Dissecting Central Post-stroke Pain: a Controlled Symptom-psychophysical Characterization

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 ( < 0.05). Neuropathic Pain Symptom Inventory clusters burning (82.1%,  = 32,  < 0.001), tingling (66.7%,  = 26,  < 0.001) and evoked by cold (64.1%,  = 25,  < 0.001) occurred more frequently in central post-stroke pain. Hyperpathia, thermal and mechanical allodynia also occurred more commonly in this group ( < 0.001), which also presented higher levels of deafferentation ( < 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 ( = -0.4,  < 0.001). Correlations were found between specific neuropathic pain symptom clusters and quantitative sensory testing: paroxysmal pain with cold ( = -0.4;  = 0.008) and heat pain thresholds ( = 0.5;  = 0.003), burning pain with mechanical detection ( = -0.4;  = 0.015) and mechanical pain thresholds ( = -0.4,  < 0.013), evoked pain with mechanical pain threshold ( = -0.3;  = 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.