Neuromodulation: Overview

Abstract
Objectives: Cancer pain is among the most prevalent and challenging symptoms in cancer care, with up to 95% of patients with late-stage cancer experiencing moderate-to-severe pain. Conventional pharmacologic treatments, including opioids, carry risks, and patients' conditions may be refractory to medical management or have contraindications. Neurostimulation techniques, such as spinal cord stimulation (SCS), dorsal root ganglion stimulation (DRGS), and peripheral nerve stimulation (PNS), have shown promise in treating treatment-induced cancer pain. However, a comprehensive review focusing on these techniques for cancer-induced pain alone is necessary.

Materials and methods: A comprehensive literature review was conducted using Medline, Embase, and Cochrane Library data bases, focusing on studies from 2000 onward. Inclusion criteria included interventional and observational studies reporting on SCS, DRGS, and PNS in cancer-induced pain. Studies addressing treatment-induced pain, systematic reviews, meta-analyses, and non-English studies were excluded. Data were extracted and evaluated using the Grades of Recommendation, Assessment, Development, and Evaluation system.

Results: The search yielded 831 references, with 24 studies meeting the inclusion criteria. Sixteen studies focused on SCS, seven on PNS, and two cases on DRGS. SCS showed significant pain reduction, with an average decrease in numeric rating scale (NRS) scores from 8.0 to 2.2 over an average 8.4-month follow-up period. PNS also indicated substantial pain relief, with NRS scores decreasing from 8.29 to 3.04 over an average 5.2-month follow-up period. DRGS, although less studied, showed a reduction in NRS scores from 6.0 to 1.0 over an average 6.0-month follow-up period. SCS was associated with a significant reduction in opioid use, with average reported morphine equivalent daily dose (MEDD) change from 1152.2 mg to 739.7 mg over an average 5.0-month period, whereas PNS and DRGS had limited impact on opioid consumption, with no reported MEDD change.

Conclusions: Our scoping review synthesizes evidence on neurostimulation interventions for treating cancer-induced pain. Current evidence suggests that interventions such as SCS, DRGS, and PNS may provide clinically meaningful pain relief in patients with cancer-induced pain. Several studies also reported improvements in functionality and quality of life. However, the level of evidence is limited owing to the lack of prospective comparative studies, clinical and methodologic heterogeneity, and small sample sizes.

Abstract
Objectives: This systematic review compares the long-term efficacy of cylindrical-lead spinal cord stimulation (CL-SCS) vs paddle-lead spinal cord stimulation (Paddle-SCS) for chronic pain management.

Materials and methods: We included prospective and retrospective studies with at least ten patients reporting on the efficacy of either lead type. Primary outcomes were pain score reduction (measured by the visual analog scale [VAS] and numeric rating scale [NRS]) and 50% pain relief after at least 12 months. Secondary outcomes included functional disability and complications, such as lead migration and infection rates. Meta-analyses compared effect sizes, while meta-regression and subgroup analyses addressed heterogeneity.

Results: A total of 96 studies, comprising 7726 patients, met the inclusion criteria. Paddle-SCS demonstrated superior pain reduction, with a standardized mean difference (SMD) of 5.37 (95% CI [5.35, 5.38]) compared with CL-SCS, which had an SMD of 4.09 (95% CI [4.08, 4.10]) on the VAS. However, CL-SCS outperformed Paddle-SCS on the NRS, with SMDs of 4.39 vs 2.35, respectively. For 50% pain relief, Paddle-SCS had a success rate of 41.4%, as opposed to 35.4% for CL-SCS. Paddle-SCS showed a lower migration rate (4.3% vs 7.2% for CL-SCS) but higher infection rates (5.0% vs 3.3%).

Conclusions: Paddle-SCS offers superior pain reduction (as measured by the VAS) and a lower migration rate, but a higher infection risk compared with CL-SCS. CL-SCS showed better outcomes as measured by the NRS. The choice between Paddle-SCS and CL-SCS should be individualized according to patient-specific factors and treatment goals. Further research with rigorous study designs is needed to provide clearer comparisons between these interventions.

Abstract
Background: This study assessed the effect of expectation of analgesia on conditioned pain modulation (CPM) in healthy participants stratified into inhibitors and non-inhibitors.

Methods: A parallel CPM protocol was assessed on 21 women and 22 men across two sessions: baseline and expectation of analgesia, which was induced by a standardized audiovisual suggestion. The CPM assessment involved two different test stimuli (TS): mechanically controlled palpation and the pressure pain threshold, applied to two different regions: anterior temporalis and thenar eminence of the hand. The conditioning stimulus (CS) involved immersing the non-dominant forearm in cold water. The order of the TS and regions was randomized for each participant. The CPM protocol was performed three times, with a 1-min interval between TS/region sequences. After a 20-min rest, the CPM assessment was repeated (two blocks in total). The standard error of measurement (SEM) was computed to identify inhibitors (inhibitory responses) and non-inhibitors (including non-inhibitors and facilitatory responses). Cochran's Q, ANOVA and ANCOVA were applied to the data (p < 0.05).

Results: There was a significant decrease in the proportion of non-inhibitors during the expectation of analgesia session (32.6%-44.2%) when compared with the baseline session (51.2%-72.1%). The non-inhibitors exhibited a lower inhibitory CPM magnitude than the inhibitors only in block 1 of the baseline session. The expectation of analgesia resulted in an increased magnitude of the inhibitory CPM solely in non-inhibitors.

Conclusion: Expectation of analgesia can increase the inhibitory response of the CPM beyond the measurement error in healthy participants with a baseline non-inhibitory profile.

Significance: Several studies have investigated whether cognitive modulation can alter the magnitude of the inhibitory response of conditioned pain modulation (CPM), yet some gaps remain. This study accounted for measurement error to accurately determine changes in CPM influenced by expectation of analgesia.