New insights in the brain and spinal cord physiology with advancements in technology and programming help in evolving the clinical practice of neuromodulation. Simultaneously, recent prospective, well designed and high-quality evidence also supplements the fundamental research supporting neuromodulation.

Rationale behind research:

Peer-reviewed literature constitutes consensus statements and best practices for neurostimulation, but no systematic literature review has been conducted yet. There is a need to conduct systematic review synthesizing the latest evidence for SCS therapy, the neurostimulation mode with the longest clinical history.

Objective:

The present systematic review aims to report the foundational knowledge of care for chronic pain patients by investigating the quality of the evidence for SCS, presenting key points, and discussing findings from specific studies. These findings may help in enhancing patient safety, outcomes, and access when integrated into clinical practice.

Literature Search:

A comprehensive literature search was conducted using the electronic databases such as Embase, MEDLINE, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, CINAHL, and Scopus to generate a list of study abstracts for screening. The SCS literature search was made from January 1995 to October 2018 by using a combination of keywords such as "spinal cord stimulation," "dorsal column stimulation," "low-frequency stimulation," "tonic and conventional spinal cord stimulation," and "high-frequency spinal cord stimulation." Data sources, constituting relevant systematic reviews and cited articles were searched manually for possible additional studies. Duplicates were excluded.

Inclusion and exclusion criteria:

Inclusion criteria were limited to:

• RCT's of SCS that included patients suffering from chronic or intractable pain greater than one year
• SCS trials that included patients with CRPS, back pain or both back and limb pain
• Studies of SCS with a minimum patient follow up of 3 months

Exclusion criteria: The studies with retrospective design, a small number of patients and abstracts only were excluded from the analysis.

Study selection:

Abstracts and titles of eligible studies were screened by reviewers independently. Original studies in the literature list which were eligible for further review were identified. If a study was found to be relevant, the full-text manuscript was obtained and reviewed.

Quality Assessment and Risk of Bias:

The quality of studies was rated using the modified Interventional Pain Management Techniques-Quality Appraisal of Reliability and Risk of Bias Assessment. This was used in addition to the US Preventative Services Task Force (USPSTF) which was used to assign a final level of evidence. The assessment of the risk of bias was done using the Cochrane Collaboration's Risk of Bias tool. This tool assesses the risk of bias related to the method of randomization, allocation concealment and blinding of patients.

Data Extraction and Analysis:

Data related to patient demographics, study design, baseline characteristics, intervention and outcome measures were extracted by at least two reviewers independently. RCT's were scored using the SCS scoring system. Two additional reviewers without known bias were recruited if any discrepancies resulted in different overall scores of quality. This process was followed until an accurate reproducible scoring was provided by expert opinion.

Study Outcomes:

The primary outcome of the study was the improvement in pain after SCS therapy.

Outcomes:

Study characteristics: Among 6 included RCT's, five trials were identified as RCT's and one trial was identified as a prospective, comparative, nonrandomized pilot study

Study quality: All the studies were graded as high quality and level 1 evidence (strong) for SCS in treatment of low back pain, neuropathic pain and CRPS with low to moderate risk of bias

Effect of intervention on the outcome:

• A significant reduction in pain associated with axial back/lumbar radiculopathy or neuralgia and complex regional pain syndrome was observed in patients treated with SCS, as evidenced from high-quality RCT's

The findings of the current systematic review of the literature demonstrated SCS as safe and effective for the treatment of neuropathic pain failed back surgery syndrome (FBSS), and CRPS. These findings were consistent with the results of previous reviews and meta-analysis, and further, expand the scope of SCS in the management of back pain with or without radicular symptomatology.

Among the 6 included trials, five trials included back pain and neuralgia patients treated with SCS. The outcomes of many of these studies included comparisons of different waveforms or comparison of tonic stimulation with newer pulse trains and novel waveforms. Taken together, these five RCT's suggested various key points such as the efficacy of conventional SCS is higher in relieving pain than reoperation and conventional medical management alone for patients with FBSS. Conventional SCS was also found to be effective for chronic pain syndromes even in studies evaluating new technologies, waveforms, and frequencies. The new frequencies and waveforms may provide a greater likelihood of pain relief and increased response rate as compared to conventional stimulation, though some patients continue to prefer tonic stimulation.

Only one prospective, comparative, nonrandomized pilot study supports the use of SCS for CRPS among multiple observational studies. This study included patients with CRPS, either treated with physical therapy (PT) and SCS or PT alone. An improvement in pain relief, quality of life and functional measures was observed in patients treated with SCS and PT when compared to patients treated with PT alone. Patients treated with SCS also reported a greater range of motion and improvement in limb, when compared to patients treated with PT alone suggesting that SCs also facilitates objective measures of rehabilitation.

About general observations concerning adverse effects, either device-related adverse events (lead migration, implantable pulse generator issues), technique-related AEs (loss of stimulation effect), or biological adverse events (infection, seroma, pain at lead or battery site) were considered in most of the studies. However, no particular SCS technique resulted in an increase in AEs that needs further investigation.