Jan Rosner

Background: Neurophysiological assessments might advance the understanding of nonspecific chronic low back pain (nsCLBP) by quantifying altered pain processing and associated autonomic responses. Contact heat‐evoked potentials (CHEPs) and sympathetic skin responses (SSRs) were compared between nsCLBP patients and healthy controls (HCs), and their relationships with experimental and clinical pain ratings were explored. Methods: A total of 56 nsCLBP patients and 40 age‐ and sex‐matched HCs were included in this study. All participants underwent simultaneous recordings of CHEPs and SSRs in response to two blocks of 15 heat stimuli applied at the back (i.e., the patients’ clinical pain area) and the hand (nonpainful control area). Participants rated the perceived pain intensity of each contact heat stimulus using a numerical rating scale (0–10). The change of pain ratings, CHEP, and SSR amplitudes between blocks was calculated as habituation index. Results: SSR latencies were prolonged in patients compared to HCs ( F = 9.5, p = 0.003) and were shorter after back stimulation compared to hand stimulation ( F = 9.6, p < 0.001). No other group differences were observed. Clinical pain intensities in patients correlated (1) with contact heat pain ratings in both areas (back: rho = 0.27, p = 0.041, control area: rho = 0.272, p = 0.042) and (2) inversely with CHEP P2 latencies after hand stimulation (current pain: rho = −0.324, p = 0.019; average 4 weeks: rho = −0.320, p = 0.022). Conclusion: Prolonged SSR latencies in nsCLBP might indicate a dysregulated pain–autonomic response. Trial Registration: Clinicaltrials.gov_identifier: NCT04433299

Introduction: In 85% of patients with chronic low back pain (CLBP), no specific pathoanatomical cause can be identified. Besides primary peripheral drivers within the lower back, spinal or supraspinal sensitization processes might contribute to the patients' pain. Objectives: The present study conceptualized the most painful area (MP) of patients with nonspecific CLBP as primarily affected area and assessed signs of peripheral, spinal, and supraspinal sensitization using quantitative sensory testing (QST) in MP, a pain-free area adjacent to MP (AD), and a remote, pain-free control area (CON). Methods: Fifty-nine patients with CLBP (51 years, SD = 16.6, 22 female patients) and 35 pain-free control participants individually matched for age, sex, and testing areas (49 years, SD = 17.5, 19 female participants) underwent a full QST protocol in MP and a reduced QST protocol assessing sensory gain in AD and CON. Quantitative sensory testing measures, except paradoxical heat sensations and dynamic mechanical allodynia (DMA), were Z-transformed to the matched control participants and tested for significance using Z-tests (α = 0.001). Paradoxical heat sensations and DMA occurrence were compared between cohorts using Fisher's exact tests (α = 0.05). The same analyses were performed with a high-pain and a low-pain CLBP subsample (50% quantile). Results: Patients showed cold and vibration hypoesthesia in MP (all Ps < 0.001) and mechanical hyperalgesia (P < 0.001) and more frequent DMA (P = 0.044) in AD. The results were mainly driven by the high-pain CLBP subsample. In CON, no sensory alterations were observed. Conclusion: Mechanical hyperalgesia and DMA adjacent to but not within MP, the supposedly primarily affected area, might reflect secondary hyperalgesia originating from spinal sensitization in patients with CLBP.

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.

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 (ICC_2,1), 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.

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.

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 one month to elicit comments before final approval by ASIA and ISCoS. Results: The ISCIPBDS (Version 3.0) was updated in order 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.

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.

Objective: To explore the so-called “structure-function paradox” in individuals with focal spinal lesions by means of tract-specific MRI coupled with multi-modal evoked potentials and quantitative sensory testing. Methods: Individuals with signs and symptoms attributable to cervical myelopathy (i.e., no evidence of competing neurological diagnosis) were recruited in the Balgrist University Hospital, Zurich, Switzerland between February 2018 and March 2019. We evaluated the relationship between the extent of structural damage within spinal nociceptive pathways (i.e., dorsal horn, spinothalamic tract, anterior commissure) assessed with atlas-based MRI , and 1) the functional integrity of spinal nociceptive pathways measured with contact heat-, cold-, and pinprick- evoked potentials and 2) clinical somatosensory phenotypes assessed with quantitative sensory testing. Results: Sixteen individuals (mean age 61 years) with either degenerative (N=13) or post-traumatic (N=3) cervical myelopathy participated in the study. Most individuals presented with mild myelopathy (modified Japanese Orthopaedic Association score (mJOA)>15; N=13). 71% of individuals presented with structural damage within spinal nociceptive pathways on MRI. Yet, 50% of these individuals presented with complete functional sparing (i.e., normal contact heat-, cold-, and pinprick- evoked potentials). The extent of structural damage within spinal nociceptive pathways was neither associated with functional integrity of thermal (heat: p=0.57; cold: p=0.49) and mechano-nociceptive pathways (p=0.83) nor with the clinical somatosensory phenotype (heat: p=0.16; cold: p=0.37; mechanical: p=0.73). The amount of structural damage to the spinothalamic tract did not correlate with spinothalamic conduction velocity (p>0.05; rho=-0.11). Conclusions: Our findings provide neurophysiological evidence to substantiate that structural damage in the spinal cord does not equate to functional somatosensory deficits. This study recognizes the pronounced structure-function paradox in cervical myelopathies and underlines the inevitable need for a multi-modal phenotyping approach to reveal the eloquence of lesions within somatosensory pathways.

Objective To track the interplay between (micro-) structural changes along the trajectories of nociceptive pathways and its relation to the presence and intensity of neuropathic pain (NP) after spinal cord injury (SCI). Methods A quantitative neuroimaging approach employing a multiparametric mapping protocol was used, providing indirect measures of myelination (via contrasts such as magnetisation transfer (MT) saturation, longitudinal relaxation (R1)) and iron content (via effective transverse relaxation rate (R2*)) was used to track microstructural changes within nociceptive pathways. In order to characterise concurrent changes along the entire neuroaxis, a combined brain and spinal cord template embedded in the statistical parametric mapping framework was used. Multivariate source-based morphometry was performed to identify naturally grouped patterns of structural variation between individuals with and without NP after SCI. Results In individuals with NP, lower R1 and MT values are evident in the primary motor cortex and dorsolateral prefrontal cortex, while increases in R2* are evident in the cervical cord, periaqueductal grey (PAG), thalamus and anterior cingulate cortex when compared with pain-free individuals. Lower R1 values in the PAG and greater R2* values in the cervical cord are associated with NP intensity. Conclusions The degree of microstructural changes across ascending and descending nociceptive pathways is critically implicated in the maintenance of NP. Tracking maladaptive plasticity unravels the intimate relationships between neurodegenerative and compensatory processes in NP states and may facilitate patient monitoring during therapeutic trials related to pain and neuroregeneration.