Contact-Heat Evoked Potentials: Insights into Pain Processing in CRPS Type I.

Purpose: The pathophysiological mechanisms underlying the development of chronic pain in complex regional pain syndrome (CRPS) are diverse and involve both peripheral and central changes in pain processing, such as sensitization of the nociceptive system. The aim of this study was to objectively distinguish the specific changes occurring at both peripheral and central levels in nociceptive processing in individuals with chronic CRPS type I. Patients and Methods: Nineteen individuals with chronic CRPS type I and 16 age- and sex-matched healthy controls (HC) were recruited. All individuals underwent a clinical examination and pain assessment in the most painful limb, the contralateral limb, and a pain-free control area to distinguish between peripheral and central mechanisms. Contact-heat evoked potentials (CHEPs) were recorded after heat stimulation of the three different areas and amplitudes and latencies were analyzed. Additionally, quantitative sensory testing (QST) was performed in all three areas. Results: Compared to HC, CHEP amplitudes in CRPS were only increased after stimulation of the painful area (p=0.025), while no increases were observed for the pain-free control area (p=0.14). None of the CHEP latencies were different between the two cohorts (all p>0.23). Furthermore, individuals with CRPS showed higher pain ratings after stimulation of the painful limb compared to their contralateral limb (p=0.013). Lastly, compared to HC, mechanical (p=0.012) and thermal (p=0.046) sensitivity was higher in the painful area of the CRPS cohort. Conclusion: This study provides neurophysiological evidence supporting an intact thermo-nociceptive pathway with signs of peripheral sensitization, such as hyperexcitable primary afferent nociceptors, in individuals with CRPS type I. This is further supported by the observation of mechanical and thermal gain of sensation only in the painful limb. Additionally, the increased CHEP amplitudes might be related to fear-induced alterations of nociceptive processing.

The effect of experimentally induced gluteal muscle weakness on joint kinematics, reaction forces, and dynamic balance performance during deep bilateral squats.

Squatting is a common daily activity and fundamental exercise in resistance training and closed kinetic chain programs. The aim of this study was to investigate the effects of an experimentally induced weakness of the gluteal muscles on joint kinematics, reactions forces (JRFs), and dynamic balance performance during deep bilateral squats in healthy young adults. Ten healthy adults received sequential blocks of (1) branch of the superior gluteal nerve to the tensor fasciae latae (SGNtfl) muscle, (2) superior gluteal nerve (SGN), and (3) inferior gluteal nerve (IGN) on the dominant right leg. At the control condition and following each block, the participants were instructed to perform deep bilateral squats standing on two force plates. Hip, knee, ankle, and pelvis kinematics did not differ significantly following iatrogenic weakness of gluteal muscles. The most important finding was the significant differences in JRFs following SGN and IGN block, with the affected hip, patellofemoral, and ankle joint demonstrating lower JRFs, whereas the contralateral joints demonstrated significantly higher JRFs, especially the patellofemoral joint which demonstrated an average maximum difference of 1.43 x body weight compared with the control condition. When performing a deep bilateral leg squat under SGN and IGN block, the subjects demonstrated an increased center of pressure (CoP) range and standard deviation (SD) in mediolateral compared with the control condition. These results imply that squat performance changes significantly following weakness of gluteal muscles and should be considered when assessing and training athletes or patients with these injuries.

Central neuropathic pain.

Central neuropathic pain arises from a lesion or disease of the central somatosensory nervous system such as brain injury, spinal cord injury, stroke, multiple sclerosis or related neuroinflammatory conditions. The incidence of central neuropathic pain differs based on its underlying cause. Individuals with spinal cord injury are at the highest risk; however, central post-stroke pain is the most prevalent form of central neuropathic pain worldwide. The mechanisms that underlie central neuropathic pain are not fully understood, but the pathophysiology likely involves intricate interactions and maladaptive plasticity within spinal circuits and brain circuits associated with nociception and antinociception coupled with neuronal hyperexcitability. Modulation of neuronal activity, neuron-glia and neuro-immune interactions and targeting pain-related alterations in brain connectivity, represent potential therapeutic approaches. Current evidence-based pharmacological treatments include antidepressants and gabapentinoids as first-line options. Non-pharmacological pain management options include self-management strategies, exercise and neuromodulation. A comprehensive pain history and clinical examination form the foundation of central neuropathic pain classification, identification of potential risk factors and stratification of patients for clinical trials. Advanced neurophysiological and neuroimaging techniques hold promise to improve the understanding of mechanisms that underlie central neuropathic pain and as predictive biomarkers of treatment outcome.

