Capsaicin 8% patch treatment for amputation stump and phantom limb pain: a clinical and functional MRI study

Abstract

Purpose: The aim of this study was to measure the efficacy of a single 60 min application of capsaicin 8% patch in reducing chronic amputation stump and phantom limb pain, associated hypersensitivity with quantitative sensory testing, and changes in brain cortical maps using functional MRI (fMRI) scans.

Methods: A capsaicin 8% patch (Qutenza) treatment study was conducted on 14 patients with single limb amputation, who reported pain intensity on the Numerical Pain Rating Scale ≥4/10 for chronic stump or phantom limb pain. Pain assessments, quantitative sensory testing, and fMRI (for the lip pursing task) were performed at baseline and 4 weeks after application of capsaicin 8% patch to the amputation stump. The shift into the hand representation area of the cerebral cortex with the lip pursing task has been correlated with phantom limb pain intensity in previous studies, and was the fMRI clinical model for cortical plasticity used in this study.

Results: The mean reduction in spontaneous amputation stump pain, phantom limb pain, and evoked stump pain were -1.007 (p=0.028), -1.414 (p=0.018), and -2.029 (p=0.007), respectively. The areas of brush allodynia and pinprick hypersensitivity in the amputation stump showed marked decreases: -165 cm², -80% (p=0.001) and -132 cm², -72% (p=0.001), respectively. fMRI analyses provided objective evidence of the restoration of the brain map, that is, reversal of the shift into the hand representation of the cerebral cortex with the lip pursing task (p<0.05).

Conclusion: The results show that capsaicin 8% patch treatment leads to significant reduction in chronic pain and, particularly, in the area of stump hypersensitivity, which may enable patients to wear prostheses, thereby improving mobility and rehabilitation. Phantom limb pain ("central" pain) and associated brain plasticity may be modulated by peripheral inputs, as they can be ameliorated by the peripherally restricted effect of the capsaicin 8% patch.

Keywords: amputation; capsaicin; fMRI; phantom limb pain.

Figure 1

Study design flow diagram. Abbreviations: fMRI, functional magnetic resonance imaging; PGIC, Patient Global Impression of Change; QST, quantitative sensory testing.

Figure 2

Capsaicin 8% patch application. Note: The capsaicin 8% patch (A) and patch application to the affected stump area (B).

Figure 3

Pain scores at baseline and after capsaicin 8% patch treatment. Notes: Difference in pain scores over time from baseline for spontaneous stump pain (A), phantom limb pain (B), and evoked stump pain (C) in patients treated with capsaicin 8% patch. * Significant; ** very significant, *** highly significant.

Figure 4

Short Form (SF) McGill pain score at baseline and end of study. Notes: SF-McGill pain scores for continuous (A), intermittent (B), neuropathic (C), and affective (D) descriptors of pain in patients treated with capsaicin 8% patch, at baseline and after patch application. ** Very significant, *** highly significant.

Figure 5

Amputation stump hypersensitivity in a patient before (A) and after (B) capsaicin 8% patch treatment. Notes: Areas of mechanical dynamic allodynia (distal to green line), static allodynia (distal to red line), and pinprick hypersensitivity (distal to blue line) were found to be markedly decreased after treatment.

Figure 6

Areas of allodynia and hyperalgesia at baseline and end of study. Notes: Areas of mechanical dynamic allodynia (A) and pinprick hypersensitivity (B) in patients at baseline and after capsaicin 8% patch application. ** Very significant, *** highly significant.

Figure 7

Effect of lip pursing > rest averaged across both First and Second scans and across all patients (whole-brain analysis using FSL with fixed effects, cluster corrected for multiple comparisons p<0.05). Abbreviation: FSL, FMRIB Software Library.

Figure 8

Difference between scans (First > Second scan) of lip pursing > rest averaged across completed patients, showing a decrease (reversal) of the shift into the hand representation of the cerebral cortex with the lip pursing task (in green, arrowed). Images flipped so that left is contralateral to the amputation and right is ipsilateral (FSL with fixed effects, cluster corrected for multiple comparisons p<0.05). Abbreviation: FSL, FMRIB Software Library.