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.

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.

Clinical trials and tribulations: lessons from spinal cord injury studies registered on ClinicalTrials.gov.

STUDY DESIGN: Article. OBJECTIVE: ClinicalTrials.gov is an online trial registry that provides public access to information on past, present, and future clinical trials. While increasing transparency in research, the quality of the information provided in trial registrations is highly variable. The objective of this study is to assess key areas of information on ClinicalTrials.gov in interventional trials involving people with spinal cord injuries. SETTING: Interventional trials on ClinicalTrials.gov involving people with spinal cord injuries. METHODS: A subset of data on interventional spinal cord injury trials was downloaded from ClinicalTrials.gov. Reviewers extracted information pertaining to study type, injury etiology, spinal cord injury characteristics, timing, study status, and results. RESULTS: Of the interventional trial registrations reviewed, 62.5%, 58.6%, and 24.3% reported injury level, severity, and etiology, respectively. The timing of intervention relative to injury was reported in 72.8% of registrations. Most trials identified a valid study status (89.2%), but only 23.5% of those completed studies had posted results. CONCLUSIONS: Our review provides a snapshot of interventional clinical trials conducted in the field of spinal cord injury and registered in ClinicalTrials.gov. Areas for improvement were identified with regards to reporting injury characteristics, as well as posting results.

Pain-autonomic interaction: A surrogate marker of central sensitization.

BACKGROUND: Central sensitization represents a key pathophysiological mechanism underlying the development of neuropathic pain, often manifested clinically as mechanical allodynia and hyperalgesia. Adopting a mechanism-based treatment approach relies highly on the ability to assess the presence of central sensitization. The aim of the study was to investigate potential pain-autonomic readouts to operationalize experimentally induced central sensitization in the area of secondary hyperalgesia. METHODS: Pinprick evoked potentials (PEPs) and sympathetic skin responses (SSRs) were recorded in 20 healthy individuals. Three blocks of PEP and SSR recordings were performed before and after heat-induced secondary hyperalgesia. All measurements were also performed before and after a control condition. Multivariate analyses were performed using linear mixed-effect regression models to examine the effect of experimentally induced central sensitization on PEP and SSR parameters (i.e. amplitudes, latencies and habituation) and on pinprick pain ratings. RESULTS: The noxious heat stimulation induced robust mechanical hyperalgesia with a significant increase in PEP and SSR amplitudes (p < 0.001) in the area of secondary hyperalgesia. Furthermore, PEP and SSR habituation were reduced (p < 0.001) after experimentally induced central sensitization. CONCLUSIONS: The findings demonstrate that combined recordings of PEPs and SSRs are sensitive to objectify experimentally induced central sensitization and may have a great potential to reveal its presence in clinical pain conditions. Corroborating current pain phenotyping with pain-autonomic markers has the potential to unravel central sensitization along the nociceptive neuraxis and might provide a framework for mechanistically founded therapies. SIGNIFICANCE: Our findings provide evidence that combined recordings of sympathetic skin responses (SSRs) and pinprick evoked potentials (PEPs) might be able to unmask central sensitization induced through a well-established experimental pain model in healthy individuals. As such, these novel readouts of central sensitization might attain new insights towards complementing clinical pain phenotyping.

New life for an old idea: Assessing tonic heat pain by means of participant controlled temperature.

BACKGROUND: Temporal changes of pain perception to prolonged tonic heat pain are conventionally assessed using a computerized visual analog scale. Such a rating-based approach is, however, prone to floor and ceiling effects, which limit the assessment of temporal changes in perception. Thus, alternative methods that overcome these shortcomings are warranted. NEW METHOD: The aim of this study was to assess the feasibility and reliability of a psychophysical approach, i.e., participant-controlled temperature (PCT), to evaluate ongoing human perception of tonic heat pain. Fifty participants were presented with a 45 °C stimulus on the non-dominant hand, and were instructed to maintain their initial sensation for two minutes via a feedback controller in the dominant hand. A subset of participants (n = 17) performed PCT tonic heat protocols on two different days to determine the test-retest reliability. As participants controlled temperature to maintain a stable pain perception, any adjustments made reflected shifts in their perception of heat. RESULTS: In 33 (71.7%) participants, we observed an initial adaptation (participant increased temperature) followed by temporal summation of pain (participant decreased temperature). Twelve participants (26.1%) showed only adaptation and one (2.2%) only temporal summation. No sex differences were observed, nor did the initial rating of pain have an effect on PCT outcomes. Temporal summation of pain showed moderate to substantial reliability upon retest. CONCLUSIONS: PCT represents can be reliably performed using a contact heat stimulator to measure the temporal summation of pain. The standardized setup and overall good reliability of the outcome measures facilitate a sound implementation into the clinical work-up of patients with pain conditions.