Sensory phenotypes in complex regional pain syndrome and chronic low back pain-indication of common underlying pathomechanisms.

Introduction: First-line pain treatment is unsatisfactory in more than 50% of chronic pain patients, likely because of the heterogeneity of mechanisms underlying pain chronification. Objectives: This cross-sectional study aimed to better understand pathomechanisms across different chronic pain cohorts, regardless of their diagnoses, by identifying distinct sensory phenotypes through a cluster analysis. Methods: We recruited 81 chronic pain patients and 63 age-matched and sex-matched healthy controls (HC). Two distinct chronic pain cohorts were recruited, ie, complex regional pain syndrome (N = 20) and low back pain (N = 61). Quantitative sensory testing (QST) was performed in the most painful body area to investigate somatosensory changes related to clinical pain. Furthermore, QST was conducted in a pain-free area to identify remote sensory alterations, indicating more widespread changes in somatosensory processing. Results: Two clusters were identified based on the QST measures in the painful area, which did not represent the 2 distinct pain diagnoses but contained patients from both cohorts. Cluster 1 showed increased pain sensitivities in the painful and control area, indicating central sensitization as a potential pathomechanism. Cluster 2 showed a similar sensory profile as HC in both tested areas. Hence, either QST was not sensitive enough and more objective measures are needed to detect sensitization within the nociceptive neuraxis or cluster 2 may not have pain primarily because of sensitization, but other factors such as psychosocial ones are involved. Conclusion: These findings support the notion of shared pathomechanisms irrespective of the pain diagnosis. Conversely, different mechanisms might contribute to the pain of patients with the same diagnosis.

Increased cranio-caudal spinal cord oscillations are the cardinal pathophysiological change in degenerative cervical myelopathy.

Introduction: Degenerative cervical myelopathy (DCM) is the most common cause of non-traumatic incomplete spinal cord injury, but its pathophysiology is poorly understood. As spinal cord compression observed in standard MRI often fails to explain a patient's status, new diagnostic techniques to assess DCM are one of the research priorities. Minor cardiac-related cranio-caudal oscillations of the cervical spinal cord are observed by phase-contrast MRI (PC-MRI) in healthy controls (HCs), while they become pathologically increased in patients suffering from degenerative cervical myelopathy. Whether transversal oscillations (i.e., anterior-posterior and right-left) also change in DCM patients is not known. Methods: We assessed spinal cord motion simultaneously in all three spatial directions (i.e., cranio-caudal, anterior-posterior, and right-left) using sagittal PC-MRI and compared physiological oscillations in 18 HCs to pathological changes in 72 DCM patients with spinal canal stenosis. The parameter of interest was the amplitude of the velocity signal (i.e., maximum positive to maximum negative peak) during the cardiac cycle. Results: Most patients suffered from mild DCM (mJOA score 16 (14-18) points), and the majority (68.1%) presented with multisegmental stenosis. The spinal canal was considerably constricted in DCM patients in all segments compared to HCs. Under physiological conditions in HCs, the cervical spinal cord oscillates in the cranio-caudal and anterior-posterior directions, while right-left motion was marginal [e.g., segment C5 amplitudes: cranio-caudal: 0.40 (0.27-0.48) cm/s; anterior-posterior: 0.18 (0.16-0.29) cm/s; right-left: 0.10 (0.08-0.13) cm/s]. Compared to HCs, DCM patients presented with considerably increased cranio-caudal oscillations due to the cardinal pathophysiologic change in non-stenotic [e.g., segment C5 amplitudes: 0.79 (0.49-1.32) cm/s] and stenotic segments [.g., segment C5 amplitudes: 0.99 (0.69-1.42) cm/s]). In contrast, right-left [e.g., segment C5 amplitudes: non-stenotic segment: 0.20 (0.13-0.32) cm/s; stenotic segment: 0.11 (0.09-0.18) cm/s] and anterior-posterior oscillations [e.g., segment C5 amplitudes: non-stenotic segment: 0.26 (0.15-0.45) cm/s; stenotic segment: 0.11 (0.09-0.18) cm/s] remained on low magnitudes comparable to HCs. Conclusion: Increased cranio-caudal oscillations of the cervical cord are the cardinal pathophysiologic change and can be quantified using PC-MRI in DCM patients. This study addresses spinal cord oscillations as a relevant biomarker reflecting dynamic mechanical cord stress in DCM patients, potentially contributing to a loss of function.

