Dynamic Brain Imaging Response to Spinal Cord Stimulation Differential Frequencies DiFY SCS-PET Clinical Trial.

OBJECTIVES: This study with sequential 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)-computed tomography (CT) scanning was designed to investigate any objective measurable effect of differential frequency stimulation (40 Hz, 4000 Hz, and 10,000 Hz) on specific pain matrix areas in patients who underwent spinal cord stimulation (SCS) for intractable lumbar neuropathic pain. MATERIALS AND METHODS: In this single-center, randomized, blinded study, four brain 18F-FDG PET scans were performed for each patient-at baseline before SCS implant and after 40-Hz, 4000-Hz, and 10,000-Hz stimulation. After 40-Hz stimulation for four weeks, patients were randomized 1:1 (4000 Hz/10,000 Hz), crossing over at another four weeks. 18F-FDG PET-CT brain scans acquired on the GE-Discovery 710 PET system (GE Healthcare, Chicago, IL) with 128-slice CT (250-MBq dose) were analyzed using the PMOD software (PMOD Technologies Ltd, Zurich, Switzerland). A total of 18 pain regions, the right and left prefrontal cortex (PFC), insula, anterior cingulate cortex (ACC), hippocampus, amygdala, primary somatosensory cortices, secondary somatosensory cortices (SSCII), thalami, parabrachial, and periaqueductal gray (PAG), were analyzed. RESULTS: A total of 14 patients received 40 Hz for four weeks before crossing over to 10,000 Hz/4000 Hz. A total of 57 PET-CT scans (15 for baseline and 14 each for 40 Hz, 4000 Hz, and 10,000 Hz) were analyzed for maximum standardized uptake value (SUVmax), with a statistically significant difference in SUVmax between 40 Hz and baseline (p = 0.002) and 4000 Hz and baseline (p = 0.001) when pooled across 18 pain matrices. There was no statistical difference in SUVmax between 10,000 Hz and baseline. The pooled analysis showed a proportionately higher thalamic region reduction (59.5%) in metabolic activity than other pain matrices, PFC (52%), insula (50%), ACC (52%), SSCII (49%), and PAG (52%). CONCLUSION: This large cohort of brain PET scans (n = 57) shows statistically significant differences in brain metabolic activity at 40 Hz and 4000 Hz from baseline, with effect on both nociceptive and affect-cognitive pathways (proportionately higher reduction in the thalamus), highlighting the possible mechanism of SCS. CLINICAL TRIAL REGISTRATION: The Clinicaltrials.gov registration number for the study is NCT03716557.

Effectiveness of high dose spinal cord stimulation for non-surgical intractable lumbar radiculopathy - HIDENS Study.

OBJECTIVES: Spinal cord stimulation (SCS) is being increasingly used in non-surgical intractable low back pain. This study was designed to evaluate the efficacy of high-dose (HD) SCS utilizing sub-perception stimulation with higher frequency and pulse width in non-surgical predominant low-back pain population at 12 months. MATERIALS AND METHODS: A total of 20 patients were recruited (280 screened between March 2017 and July 2018) to undergo percutaneous fluoroscopic-guided SCS (Medtronic 8 contact standard leads and RestoreR IPG), with T8 and T9 midline anatomical parallel placement. Sixteen patients completed 12 months follow-up (500 Hz frequency, 500 µs pulse width, and 25% pulse density). Differences in patients' clinical outcome (NRS back, NRS leg, ODI, PGIC, and PSQ) and medication usage (MQS) at 1, 3, and 12 months from the baseline were assessed using non-parametric Wilcoxon paired test. RESULTS: The mean NRS scores for back pain (baseline 7.53) improved significantly at 1, 3, and 12 months; 2.78 (p < 0.001), 4.45 (p = 0.002), and 3.85 (p = 0.002), respectively. The mean NRS score for leg pain (baseline 6.09) improved significantly at 1 and 3 months; 1.86 (p < 0.001) and 3.13 (p = 0.010), respectively. Mean NRS for leg pain at 12 months was 3.85 (p = 0.057). ODI and sleep demonstrated significant improvement as there was consistent improvement in medication particularly opioid usage (MQS) at 12 months. CONCLUSIONS: This study demonstrates that anatomical placement of leads with sub-perception HD stimulation could provide effective pain relief in patients who are not candidates for spinal surgery.

