QST revealed more similarities than differences between CRPS-I, CRPS-II, and PNI: sensory loss occurred in 63% of CRPS-I and sensory gain in 81% of PNI patients.
This study determined patterns of ...sensory signs in complex regional pain syndrome (CRPS) type I and II and peripheral nerve injury (PNI). Patients with upper-limb CRPS-I (n=298), CRPS-II (n=46), and PNI (n=72) were examined with quantitative sensory testing according to the protocol of the German Research Network on Neuropathic Pain. The majority of patients (66%–69%) exhibited a combination of sensory loss and gain. Patients with CRPS-I had more sensory gain (heat and pressure pain) and less sensory loss than patients with PNI (thermal and mechanical detection, hypoalgesia to heat or pinprick). CRPS-II patients shared features of CRPS-I and PNI. CRPS-I and CRPS-II had almost identical somatosensory profiles, with the exception of a stronger loss of mechanical detection in CRPS-II. In CRPS-I and -II, cold hyperalgesia/allodynia (28%–31%) and dynamic mechanical allodynia (24%–28%) were less frequent than heat or pressure hyperalgesia (36%–44%, 67%–73%), and mechanical hypoesthesia (31%–55%) was more frequent than thermal hypoesthesia (30%–44%). About 82% of PNI patients had at least one type of sensory gain. QST demonstrates more sensory loss in CRPS-I than hitherto considered, suggesting either minimal nerve injury or central inhibition. Sensory profiles suggest that CRPS-I and CRPS-II may represent one disease continuum. However, in contrast to recent suggestions, small fiber deficits were less frequent than large fiber deficits. Sensory gain is highly prevalent in PNI, indicating a better similarity of animal models to human patients than previously thought. These sensory profiles should help prioritize approaches for translation between animal and human research.
The immune system is believed to be important in the initiation and maintenance of chronic pain.
The aim was to investigate whether patients with chronic painful polyneuropathy (PP) differ in ...cytokine profiles of serum and/or cerebrospinal fluid (CSF) compared with pain-free controls.
Thirty-nine patients (16 women and 23 men, mean age, 69.2 ± 12.7 years, range 41-92 years) with PP (mean duration 43 ± 48.3 months) were phenotyped with quantitative sensory testing and electroneurography, and serum and CSF samples were analyzed by 40-multiplexed, bead-based cytokine immunoassays. Results were compared with 36 age- and gender-matched patients with normal pressure hydrocephalus and absence of abnormal CSF findings.
Compared with controls, patients with PP had lower concentrations of several proinflammatory and anti-inflammatory chemokines and cytokines in CSF, and others showed the same tendency, among these were tumor necrosis factor-α (14.1 ± 10.0 vs 23.9 ± 16.4 pg/mL,
< 0.005), interleukin (IL)-2 (0.6 ± 0.4 vs 1.2 ± 0.6 pg/mL,
< 0.0001), IL-6 (4.7 ± 6.8 vs 7.3 ± 9 pg/mL,
= 0.001), and IL-10 (7.5 ± 6.8 vs 16.8 ± 19.2 pg/mL,
< 0.01), whereas no differences were observed in serum.
Results suggest that (1) inflammatory mediators play a minor role in the maintenance of chronic pain in contrast to initiation of acute pain, (2) chemokines/cytokines are downregulated in chronic pain, or (3) chemokines/cytokines have a protective role for nerve regeneration that is disturbed in patients with chronic pain.
Stratification of patients according to the individual sensory phenotype has been suggested a promising method to identify responders for pain treatment. However, many state-of-the-art sensory ...testing procedures are expensive or time-consuming.
Therefore, this study aimed to present a selection of easy-to-use bedside devices.
In total, 73 patients (39 m/34 f) and 20 controls (11 m/9 f) received a standardized laboratory quantitative sensory testing (QST) and a bedside-QST. In addition, 50 patients were tested by a group of nonexperienced investigators to address the impact of training. The sensitivity, specificity, and receiver-operating characteristics were analyzed for each bedside-QST parameter as compared to laboratory QST. Furthermore, the patients' individual sensory phenotype (ie, cluster) was determined using laboratory QST, to select bedside-QST parameters most indicative for a correct cluster allocation.
The bedside-QST parameters "loss of cold perception to 22°C metal," "hypersensitivity towards 45°C metal," "loss of tactile perception to Q-tip and 0.7 mm CMS hair," as well as "the allodynia sum score" indicated good sensitivity and specificity (ie,
70%). Results of interrater variability indicated that training is necessary for individual parameters (ie, CMS 0.7). For the cluster assessment, the respective bedside quantitative sensory testing (QST) parameter combination indicated the following agreements as compared to laboratory QST stratification: excellent for "sensory loss" (area under the curve AUC = 0.91), good for "thermal hyperalgesia" (AUC = 0.83), and fair for "mechanical hyperalgesia" (AUC = 0.75).