Intra- and inter-session reliability of electrical detection and pain thresholds of cutaneous and muscle primary afferents in the lower back of healthy individuals.

To advance evidence-based practice and targeted treatments of low back pain (LBP), a better pathophysiological understanding and reliable outcome measures are required. The processing of nociceptive information from deeper somatic structures (e.g., muscle, fascia) might play an essential role in the pathophysiology of LBP. In this study, we measured the intra- and inter-session reliability of electrical detection and pain thresholds of cutaneous and muscle primary afferents of the lower back. Twenty healthy participants attended two study visits separated by 27.7 ± 1.7 days. To determine the location-specific electrical detection threshold (EDT) and pain threshold (EPT), needle electrodes were inserted in the epidermal layer over, and in the lumbar erector spinae muscle. Additionally, established quantitative sensory testing (QST) parameters were assessed. Reliability was determined by differences between measurements, intraclass correlation coefficients (ICC2,1), Bland-Altman plots, and standard error of measurement (SEM). Correspondence between QST parameters and electrical thresholds was assessed using Pearson's correlation. Except for cutaneous EPT, no significant (p ≤ 0.05) intra- and inter-session differences were observed. Excellent intra-session reliability was shown for cutaneous and intramuscular electrical stimulations and all QST parameters (ICC: 0.76-0.93). Inter-session reliabilities were good (ICC: 0.74-0.75) except for electrical stimulations (ICC: 0.08-0.36). Limits of agreement and SEM were higher for inter-session than intra-session. A medium to strong relationship was found between electrical and mechanical/pressure pain thresholds. In conclusion, cutaneous and intramuscular electrical stimulation will potentially close an important diagnostic gap regarding the selective examination of deep tissue afferents and provide location-specific information for the excitability of non-nociceptive and nociceptive afferents.

The international spinal cord injury pain basic data set (version 3.0).

STUDY DESIGN: Expert opinion, feedback, revisions, and final consensus. OBJECTIVES: To update the International Spinal Cord Injury Pain Basic Data Set (ISCIPBDS version 2.0) and incorporate suggestions from the SCI pain clinical and research community with respect to overall utility. SETTING: International. METHODS: The ISCIPBDS working group evaluated these suggestions and made modifications. The revised ISCIPBDS (Version 3.0) was then reviewed by members of the International SCI Data Sets Committee, the American Spinal Injury Association (ASIA) Board, the International Spinal Cord Society (ISCoS) Executive and Scientific Committees, individual reviewers and societies, and posted on the ASIA and ISCoS websites for 1 month to elicit comments before final approval by ASIA and ISCoS. RESULTS: The ISCIPBDS (Version 3.0) was updated to make the dataset more flexible and useful: 1. The assessment can be based on the patient's perception of several of his/her "worst" pain(s) or based on the International SCI Pain (ISCIP) Classification-defined or other pain types, depending on the specific research questions or clinical needs. 2. Pain interference should usually be rated for overall pain but may also be used for specific pain problems if needed. 3. An optional pain drawing was added to complement the check box documentation of pain location. 4. Data categories consistent with the Extended Pain Dataset list of current treatments were added. 5. Several new training cases were added.

