Data from a substudy of SUNBURST suggest that burst stimulation of the spinal cord regulates the medial pain pathway to a greater extent than tonic stimulation, through selective modulation of the dorsal anterior cingulate cortex. Writing in Neuromodulation, Thomas Yearwood and colleagues postulate “an inherent difference in the central neural mechanisms during burst and tonic stimulation, which could potentially alter the patient’s perception of pain”.
Burst spinal cord stimulation (SCS) delivers groups of pulses at a higher frequency and at amplitudes much lower than tonic stimulation. The authors hypothesised that a comparison of the central neural activation patterns during tonic and burst stimulation has the potential to investigate differences in neural processing and the underlying mechanisms involved in modulating the perception of pain.
Because there is not an SCS burst system that is compatible with functional magnetic resonance imaging (fMRI), the authors use fluorodeoxyglucose positron emission tomography (FDG-PET) to evaluate differences in neural activity during tonic and burst stimulation, and assess any corresponding correlation with patient reported pain scores. FDG-PET uses an analogue of glucose as the biologically active molecule.
The SUNBURST trial was a prospective multicentre randomised open-label crossover study; this sub-study collected seven patients in one study site as an extra visit during SUNBURST, adding the FGD-PET and the pain vigilance and awareness questionnaire (PVAQ). Participants were randomised 1:1 to receive either tonic or burst stimulation for 12 weeks; at the end of this time they crossed over to the other treatment. A PET scan was taken at baseline and after 12 weeks of tonic stimulation and after 12 weeks of burst stimulation.
Among the inclusion criteria were age ≥22 years, and presence of chronic intractable pain of the trunk and/or limbs, with an average score of ≥60 on the visual analogue score (VAS) seven-day pain diary. Outcome parameters for the efficiency of treatment were measured with the VAS and the PVAQ, which assessed the overall impact of pain intensity and the emotional component related to pain, and were conducted at baseline, prior to implantation, and at the end (after 12 weeks) of each of the two study arms of tonic or burst stimulation.
Compared to baseline, the VAS score for pain reduced by an average of 41.5% (standard deviation [SD] 34.3) among those receiving tonic stimulation, and by 36.2% (SD 21.8) among those receiving burst stimulation. A suppression of 14.4% (SD 34.3%) was observed for tonic stimulation compared to burst stimulation. On the PVAQ scale, tonic stimulation demonstrated an increase of 9.3% versus a reduction of 17.8% for burst stimulation, when compared against baseline. Direct comparison of tonic and burst stimulation showed a reduction of 26.3% (SD 21.7) for burst stimulation.
Imaging data showed a significant increase in metabolic rate in the premotor cortex from baseline with both tonic and burst activity stimulation. There was also a significant increase in metabolic rate compared to baseline in the dorsal anterior cingulate cortex during burst stimulation.
A regression analysis for the VAS for pain and the metabolic changes between burst and tonic stimulation demonstrated a significant effect. A VAS for pain reduction was shown to correspond to an increased metabolic rate in the dorsal anterior cingulate cortex, the precuneus and the dorsal lateral prefrontal cortex. According to the researchers: “This suggests that the higher the pain suppression with burst stimulation, the larger the increase will be in the metabolic rate of the dorsal anterior cingulate cortex, the precuneus and the dorsal lateral prefrontal cortex in comparison to tonic stimulation.”
A small number of patients were included in this sub-study, with only one round of data acquisition. Despite this, say Yearwood et al, the findings “seem to confirm the previous electrophysiological findings that support burst stimulation having a larger impact on the medial pain pathway than tonic stimulation, as demonstrated by its selective modulation of the dorsal anterior cingulate cortex”.
The researchers call for larger studies, and add: “Studies using fMRI with an MRI compatible SCS burst device could further help to explain the underlying mechanism.”