Differential Expression of microRNAs in Serum of Patients with Chronic Painful Polyneuropathy and Healthy Age-Matched Controls.

Polyneuropathies (PNP) are the most common type of disorder of the peripheral nervous system in adults. However, information on microRNA expression in PNP is lacking. Following microRNA sequencing, we compared the expression of microRNAs in the serum of patients experiencing chronic painful PNP with healthy age-matched controls. We have been able to identify four microRNAs (hsa-miR-3135b, hsa-miR-584-5p, hsa-miR-12136, and hsa-miR-550a-3p) that provide possible molecular links between degenerative processes, blood flow regulation, and signal transduction, that eventually lead to PNP. In addition, these microRNAs are discussed regarding the targeting of proteins that are involved in high blood flow/pressure and neural activity dysregulations/disbalances, presumably resulting in PNP-typical symptoms such as chronical numbness/pain. Within our study, we have identified four microRNAs that may serve as potential novel biomarkers of chronic painful PNP, and that may potentially bear therapeutic implications.

The pandemic's effect on a patient cohort with painful polyneuropathy in 2020: A longitudinal study on pain, mood, and everyday life.

In the early phase of the COVID pandemic 2020, we demonstrated how patients with painful polyneuropathy, against our expectations, did not experience a deterioration of their neuropathic pain. We hypothesized that our assessed measures, that is, pain intensity and characteristics, emotional wellbeing, and everyday life, would deteriorate in the further course of the pandemic according to the phases of disaster management. Thus, the aim of our study was to investigate patients repeatedly under varying pandemic conditions from March until December 2020. Sixty-three patients were investigated with validated questionnaires (brief pain inventory [BPI], neuropathic pain symptom inventory [NPSI], pain catastrophizing scale [PCS], patient-reported outcomes measurement information system [PROMIS] pain interference/sleep disturbance/fatigue/ depression/anxiety, EuroQol 5 dimensions 5 level version [EQ-5D-5L]) and a pandemic-specific, self-designed questionnaire. The data from the beginning of the pandemic with severe restrictions, during summer with loosened regulations and from December 2020 with reinstalled, severe restrictions were compared with an observational design. Patients reported higher pain severity when restrictions were lower. Sleep, mood, and quality of life did not change in the course of the pandemic in the validated measures. Pain interference significantly decreased during the study independent from restrictions. Patients who reported medical disadvantages had a lower quality of life upon EuroQol 5 dimension (EQ-5D) and were significantly more worried about their health. The perception of pain intensity was dependent on pandemic severity. Sleep, mood, and quality of life did not change significantly in validated measures. Continued medical care seems decisive to prevent worsening of pain and quality of life.

A modality-specific somatosensory evoked potential test protocol for clinical evaluation: A feasibility study.

OBJECTIVE: We aimed to establish an objective neurophysiological test protocol that can be used to assess the somatosensory nervous system. METHODS: In order to assess most fiber subtypes of the somatosensory nervous system, repetitive stimuli of seven different modalities (touch, vibration, pinprick, cold, contact heat, laser, and warmth) were synchronized with the electroencephalogram (EEG) and applied on the cheek and dorsum of the hand and dorsum of the foot in 21 healthy subjects and three polyneuropathy (PNP) patients. Latencies and amplitudes of the modalities were assessed and compared. Patients received quantitative sensory testing (QST) as reference. RESULTS: We found reproducible evoked potentials recordings for touch, vibration, pinprick, contact-heat, and laser stimuli. The recording of warm-evoked potentials was challenging in young healthy subjects and not applicable in patients. Latencies were shortest within Aß-fiber-mediated signals and longest within C-fibers. The test protocol detected function loss within the Aß-fiber and Aδ-fiber-range in PNP patients. This function loss corresponded with QST findings. CONCLUSION: In this pilot study, we developed a neurophysiological test protocol that can specifically assess most of the somatosensory modalities. Despite technical challenges, initial patient data appear promising regarding a possible future clinical application. SIGNIFICANCE: Established and custom-made stimulators were combined to assess different fiber subtypes of the somatosensory nervous system using modality-specific evoked potentials.

Revealing the time course of laser-evoked potential habituation by high temporal resolution analysis.