Priming of the autonomic nervous system after an experimental human pain model.

Modulated autonomic responses to noxious stimulation have been reported in experimental and clinical pain. These effects are likely mediated by nociceptive sensitization, but may also, more simply reflect increased stimulus-associated arousal. To disentangle between sensitization- and arousal-mediated effects on autonomic responses to noxious input, we recorded sympathetic skin responses (SSRs) in response to 10 pinprick and heat stimuli before (PRE) and after (POST) an experimental heat pain model to induce secondary hyperalgesia (EXP) and a control model (CTRL) in 20 healthy females. Pinprick and heat stimuli were individually adapted for pain perception (4/10) across all assessments. Heart rate, heart rate variability, and skin conductance level (SCL) were assessed before, during, and after the experimental heat pain model. Both pinprick- and heat-induced SSRs habituated from PRE to POST in CTRL, but not EXP (P = 0.033). Background SCL (during stimuli application) was heightened in EXP compared with CTRL condition during pinprick and heat stimuli (P = 0.009). Our findings indicate that enhanced SSRs after an experimental pain model are neither fully related to subjective pain, as SSRs dissociated from perceptual responses, nor to nociceptive sensitization, as SSRs were enhanced for both modalities. Our findings can, however, be explained by priming of the autonomic nervous system during the experimental pain model, which makes the autonomic nervous system more susceptible to noxious input. Taken together, autonomic readouts have the potential to objectively assess not only nociceptive sensitization but also priming of the autonomic nervous system, which may be involved in the generation of distinct clinical pain phenotypes.NEW & NOTEWORTHY The facilitation of pain-induced sympathetic skin responses observed after experimentally induced central sensitization is unspecific to the stimulation modality and thereby unlikely solely driven by nociceptive sensitization. In addition, these enhanced pain-induced autonomic responses are also not related to higher stimulus-associated arousal, but rather a general priming of the autonomic nervous system. Hence, autonomic readouts may be able to detect generalized hyperexcitability in chronic pain, beyond the nociceptive system, which may contribute to clinical pain phenotypes.

Intrinsic brain connectivity alterations despite intact pain inhibition in subjects with neuropathic pain after spinal cord injury: a pilot study.

Endogenous pain modulation in humans is frequently investigated with conditioned pain modulation (CPM). Deficient pain inhibition is a proposed mechanism that contributes to neuropathic pain (NP) after spinal cord injury (SCI). Recent studies have combined CPM testing and neuroimaging to reveal neural correlates of CPM efficiency in chronic pain. This study investigated differences in CPM efficiency in relation to resting-state functional connectivity (rsFC) between 12 SCI-NP subjects and 13 age- and sex-matched healthy controls (HC). Twelve and 11 SCI-NP subjects were included in psychophysical and rsFC analyses, respectively. All HC were included in the final analyses. Psychophysical readouts were analysed to determine CPM efficiency within and between cohorts. Group differences of rsFC, in relation to CPM efficiency, were explored with seed-to-voxel rsFC analyses with pain modulatory regions, e.g. ventrolateral periaqueductal gray (vlPAG) and amygdala. Overall, pain inhibition was not deficient in SCI-NP subjects and was greater in those with more intense NP. Greater pain inhibition was associated with weaker rsFC between the vlPAG and amygdala with the visual and frontal cortex, respectively, in SCI-NP subjects but with stronger rsFC in HC. Taken together, SCI-NP subjects present with intact pain inhibition, but can be differentiated from HC by an inverse relationship between CPM efficiency and intrinsic connectivity of supraspinal regions. Future studies with larger cohorts are necessary to consolidate the findings in this study.

Directional recordings of somatosensory evoked potentials from the sensory thalamus in chronic poststroke pain patients.