The Effects of Radiofrequency Neurotomy Using a Strip-Lesioning Device on Patients with Sacroiliac Joint Pain: Results from a Single-Center, Randomized, Sham-Controlled Trial.

BACKGROUND: Radiofrequency neurotomy (RFN) is a therapy aimed at providing lasting back pain relief for sacroiliac joint (SIJ) pain. A recent advancement in RFN is a strip lesioning technique that involves placement of a single curved electrode and a 3-pole design that facilitates the creation of 5 overlapping lesions. These lesions form one long strip lesion accessible through a single entry point, without the need for multiple punctures. Although the early case series data looks promising, there is lack of long-term, randomized, controlled study evaluating the strip-lesioning system for SIJ pain. OBJECTIVES: The purpose of this study was to examine the safety and effectiveness of RFN using a strip lesioning device for reduction of SIJ pain. STUDY DESIGN: Prospective, double-blind, randomized, sham-controlled trial with 6-month follow-upSETTING: A tertiary care interventional pain management center in the UK METHODS: Patients with SIJ pain with positive diagnostic local anesthetic blocks were randomly assigned (2:1) to either the sham (no RF lesions performed) or the active group (RF lesions performed). The primary endpoint was improvement of pain using the Numeric Rating Scale (NRS-11) at 3 months. Results were analyzed using nonparametric tests. Safety, secondary, and long-term outcome data were also collected. RESULTS: Seventeen of 30 enrolled patients were randomly assigned to active treatment (n = 11) or sham treatment (n = 6). At 3 months, the mean NRS-11 score for the active group had decreased significantly, from 8.1 (± 0.8) at baseline to 3.4 (± 2.0) (P < 0.001). The sham group did not experience a statistically or clinically meaningful decrease in mean NRS-11 score from baseline (7.3 ± 0.8) to 3 months (7.0 ± 1.7). On average, patients in the active group moved from borderline anxiety at baseline (9.4 ± 5.9) to no anxiety (6.6 ± 6.3) at 3 months. Results were similar at 6 months. LIMITATIONS: Recruitment was stopped at 30 enrolled patients, only 17 of whom were randomly assigned to active or sham treatment, after the interim analysis indicated a statistically significant (P < 0.001) difference in the pain outcome between the treatment and the sham groups. CONCLUSIONS: This study demonstrated that radiofrequency neurotomy using a strip lesioning device is an appropriate therapy to treat SIJ pain. KEY WORDS: Radiofrequency, sacroiliac joint pain, low back pain, neurotomy, randomized controlled trial, simplicity.

A pilot study investigating whether quantitative sensory testing alters after treatment in patients with fibromyalgia.

BACKGROUND: Fibromyalgia is a chronic musculoskeletal pain condition that is often associated with sleep disturbances and fatigue. The pathophysiology of fibromyalgia is not understood, but indirect evidence suggests a central dysfunction of the nociceptive modulating system. The aim of this study was to evaluate whether quantitative sensory testing detects a change in pain thresholds in fibromyalgia patient receiving pregabalin treatment. METHODS: A total of 25 patients were recruited for the study and received routine pregabalin, but only 14 patients completed the treatment. Assessment of pressure pain thresholds and changes in conditioned pain modulation using ischaemic pain as a conditioning stimulus were measured at baseline and every 4 weeks for 12 weeks. Fibromyalgia impact questionnaire, PainDETECT and SF-12 were also completed. RESULTS: Patients with fibromyalgia demonstrated a less-efficient conditioned pain modulation at baseline. An efficient conditioned pain modulation was observed at 1 month and this was maintained until the final visit. Pressure pain thresholds (PPTs) showed a significant improvement from baseline. Patients also reported a similar magnitude of improvements in PainDETECT, fibromyalgia impact questionnaire (FIQ) and its impact on daily life and change in outcome for SF-12. CONCLUSION: This pilot study reports an increase in PPTs and improved conditioned pain modulation response after commencing pregabalin, which was maintained at 12 weeks, and this was supported by positive pain scores. Pregabalin is a licenced treatment for fibromyalgia in Europe, and its response to central sensitisation, particularly 'dynamic responses', has not been reported. We conclude that pregabalin has the potential to reduce peripheral and central sensitisation in patients with fibromyalgia, as measured using quantitative sensory testing.