BACKGROUND AND OBJECTIVES: Reduced laser-evoked potential (LEP) habituation indicates abnormal central pain processing. But the paradigm (four stimulation blocks a 25 stimuli) is time consuming and potentially omits important information on the exact habituation time course. This study examined whether a high temporal resolution (HTR) analysis (dividing the four stimulation blocks into 12 analysis blocks) can answer the following questions: (a) After how many stimuli does LEP habituation occur? (b) Is there a difference in LEP habituation in younger versus older subjects? (c) Is HTR applicable on radiculopathy patients? METHODS: EEG data of 129 subjects were included. Thirty-four young healthy and 28 advanced-aged healthy subjects were tested with LEPs on the hand dorsum. Thirty-seven radiculopathy patients and 30 controls were tested with LEPs on the L3 dermatome. The EEG data of the hand dorsa have been analysed conventionally and with HTR analysis. The applicability of HTR has been tested on radiculopathy patients and respective controls. RESULTS: HTR was well feasible in young healthy subjects and revealed a strong habituation effect during the first 25 stimuli (i.e. within the first 5 min). After approximately 48 stimuli, no further significant habituation was detectable. LEP amplitudes were higher in young subjects. HTR was unsuitable for elderly subjects and middle-aged radiculopathy patients. CONCLUSIONS: In young healthy subjects, HTR allows a shortening of the test protocol while providing a detailed information on the time course of LEP habituation. A shorter protocol might be useful for the applicability of the LEP paradigm for clinical and experimental settings as well as pharmacological studies. SIGNIFICANCE: The usage of high temporal resolution (HTR) analysis in young healthy subjects enables a short test protocol and provides the exact time course of laser-evoked potential habituation. This can be useful for the examination of neurological conditions affecting younger patients and for pharmacological studies. HTR was inapplicable in advanced-aged subjects and patients with radiculopathy.

The serotonin receptor 2A (HTR2A) rs6313 variant is associated with higher ongoing pain and signs of central sensitization in neuropathic pain patients.

BACKGROUND: The serotonin receptor 2A (HTR2A) has been described as an important facilitation mediator of spinal nociceptive processing leading to central sensitization (CS) in animal models of chronic pain. However, whether HTR2A single nucleotide variants (SNVs) modulate neuropathic pain states in patients has not been investigated so far. The aim of this study was to elucidate the potential association of HTR2A variants with sensory abnormalities or ongoing pain in neuropathic pain patients. METHODS: At total of 240 neuropathic pain patients and 253 healthy volunteers were included. Patients were phenotypically characterized using standardized quantitative sensory testing (QST). Patients and controls were genotyped for HTR2A g.-1438G > A (rs6311) and c.102C > T (rs6313). Genotype-related differences in QST parameters were assessed considering QST profile clusters, principal somatosensory components and sex. RESULTS: There was an equal distribution of rs6313 and linked rs6311 between patients and controls. However, the rs6313 variant was significantly associated with a principal component of pinprick hyperalgesia and dynamic mechanical allodynia, indicating enhanced CS in patients with sensory loss (-0.34 ± 0.15 vs. +0.31 ± 0.11 vs., p < .001). In this cluster, the variant allele was also associated with single QST parameters of pinprick hyperalgesia (MPT, +0.64 ± 0.18 vs. -0.34 ± 0.23 p = .002; MPS, +0.66 ± 0.17 vs. -0.09 ± 0.23, p = .009) and ongoing pain was increased by 30%. CONCLUSIONS: The specific association of the rs6313 variant with pinprick hyperalgesia and increased levels of ongoing pain suggests that the HTR2A receptor might be an important modulator in the development of CS in neuropathic pain. SIGNIFICANCE: This article presents new insights into serotonin receptor 2A-mediating mechanisms of central sensitization in neuropathic pain patients. The rs6313 variant allele was associated with increased mechanical pinprick sensitivity and increased levels of ongoing pain supporting a contribution of central sensitization in the genesis of ongoing pain providing a possible route for mechanism-based therapies.

The early influence of COVID-19 pandemic-associated restrictions on pain, mood, and everyday life of patients with painful polyneuropathy.

INTRODUCTION: The SARS-Cov-2 pandemic requires special attention on its psychological effects and the impact on patients with chronic pain. OBJECTIVES: This study aimed at examining the influence of the COVID-19 pandemic-associated regulations initiated by the German government on pain intensity and characteristics, emotional well-being, and everyday life of patients with painful polyneuropathy. METHODS: Forty-three patients (well assessed with questionnaires before the pandemic and without change of their health status between baseline and current assessment) were investigated with validated, self-reported questionnaires and COVID-19-specific items 2 weeks after the regulations came into effect. RESULTS: Pain intensity remained stable or even improved like the neuropathic pain symptom inventory total score (t0: 33.54 ± 20.48 vs t1: 27.38 ± 16.16, P = 0.008). Only 11.6% reported a pandemic-associated pain worsening. Rumination scores of the Pain Catastrophizing Scale were lower during t1 compared to before the pandemic regulations (t0: 7.81 ± 4.70, t1: 6.49 ± 4.39; P = 0.030). Interestingly, pain ratings for the last 7 days were higher in patients with a changed social life compared to those without (-1.63 ± 1.60 vs 0.31 ± 1.83; P = 0.01). Quality of life was decreased and helplessness increased in those with higher pain ratings. CONCLUSION: Results suggest a shift of attention from the chronic pain condition towards the imminent threat of a global pandemic. As the impacts of the pandemic are persistent and evolving, the development of the measured parameters in the forthcoming weeks will be of great interest.