OBJECTIVE: The aim of this feasibility study was to investigate the properties of median nerve somatosensory evoked potential (SEPs) recorded from segmented Deep Brain Stimulation (DBS) leads in the sensory thalamus (VP) and how they relate to clinical and anatomical findings. METHODS: We analyzed four patients with central post-stroke pain and DBS electrodes placed in the VP. Median nerve SEPs were recorded with referential and bipolar montages. Electrode positions were correlated with thalamus anatomy and tractography-based medial lemniscus. Early postoperative clinical paresthesia mapping was performed by an independent pain nurse. Finally, we performed frequency and time-frequency analyses of the signals. RESULTS: We observed differences of SEP amplitudes recorded along different directions in the VP. SEP amplitudes did not clearly correlate to both atlas-based anatomical position and fiber-tracking results of the medial lemniscus. However, the contacts of highest SEP amplitude correlated with the contacts of lowest effect-threshold to induce paraesthesia. CONCLUSIONS: SEP recordings from directional DBS leads offer additional information about the neurophysiological (re)organization of the sensory thalamus. SIGNIFICANCE: Directional recordings of thalamic SEPs bear the potential to assist clinical decision-making in DBS for pain.

Central sensitization in CRPS patients with widespread pain: a cross-sectional study.

OBJECTIVE: Widespread pain hypersensitivity and enhanced temporal summation of pain (TSP) are commonly reported in patients with complex regional pain syndrome (CRPS) and discussed as proxies for central sensitization. This study aimed to directly relate such signs of neuronal hyperexcitability to the pain phenotype of CRPS patients. METHODS: Twenty-one CRPS patients and 20 healthy controls (HC) were recruited. The pain phenotype including spatial pain extent (assessed in % body surface) and intensity were assessed and related to widespread pain hypersensitivity, TSP, and psychological factors. Quantitative sensory testing (QST) was performed in the affected, the contralateral and a remote (control) area. RESULTS: CRPS patients showed decreased pressure pain thresholds in all tested areas (affected: t(34) = 4.98, P < .001, contralateral: t(35) = 3.19, P = .005, control: t(31) = 2.65, P = .012). Additionally, patients showed increased TSP in the affected area (F(3,111) = 4.57, P = .009) compared to HC. TSP was even more enhanced in patients with a high compared to a low spatial pain extent (F(3,51) = 5.67, P = .008), suggesting pronounced spinal sensitization in patients with extended pain patterns. Furthermore, the spatial pain extent positively correlated with the Bath Body Perception Disturbance Scale (ρ = 0.491; P = .048). CONCLUSIONS: Overall, we provide evidence that the pain phenotype in CRPS, that is, spatial pain extent, might be related to sensitization mechanism within the central nociceptive system. This study points towards central neuronal excitability as a potential therapeutic target in patients with more widespread CRPS.

Deep Brain Stimulation of the Central Lateral and Ventral Posterior Thalamus for Central Poststroke Pain Syndrome: Preliminary Experience.

OBJECTIVE: The beneficial effects of thalamic deep brain stimulation (DBS) at various target sites in treating chronic central neuropathic pain (CPSP) remain unclear. This study aimed to evaluate the effectiveness of DBS at a previously untested target site in the central lateral (CL) thalamus, together with classical sensory thalamic stimulation (ventral posterior [VP] complex). MATERIALS AND METHODS: We performed a monocentric retrospective study of a consecutive series of six patients with CPSP who underwent combined DBS lead implantation of the CL and VP. Patient-reported outcome measures were recorded before and after surgery using the numeric rating scale (NRS), short-form McGill pain questionnaire (sf-MPQ), EuroQol 5-D quality-of-life questionnaire, and Beck Depression Inventory. DBS leads were reconstructed and projected onto a three-dimensional stereotactic atlas. RESULTS: NRS-but not sf-MPQ-rated pain intensity-was significantly reduced throughout the follow-up period of 12 months compared with baseline (p = 0.005, and p = 0.06 respectively, Friedman test). At the last available follow-up (12 to 30 months), three patients described a more than 50% reduction. Two of the three long-term responders were stimulated in the CL (1000 Hz, 90 µs, 3.5-5.0 mA), whereas the third preferred VP complex stimulation (50 Hz, 200 µs, 0.7-1.2 mA). No persistent procedure- or stimulation-associated side effects were noted. CONCLUSIONS: These preliminary findings suggest that DBS of the CL might constitute a promising alternative target in cases in which classical VP complex stimulation does not yield satisfactory postoperative pain reduction. The results need to be confirmed in larger, prospective series of patients.