This study presents a selection of bedside parameters to identify the individual sensory phenotype as cost and time efficient as possible.
Pain is a common symptom accompanying the coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Nonspecific discomfort such as sore throat ...and body ache are frequent. Parainfectious pain such as headache, myalgia, or neuropathic pain has also been reported. The latter seems to be associated with an autoimmune response or an affection of the peripheral neuromuscular system or the central nervous system because of the viral infection. Furthermore, chronic pain can be a complication of intensive care unit treatment due to COVID-19 itself (such as intensive care-acquired weakness) or of secondary diseases associated with the SARS-CoV-2 infection, including Guillain-Barré syndrome, polyneuritis, critical illness polyneuropathy, or central pain following cerebrovascular events. Data on long-lasting painful symptoms after clinically manifest COVID-19 and their consequences are lacking. In addition, preexisting chronic pain may be exacerbated by limited and disrupted health care and the psychological burden of the COVID-19 pandemic. Medical providers should be vigilant on pain during and after COVID-19.
Patients suffering from fibromyalgia syndrome (FMS) are heterogenous. They often present with sensory abnormalities and comorbidities.
We aimed to answer the following questions: (1) Is there a ...specific somatosensory profile in our patient cohort? (2) Can we detect subgroups characterized by a specific combination of sensory and psychological features? and (3) Do psychological parameters influence sensory signs?
In 87 patients with FMS quantitative sensory testing was performed on the hand and evaluated in combination with questionnaire results regarding pain, psychological comorbidities, sleep, and functionality.
Patients presented different somatosensory patterns, but no specific subgroups regarding sensory signs and psychological features were detected. Hypersensitivity for noxious mechanical and thermal stimuli and hyposensitivity for nonnoxious mechanical stimuli were the most prominent features. Thirty-one percent of patients showed signs of central sensitization as indicated by abnormally increased pinprick hyperalgesia or dynamic mechanical allodynia. Central sensitization was associated with higher pain intensities (
< 0.001). Only a small influence of psychiatric comorbidities on mechanical pain sensitivity (
= 0.044) and vibration detection (
= 0.028) was found, which was partly associated with high pain intensities. A small subgroup of patients (11.4%) demonstrated thermal hyposensitivity (loss of small-fiber function).
Patients with FMS showed various somatosensory abnormalities. These were not significantly influenced by psychological comorbidities. Signs for central sensitization were detected in about one-third of patients and associated with higher pain intensities. This supports the notion of central sensitization being a major pathophysiological mechanism in FMS, whereas small-fiber loss may be less important.
Fabry disease frequently includes pain as an early disease feature, which was characterized as a dysfunctional processing of somatosensory information in various studies. The pathomechanism involves ...the mutation in the x-chromosomal GLA-gene and a consequent reduction of the α-galactosidase. This results in an insufficient reduction of globotriaosylceramide (GL3). Interestingly, an accumulation of GL3 was shown in both vascular endothelial cells and nerve tissue. This implicates that both an endothelial and nerve-dependent dysfunction may be considered as prominent mechanisms in pain pathogeneses.
The exploration of endothelial and C-fiber-dependent microcirculatory changes was conducted in a healthy cohort (
= 22) and in patients with polyneuropathy (
= 21) and Fabry disease (
= 15). Microcirculatory measurements were conducted using a laser speckle contrast analysis (LASCA) in combination with a thermoprobe controlling system, which applied a constant heat stimulus (42°C). Additionally, nerve fiber function was assessed via Quantitative Sensory Testing and heart rate variability (HRV).
The results indicated a characteristic perfusion profile in the control group as well as both patient groups. Fabry patients had the smallest increase of endothelial-dependent perfusion as compared to the others % increase as compared to Fabry: control + 129% (
= 0.002), PNP + 126% (
= 0.019). The sensory testing indicated a dysfunctional processing of A-delta fibers in Fabry disease as compared to healthy controls cold detection threshold (CDT):
= 0.004, mechanical pain threshold (MPT):
= 0.007 and PNP patients (MPT:
= 0.001).
Our results point to both an endothelial and a nerve-dependent dysfunction in Fabry disease. Therefore, not only direct changes in nerve fiber tissue may contribute to an altered sensory processing. Indeed, evidence of a perfusion change in vasa nervorum could also contribute to the dysfunctional processing of sensory information, which likely occurs under physical stress.
C-fibers express transient receptor potential (TRP) channels. These high-voltage gated channels function as integrators of different physical stresses (e.g. heat, protons, ATP). Additionally channel ...activation can be induced by capsaicin. Topically applied, capsaicin elicits burning pain, heat and mechanical hyperalgesia and serves as a human surrogate model for pain. It was suggested that the TRPV1-variant rs8065080 (1911A>G) plays a pivotal role in patients with neuropathic pain syndromes. We investigated the effect of this TRPV1-SNP on thermal sensitivity and superficial skin perfusion in 25 healthy subjects.
