Dissecting central post-stroke pain: a controlled symptom-psychophysical characterization

Abstract

Central post-stroke pain affects up to 12% of stroke survivors and is notoriously refractory to treatment. However, stroke patients often suffer from other types of pain of non-neuropathic nature (musculoskeletal, inflammatory, complex regional) and no head-to-head comparison of their respective clinical and somatosensory profiles has been performed so far. We compared 39 patients with definite central neuropathic post-stroke pain with two matched control groups: 32 patients with exclusively non-neuropathic pain developed after stroke and 31 stroke patients not complaining of pain. Patients underwent deep phenotyping via a comprehensive assessment including clinical exam, questionnaires and quantitative sensory testing to dissect central post-stroke pain from chronic pain in general and stroke. While central post-stroke pain was mostly located in the face and limbs, non-neuropathic pain was predominantly axial and located in neck, shoulders and knees (P < 0.05). Neuropathic Pain Symptom Inventory clusters burning (82.1%, n = 32, P < 0.001), tingling (66.7%, n = 26, P < 0.001) and evoked by cold (64.1%, n = 25, P < 0.001) occurred more frequently in central post-stroke pain. Hyperpathia, thermal and mechanical allodynia also occurred more commonly in this group (P < 0.001), which also presented higher levels of deafferentation (P < 0.012) with more asymmetric cold and warm detection thresholds compared with controls. In particular, cold hypoesthesia (considered when the threshold of the affected side was <41% of the contralateral threshold) odds ratio (OR) was 12 (95% CI: 3.8-41.6) for neuropathic pain. Additionally, cold detection threshold/warm detection threshold ratio correlated with the presence of neuropathic pain (ρ = -0.4, P < 0.001). Correlations were found between specific neuropathic pain symptom clusters and quantitative sensory testing: paroxysmal pain with cold (ρ = -0.4; P = 0.008) and heat pain thresholds (ρ = 0.5; P = 0.003), burning pain with mechanical detection (ρ = -0.4; P = 0.015) and mechanical pain thresholds (ρ = -0.4, P < 0.013), evoked pain with mechanical pain threshold (ρ = -0.3; P = 0.047). Logistic regression showed that the combination of cold hypoesthesia on quantitative sensory testing, the Neuropathic Pain Symptom Inventory, and the allodynia intensity on bedside examination explained 77% of the occurrence of neuropathic pain. These findings provide insights into the clinical-psychophysics relationships in central post-stroke pain and may assist more precise distinction of neuropathic from non-neuropathic post-stroke pain in clinical practice and in future trials.

Keywords: central neuropathic pain; central post-stroke pain; neuropathic pain phenotyping; post-stroke pain; quantitative sensory testing.

Graphical Abstract

Figure 1

STROBE flow diagram of patient recruitment according to pain characteristics. CPSP, central post-stroke pain; PSP-Non, non-neuropathic post-stroke pain; No-Pain, stroke patients without chronic pain.

Figure 2

Pain area and cold hypoesthesia distribution according to pain groups frequency. (A) Pain area distribution according to pain groups.*P was <0.05 for all areas except pelvic and lumbar regions. (B) Cold hypoesthesia distribution. *P < 0.0167 (with Bonferroni correction for multiple comparisons). (C) PPT *P < 0.0167 (with Bonferroni correction for multiple comparison). Tested areas: 1, temporal and masseter; 2, trapezius; 3, rhomboid; 4, levator scapulae, supraspinatus; 5, wrist and finger extensors; 6, first dorsal interosseous; 7, quadratus lumborum; 8, gluteus maximus; 9, piriformis; 10, vastus lateralis; 11, gastrocnemius. CPSP, central post-stroke pain; PSP-Non, non-neuropathic post-stroke pain; No-Pain, stroke without pain.

Figure 3

QST assessment with sensory asymmetry evaluation and somatosensory gain and loss of function. (A) Asymmetry evaluation through the ratio of affected side per unaffected side. The QST ratio is represented as median and interquartile ranges in a log10 scale. Kruskal–Wallis followed by pairwise comparisons were performed using Mann–Whitney for two independent samples with a Bonferroni correction for multiple comparisons. Statistical significance was accepted at the P < 0.0167 level.*P < 0.05 for analyses between groups and P < 0.0167 for pairwise comparisons. (B) Percentage of patients with somatosensory gain of function. χ² test and Fisher test were performed followed by pairwise comparisons with Bonferroni correction for multiple comparisons. Statistical significance was accepted at the P < 0.0167. (C) Percentage of patients with somatosensory loss of function. *P < 0.05 for analyses between groups and P < 0.0167 for pairwise comparisons. CPSP, central Post-Stroke Pain; PSP-Non, non-neuropathic post-stroke pain; No-Pain, stroke without pain; CDT, cold detection threshold; WDT, warm detection threshold; MDT, mechanical detection threshold; CPT, cold pain threshold; HPT, heat pain threshold; MPT, mechanical pain threshold; VDT, vibration detection threshold; STCP, suprathreshold cold pain—pain referred according to the Numeric Pain Rating Scale (NRS) after suprathreshold cold pain stimulus; STHP, suprathreshold heat pain—NRS after suprathreshold heat pain stimulus; STMP, NRS after suprathreshold mechanical pain stimulus; WUR, wind up ratio.