Pain-autonomic measures reveal nociceptive sensitization in complex regional pain syndrome.

BACKGROUND: Allodynia and hyperalgesia are common signs in individuals with complex regional pain syndrome (CRPS), mainly attributed to sensitization of the nociceptive system. Appropriate diagnostic tools for the objective assessment of such hypersensitivities are still lacking, which are essential for the development of mechanism-based treatment strategies. OBJECTIVES: This study investigated the use of pain-autonomic readouts to objectively detect sensitization processes in CRPS. METHODS: Twenty individuals with chronic CRPS were recruited for the study alongside 16 age- and sex-matched healthy controls (HC). All individuals underwent quantitative sensory testing and neurophysiological assessments. Sympathetic skin responses (SSRs) were recorded in response to 15 pinprick and 15 noxious heat stimuli of the affected (CRPS hand/foot) and a control area (contralateral shoulder/hand). RESULTS: Individuals with CRPS showed increased mechanical pain sensitivity and increased SSR amplitudes compared with HC in response to pinprick and heat stimulation of the affected (p < 0.001), but not in the control area (p > 0.05). Habituation of pinprick-induced SSRs was reduced in CRPS compared to HC in both the affected (p = 0.018) and slightly in the control area (p = 0.048). Habituation of heat-induced SSR was reduced in CRPS in the affected (p = 0.008), but not the control area (p = 0.053). CONCLUSIONS: This is the first study demonstrating clinical evidence that pain-related autonomic responses may represent objective tools to quantify sensitization processes along the nociceptive neuraxis in CRPS (e.g. widespread hyperexcitability). Pain-autonomic readouts could help scrutinize mechanisms underlying the development and maintenance of chronic pain in CRPS and provide valuable metrics to detect mechanism-based treatment responses in clinical trials. SIGNIFICANCE: This study provides clinical evidence that autonomic measures to noxious stimuli can objectively detect sensitization processes along the nociceptive neuraxis in complex regional pain syndrome (CRPS) (e.g. widespread hyperexcitability). Pain-autonomic readouts may represent valuable tools to explore pathophysiological mechanisms in a variety of pain patients and offer novel avenues to help guide mechanism-based therapeutic strategies.

Supraspinal facilitation to repetitive painful stimulation: a laser-evoked potential study.

To better characterize central modulation mechanisms involved in the processing of daily repetitive painful stimulation, laser-evoked potentials (LEPs) were recorded at and away from the conditioning area in healthy participants. In addition, we aimed to evaluate a repetitive painful stimulation paradigm that could be conducted in a shorter time frame than previous studies. Collectively, continuous pain rating, warm and heat pain threshold results suggest that sensitivity to pain was reduced 24 h after the shortened repeated painful stimulation. Laser-evoked potentials revealed a significant increase in the contralateral arm to where the conditioning stimulus was applied. This finding was specific to noxious conditioning (i.e., not seen in the control brush experiment). These results provide neurophysiological evidence of pain facilitation resulting from prolonged exposure to painful heat, potentially arising in supraspinal structures.NEW & NOTEWORTHY We provide evidence for supraspinal faciliation measured via laser-evoked potentails in response to a shortened and methodologically improved repetitive painful stimulation paradigm, serving the broader scientific community, insofar as providing a paradigm can feasibly be completed in a caldendar week. These findings provide new evidence using laser-evoked potentials indicating increased activation of the anterior cingulate cortex during prolonged pain processing.

Indicators of central sensitization in chronic neuropathic pain after spinal cord injury.

