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 to controls. In particular, cold hypoesthesia (considered when the threshold of the affected side was less than 41% of the contralateral threshold) odds ratio 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.

Site matters: Central neuropathic pain characteristics and somatosensory findings after brain and spinal cord lesions

“…This cross-sectional study, part of the Central Pain Initiative Project, focused on assessing and treating CNP [10,18,19]. Here we aimed to compare the pain characteristics and sensory profile of CNP secondary to stroke to CNP secondary to spinal cord lesions in NMO.…”

“…All participants were volunteers and provided written informed consent before inclusion. Some of the general clinical data of some included patients were reported in publications from this initiative [10,19]. All participants suffered an ischemic or hemorrhagic stroke confirmed by imaging (computed tomography or magnetic resonance imaging [MRI]) at least 3 months before the evaluation or had previous myelitis secondary to NMO diagnosed by a neuroinflammatory diseases specialist using the current diagnostic criteria [22].…”

“…It was classified into three categories: absent, low to moderate (m-AS scale score 1 or 2 in at least one limb), and moderate to severe (m-AS scale score >2 in at least one limb). Muscle strength was measured according to the Medical Research Council (MRC) Scale for Muscle Strength scoring system, which was grouped into four severity grades: grade 0 (MRC in all limbs = 5), grade 1 (MRC = 4 in at least one limb), grade 2 (MRC = 2 or 3 in at least one limb), and grade 3 (MRC = 0 or 1 in at least one limb) [10].…”

“…This approach is sound, but some limiting factors still need to be explored in guiding treatment [9]. One of them is that the large majority of studies describing patient profiles in neuropathic pain include exclusively, or essentially, peripheral neuropathic pain [10][11][12][13][14][15][16][17]. This is expected, because most patients with neuropathic pain have peripheral rather than central neuropathic pain (CNP).…”

“…However, it remains unknown whether the correlations and findings related to sensory findings from QST and sensory symptoms are the same in patients with CNP of different etiologies. Classical studies have reported symptom somatosensory profile correlations of patients with a single etiology of CNP [10][11][12][13][14][15][16][17]. For example, in patients with syringomyelia, higher severity of spinal cord injury (SCI) was associated with more intense deep pain and paresthesia/dysesthesia, whereas patients with evoked pain had more preserved spinothalamic and lemniscal pathways [15].…”