Nine subjects being homozygous TRPV1 wild type (AA), 8 heterozygous (AG) and 8 homozygous variant (GG) carriers were selected out of a pool of genotyped healthy individuals. Under physiological conditions (no capsaicin application), there was no statistical significant difference in thermal thresholds or skin perfusion between carriers of different TRPV1 1199A>G genotypes. However, intra-individual calculations (Δ% pre vs. post capsaicin) revealed (1) less warm-detection in AA/AG (-82.1%) compared to GG (-13.1%) and (2) a gain of heat pain sensitivity in AA/AG (+22.2%) compared to GG carriers (+15.6%) after adjustment for perfusion measurements ((1)p = 0.009, (2)p = 0.021).
Presence of homozygous variant TRPV1 genotype (GG) demonstrated less capsaicin-induced warm hypoesthesia in warm-detection and less capsaicin-induced heat pain sensitivity suggesting an altered channel function. This demonstrates not only the functional influence of TRPV1 rs8065080 polymorphism itself; it further more underpins the relevance of genotyping-based approaches in both patients and surrogate models of neuropathic pain in healthy volunteers.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background and Aims
Healthy women have generally been found to have increased experimental pain perception and chronic pain has a higher prevalence in female as compared to male patients. However, no ...study has investigated whether pain intensity and pain perception thresholds are distinct or similar between sexes within various chronic pain entities. We investigated whether average pain intensities and pain thresholds assessed using quantitative sensory testing (QST) differed between women and men suffering from three distinct chronic pain conditions: Complex Regional Pain Syndrome (CRPS type I), peripheral nerve injury (PNI) or polyneuropathy (PNP), as compared to paired healthy volunteers.
Methods
QST data of 1,252 patients (669 female, 583 male) with PNI (n = 342), PNP (n = 571) or CRPS (n = 339), and average pain intensity reports from previously published studies were included. Absolute and z‐values (adjusted for age and body region) of cold, heat, pressure (PPT) and pinprick pain thresholds were compared in generalized linear models with aetiology, duration of underlying pain disease and average pain intensity as fixed effects.
Results
Average pain intensity during the past four weeks did not differ between women and men, in both mean and range. In women absolute pain thresholds for cold, heat and pinprick were lower than in males across all diagnoses (p < .05). However, after z‐transformation these differences disappeared except for PPT in CRPS (p = .001).
Discussion
Pain thresholds in patients show only minor sex differences. However, these differences mimic those observed in healthy subjects and do not seem to be linked to specific pathophysiological processes.
Significance
Female healthy participants and female patients with neuropathic pain conditions or CRPS I report lower pain thresholds compared to males, but pain intensity is similar and there is no sex difference in the extent to which the thresholds are altered in neuropathic pain or CRPS. Thus, the sex differences observed in various chronic pain conditions mimic those obtained in healthy participants, indicating that these differences are not linked to specific pathophysiological processes and are of minor clinical relevance.
Fabry disease (FD) causes cold-evoked pain and impaired cold perception through small fiber damage, which also occurs in polyneuropathies (PNP) of other origins. The integrity of thinly myelinated ...fibers and the spinothalamic tract is assessable by cold-evoked potentials (CEPs). In this study, we aimed to assess the clinical value of CEP by investigating its associations with pain, autonomic measures, sensory loss, and neuropathic signs.
CEPs were examined at the hand and foot dorsum of patients with FD (
= 16) and PNP (
= 21) and healthy controls (
= 23). Sensory phenotyping was performed using quantitative sensory testing (QST). The painDETECT questionnaire (PDQ), FabryScan, and measures for the autonomic nervous system were applied. Group comparisons and correlation analyses were performed.
CEPs of 87.5% of the FD and 85.7% of the PNP patients were eligible for statistical analysis. In all patients combined, CEP data correlated significantly with cold detection loss, PDQ items, pain, and autonomic measures. Abnormal CEP latency in FD patients was associated with an abnormal heart frequency variability item (
= -0.684; adjusted
= 0.04). In PNP patients, CEP latency correlated significantly with PDQ items, and CEP amplitude correlated with autonomic measures (
= 0.688, adjusted
= 0.008;
= 0.619, adjusted
= 0.024). Furthermore, mechanical pain thresholds differed significantly between FD (gain range) and PNP patients (loss range) (
= 0.01).
Abnormal CEPs were associated with current pain, neuropathic signs and symptoms, and an abnormal function of the autonomic nervous system. The latter has not been mirrored by QST parameters. Therefore, CEPs appear to deliver a wider spectrum of information on the sensory nervous system than QST alone.
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