BACKGROUND: Central sensitization is considered a key mechanism underlying neuropathic pain (NP) after spinal cord injury (SCI). METHODS: Two novel proxies for central sensitization were investigated in thoracic SCI subjects with (SCI-NP) and without NP (SCI-nonNP) compared to healthy controls (HC). Specifically, temporal summation of pain (TSP) was investigated by examining pain ratings during a 2-min tonic heat application to the volar forearm. Additionally, palmar heat-induced sympathetic skin responses (SSR) were recorded in order to reveal changes in pain-autonomic interaction above the lesion level. Pain extent was assessed as the percentage of the body area and the number of body regions being affected by NP. RESULTS: Enhanced TSP was observed in SCI-NP (+66%) compared to SCI-nonNP (-75%, p = 0.009) and HC (-59%, p = 0.021). In contrast, no group differences were found (p = 0.685) for SSR habituation. However, pain extent in SCI-NP was positively correlated with deficient SSR habituation (body area: r = 0.561, p = 0.024; body regions: r = 0.564, p = 0.023). CONCLUSIONS: These results support the value of TSP and heat-induced SSRs as proxies for central sensitization in widespread neuropathic pain syndromes after SCI. Measures of pain-autonomic interaction emerged as a promising tool for the objective investigation of sensitized neuronal states in chronic pain conditions. SIGNIFICANCE: We present two surrogate readouts for central sensitization in neuropathic pain following SCI. On the one hand, temporal summation of tonic heat pain is enhanced in subjects with neuropathic pain. On the other hand, pain-autonomic interaction reveals potential advanced measures in chronic pain, as subjects with a high extent of neuropathic pain showed diminished habituation of pain-induced sympathetic measures. A possible implication for clinical practice is constituted by an improved assessment of neuronal hyperexcitability potentially enabling mechanism-based treatment.

Anti- and Pro-Nociceptive mechanisms in neuropathic pain after human spinal cord injury.

BACKGROUND: Deficient endogenous pain modulation and increased nociceptive excitability are key features of central sensitization and can be assessed in humans by conditioned pain modulation (CPM, anti-nociceptive) and temporal summation of pain (TSP, pro-nociceptive), respectively. This study aimed to investigate these measures as proxies for central sensitization in subjects with chronic neuropathic pain (NP) after spinal cord injury (SCI). METHODS: In paraplegic subjects with NP (SCI-NP; n = 17) and healthy controls (HC; n = 17), parallel and sequential sham-controlled CPM paradigms were performed using pressure pain threshold at the hand, that is, above lesion level, as test stimulus. The conditioning stimulus was a noxious cold (verum) or lukewarm water bath (sham) applied contralaterally. Regarding pro-nociceptive mechanisms, a TSP protocol with individually-adjusted pressure pain stimuli at the thenar eminence was used. CPM and TSP magnitudes were related to intensity and spatial extent of spontaneous NP. RESULTS: Neither the parallel nor sequential sham-controlled CPM paradigm showed any significant inhibition of above-level pressure pain thresholds for SCI-NP or HC. Accordingly, no group difference in CPM capacity was found, however, subjects with more intense spontaneous NP showed lower inhibitory CPM capacity. TSP was observed for both groups but was not enhanced in SCI-NP. CONCLUSIONS: Our results do not support altered above-level anti- or pro-nociceptive mechanisms in SCI-NP compared with HC; however, they also highlight the relevance of spontaneous NP intensity with regards to the capacity of endogenous pain modulation in SCI subjects. SIGNIFICANCE: Central sensitization encompasses deficient endogenous pain modulation and increased nociceptive excitability. These two mechanisms can be assessed in humans by conditioned pain modulation and temporal summation of pain, respectively. Our data demonstrates a lack of descending pain inhibition only in subjects with severe neuropathic pain which may hint towards central sensitization at spinal and/or supra-spinal levels. Disentangling the mechanisms of endogenous pain modulation and neuronal hyperexcitability might improve mechanism-based treatment of neuropathic pain in subjects with spinal cord injury.

Comparison of axial and sagittal spinal cord motion measurements in degenerative cervical myelopathy.

