Pain relief and functional improvement in patients with neuropathic pain associated with spinal cord injury: an exploratory analysis of pregabalin clinical trials

Abstract

Background: Characterizing relationships between pain relief and function can inform patient management decisions. This analysis explored graphically the relationship between pain relief and functional improvement in patients with neuropathic pain associated with spinal cord injury in two clinical trials of pregabalin.

Methods: This was a post hoc analysis of two randomized, double-blind, clinical trials in patients who were treated with pregabalin (n=181) or placebo (n=172) for neuropathic pain associated with spinal cord injury. The bivariate relationship between percent pain relief and absolute change in the functional outcomes with placebo and pregabalin was evaluated graphically using scatter plots, and loess curves illustrated the extent of the relationship between pain and function. Linear trend analysis evaluated the statistical significance of these relationships using Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT)-based thresholds of pain reduction (<15%, 15% <30%, 30% to <50%, and ≥50%). Outcome measures included modified Brief Pain Inventory pain interference with function in one of the studies and the Medical Outcomes Study Sleep Scale (an 11-point Numeric Rating Scale) and the Hospital Anxiety and Depression Scale (HADS) for the pooled studies.

Results: Data ellipses showed a shift with pregabalin relative to placebo toward greater improvement with increasing pain relief for all outcome measures except HADS. Loess curves suggested a relationship between increased pain relief and improved function except for HADS, with the clearest relationship observed for sleep. Linear trend analysis showed significant relationships between pain and Medical Outcomes Study Sleep Scale (P<0.0001) and between pain and function on the modified Brief Pain Inventory Interference Index and most individual items (P<0.05).

Conclusion: Greater functional improvements were generally achieved at higher levels of clinically significant pain reduction. Pregabalin resulted in shifts from placebo toward greater functional improvement with greater pain relief.

Keywords: function; neuropathic pain; pregabalin; sleep; spinal cord injury.

Figure 1

Scatter plots of the relationship between pain reduction and pain interference with function assessed by the ten-item MBPI Total Interference score (A and B) and the Affective (C and D) and Activity (E and F) subscales derived from the seven-item BPI. Notes: Data are for patients in Cardenas et al. Panels on the left show bivariate data ellipses at 50% and 95% confidence regions for the observed spread and strength of the relationship between pain and function. Panels on the right are loess curves exploring the extent of the relationship. Broken vertical lines indicate clinically relevant pain improvement thresholds of 15%, 30%, and 50%. Abbreviations: MBPI, modified Brief Pain Inventory; SCI, spinal cord injury.

Figure 2

Scatter plots of the relationship between pain reduction and sleep assessed using the MOS-SS (A and B) and the patient daily diary using an 11-point sleep interference Numeric Rating Scale (C and D). Notes: Data are for patients from the two studies., Panels on the left show data ellipses at 50% and 95% confidence regions for the observed spread and strength of the relationship between pain and function. Panels on the right are loess curves exploring the extent of the relationship. Broken vertical lines indicate clinically relevant pain improvement thresholds of 15%, 30%, and 50%. Abbreviations: MOS-SS, Medical Outcomes Study Sleep Scale; SCI, spinal cord injury.

Figure 3

Scatter plots of the relationship of pain reduction with changes in anxiety (A and B) and depression (C and D) measured using the HADS. Notes: Data are for patients from the two studies., Panels on the left show bivariate data ellipses at 50% and 95% confidence regions for the observed spread and strength of the relationship between pain and function. Panels on the right are loess curves exploring the extent of the relationship. Broken vertical lines indicate clinically relevant pain improvement thresholds of 15%, 30%, and 50%. Abbreviations: HADS, Hospital Anxiety and Depression Scale; SCI, spinal cord injury.