Peripheral mononeuropathy is a focal form of neuropathic pain in which a single nerve is affected, typically following trauma or surgery. Despite the availability of pharmacological and non-pharmacological treatments, less than 50% of patients with neuropathic pain achieve satisfactory relief with first-line treatment, and approximately 15–30% of patients with common mononeuropathies develop persistent symptoms for which therapeutic options are limited. Spinal cord stimulation (SCS) has demonstrated sustained analgesic efficacy in painful diabetic polyneuropathy and complex regional pain syndrome, but prospective evidence in refractory peripheral mononeuropathic pain was previously lacking.

This thesis presents the SCIMONO pilot study (NCT06546371), a prospective single-center exploratory study at Erasmus Medical Centre evaluating the clinical effects of SCS in patients with refractory peripheral mononeuropathic pain. Complementary exploratory analyses characterize multivariate somatosensory profiles at baseline and assess longitudinal changes following SCS, alongside descriptive assessment of endogenous pain modulation before and after treatment. 12 adults with electromyography (EMG)-confirmed peripheral mononeuropathy refractory to at least six months of conventional medical management were enrolled. After a two-week trial phase, patients achieving ≥30% pain reduction
proceeded to permanent implantation. A three-month comparison phase evaluated four stimulation paradigms (tonic, fast, burst (delivered as microburst), and contour) in counterbalanced order, followed by a three-month preference phase.

The primary outcome was change in pain intensity (NRS) from baseline to six months. Secondary outcomes included health-related quality of life (EQ-5D), emotional functioning (HADS), and pain-related functional interference (BPI). Quantitative sensory testing (QST) and conditioned pain modulation (CPM) were assessed at baseline and six-month follow-up to characterize the multivariate somatosensory profile of the cohort and to explore whether these dimensions
change following SCS, thereby generating mechanistic hypotheses alongside the clinical outcome evaluation.

Of the 12 enrolled patients, 10 completed six-month follow-up and were included in the final analysis. One patient had not yet reached six-month follow-up at the time of analysis, and one patient withdrew during follow-up due to headache. Median NRS decreased significantly from 7.0 (IQR 6.1–7.4) at baseline to 3.8 (IQR 2.4–5.0) at six months, with a median within-patient reduction of −3.3 points (p = 0.01), exceeding the minimal clinically important difference of 2 points. Eight patients (80%) achieved ≥30%, of whom five achieved ≥50% pain reduction. EQ-5D and BPI scores improved significantly and exceeded their respective minimal clinically important differences. HADS scores did not change
significantly. Differences between the four stimulation paradigms were not statistically significant and paradigm preferences varied across patients. No serious adverse events occurred.

Exploratory somatosensory analysis of baseline QST scores in this cohort revealed heterogeneous sensory profiles, varying continuously along dimensions of sensory loss and mechanical sensitization. The single non-responder showed marked vibration detection loss at baseline, indicative of impaired large-fiber afferent integrity. This was accompanied by virtually no reduction in somatosensory asymmetry and a qualitatively distinct pattern of somatosensory change following SCS, generating the hypothesis that large-fiber afferent integrity may be a relevant determinant of SCS efficacy. At the group level among participants with complete six-month follow-up data (n=10), no individual QST parameter changed significantly after Holm correction. Baseline CPM was heterogeneous with no consistent association with treatment response. A preliminary increase in inhibitory PPT-based CPM responses at six-month follow-up compared to baseline suggests that SCS may engage descending inhibitory pathways in the central nervous system, though this observation remains hypothesis-generating.

These findings provide the first prospective evidence supporting the feasibility of SCS in refractory peripheral mononeuropathic pain and inform the design of a future sham-controlled randomized trial. The exploratory somatosensory analyses suggest that pre-implantation multivariate QST profiling may carry predictive value for SCS response beyond current selection criteria, warranting prospective investigation in adequately powered studies.