BACKGROUND AND PURPOSE: The timing of decision-making for a surgical intervention in patients with mild degenerative cervical myelopathy (DCM) is challenging. Spinal cord motion phase contrast MRI (PC-MRI) measurements can reveal the extent of dynamic mechanical strain on the spinal cord to potentially identify high-risk patients. This study aims to determine the comparability of axial and sagittal PC-MRI measurements of spinal cord motion with the prospect of improving the clinical workup. METHODS: Sixty-four DCM patients underwent a PC-MRI scan assessing spinal cord motion. The agreement of axial and sagittal measurements was determined by means of intraclass correlation coefficients (ICCs) and Bland-Altman analyses. RESULTS: The comparability of axial and sagittal PC-MRI measurements was good to excellent at all cervical levels (ICCs motion amplitude: .810-.940; p < .001). Significant differences between axial and sagittal amplitude values could be found at segments C3 and C4, while its magnitude was low (C3: 0.07 ± 0.19 cm/second; C4: -0.12 ± 0.30 cm/second). Bland-Altman analysis showed a good agreement between axial and sagittal PC-MRI scans (coefficients of repeatability: minimum -0.23 cm/second at C2; maximum -0.58 cm/second at C4). Subgroup analysis regarding anatomic conditions (stenotic vs. nonstenotic segments) and different velocity encoding (2 vs. 3 cm/second) showed comparable results. CONCLUSIONS: This study demonstrates good comparability between axial and sagittal spinal cord motion measurements in DCM patients. To this end, axial and sagittal PC-MRI are both accurate and sensitive in detecting pathologic cord motion. Therefore, such measures could identify high-risk patients and improve clinical decision-making (ie, timing of decompression).

Cognitive Status Predicts Return to Functional Independence After Minor Stroke: A Decision Tree Analysis.

About two-thirds of patients with minor strokes are discharged home. However, these patients may have difficulties returning to their usual living activities. To investigate the factors associated with successful home discharge, our aim was to provide a decision tree (based on clinical data) that could identify if a patient discharged home could return to pre-stroke activities and to perform an external validation of this decision tree on an independent cohort. Two cohorts of patients with minor strokes gathered from stroke registries at the Hôpital Pitié-Salpêtrière and University Hospital Bern were included in this study (n = 105 for the construction cohort coming from France; n = 100 for the second cohort coming from Switzerland). The decision tree was built using the classification and regression tree (CART) analysis on the construction cohort. It was then applied to the validation cohort. Accuracy, sensitivity, specificity, false positive, and false-negative rates were reported for both cohorts. In the construction cohort, 60 patients (57%) returned to their usual, pre-stroke level of independence. The CART analysis produced a decision tree with the Montreal Cognitive Assessment (MoCA) as the first decision point, followed by discharge NIHSS score or age, and then by the occupational status. The overall prediction accuracy to the favorable outcome was 80% in the construction cohort and reached 72% accuracy in the validation cohort. This decision tree highlighted the role of cognitive function as a crucial factor for patients to return to their usual activities after a minor stroke. The algorithm may help clinicians to tailor planning of patients' discharge.

Cold evoked potentials elicited by rapid cooling of the skin in young and elderly healthy individuals.

Cold-evoked potentials (CEPs) constitute a novel electrophysiological tool to assess cold-specific alterations in somatosensory function. As an important step towards the clinical implementation of CEPs as a diagnostic tool, we evaluated the feasibility and reliability of CEPs in response to rapid cooling of the skin (-300 °C/s) and different stimulation sites in young and elderly healthy individuals. Time-locked electroencephalographic responses were recorded from at vertex in fifteen young (20-40 years) and sixteen elderly (50-70 years), individuals in response to 15 rapid cold stimuli (-300 °C/s) applied to the skin of the hand dorsum, palm, and foot dorsum. High CEP proportions were shown for young individuals at all sites (hand dorsum/palm: 100% and foot: 79%) and elderly individuals after stimulation of the hand dorsum (81%) and palm (63%), but not the foot (44%). Depending on the age group and stimulation site, test-retest reliability was "poor" to "substantial" for N2P2 amplitudes and N2 latencies. Rapid cooling of the skin enables the recording of reliable CEPs in young individuals. In elderly individuals, CEP recordings were only robust after stimulation of the hand, but particularly challenging after stimulation of the foot. Further improvements in stimulation paradigms are warranted to introduce CEPs for clinical diagnostics.