BACKGROUND: Pain thresholds and primary headaches, including cluster headache attacks, have circadian rhythmicity. Thus, they might share a common neuronal mechanism.
OBJECTIVE: This study aimed to elucidate how the modulation of nociceptive input in the brainstem changes from noon to midnight. Insights into the mechanism of these fluctuations could allow for new hypotheses about the pathophysiology of cluster headache.
METHODS: This repeated measure observational study was conducted at the University Hospital Zurich from December 2019 to November 2022. Healthy adults between 18 and 85 years of age were eligible. All participants were examined at noon and midnight. We tested the pain threshold on both sides of the foreheads with quantitative sensory testing, assessed tiredness levels, and obtained high-field (7 Tesla) and high-resolution functional magnetic resonance imaging (MRI) at each visit. Functional connectivity was assessed at the two visits by performing a region-of-interest analysis. We defined nuclei in the brainstem implicated in processing nociceptive input as well as the thalamus and suprachiasmatic nucleus as the region-of-interest.
RESULTS: Ten people were enrolled, and seven participants were included. First, we did not find statistically significant differences between noon and midnight of A-delta-mediated pain thresholds (median mechanical pain threshold at noon: left 9.2, right 9.2; at night: left 6.5, right 6.1). Second, after correction for a false discovery rate, we found changes in the mechanical pain sensitivity to have a statistically significant effect on changes in the functional connectivity between the left parabrachial nucleus and the suprachiasmatic nucleus (T = -40.79).
CONCLUSIONS: The MRI data analysis suggested that brain stem nuclei and the hypothalamus modulate A-delta-mediated pain perception; however, these changes in pain perception did not lead to statistically significantly differing pain thresholds between noon and midnight. Hence, our findings shed doubt on our hypothesis that the physiologic circadian rhythmicity of pain thresholds could drive the circadian rhythmicity of cluster headache attacks.

Offset analgesia (OA) is believed to reflect the efficiency of the endogenous pain modulatory system. However, the underlying mechanisms are still being debated. Previous research suggested both, central and peripheral mechanisms, with the latter involving the influence of specific A-delta-fibers. Therefore, this study aimed to investigate the influence of a non-ischaemic A-fiber conduction blockade on the OA response in healthy participants. A total of 52 participants were recruited for an A-fiber conduction blockade via compression of the superficial radial nerve. To monitor fiber-specific peripheral nerve conduction capacity, quantitative sensory testing was performed continuously. Before, during and after the A-fiber block, an individualized OA-paradigm was applied to the dorsum of both hands (blocked and control side were randomized). Pain intensity of each heat stimulus was evaluated by an electronic visual analogue scale. A successful A-fiber conduction blockade was achieved in thirty participants. Offset analgesia has been verified within time (before, during, after blockade), and condition (blocked and control side) (p < 0.01, d > 0.5). Repeated measurements ANOVA showed no significant interaction effects between OA within condition and time (p = 0.24, η²p = 0.05). Hence, no significant effect of A-fiber blockade was detected on OA during noxious heat stimulation. The results suggest that peripheral A-fiber afferents may play a minor role in OA compared to alternative central mechanisms or other fibers. However, further studies are needed to substantiate a central rather than peripheral influence on OA. PERSPECTIVE: This article presents the observation of offset analgesia before, during and after a successful A-fiber conduction blockade in healthy volunteers. A better understanding of the mechanisms of offset analgesia and endogenous pain modulation in general may help to explain the underlying aspects of pain disorders.

UNASSIGNED: Notalgia paresthetica (NP) is a chronic condition characterized by pruritus and other unpleasant dysesthetic sensations unilaterally on the subscapular back. Its specific underlying mechanisms are largely unknown, though hypothesized to be neuropathic. Determination of possible somatosensory contributors to the condition could pave the way for novel treatments.
UNASSIGNED: Given the potential involvement of non-pruritic mechanisms in NP, our objective was to broadly characterize the somatosensory function in NP-affected and unaffected skin using methods that have been standardized in pain-free controls and painful neuropathic disorders. We hypothesized that if NP is caused by neuropathic mechanisms not targeted directly to pruritoceptors in the skin, somatosensory abnormalities would not be itchspecific. Second, given the lack of symptoms on the contralateral side of the back, we hypothesized that this region would be normally sensitive.
UNASSIGNED: In this study, quantitative sensory testing (QST) was used to comprehensively assess the somatosensory function in 15 adult patients with NP. Standardized QST metrics were performed in the NP-affected region and compared with the contralateral asymptomatic skin and itch-free individuals using an age, gender, and site-matched reference data set.
UNASSIGNED: There were no significant differences in sensitivity between symptomatic and asymptomatic skin, except for increased mechanical-evoked itch on the itchy side. However, reference data set comparisons revealed bilateral hyposensitivity to innocuous cold and noxious pinprick and higher temporal summation of pain in patients with NP. In addition, compared with reference data, patients with NP demonstrated decreased sensitivity to cold and pinprick, presence of paradoxical heat sensations, and increased wind-up of pain.
UNASSIGNED: These results suggest a role for Aδ fiber pathways and central sensitization in NP-associated itch. More research is needed to determine whether sensory differences extend beyond the NP-affected dermatomal level and what might cause neuropathy specifically targeting Aδ fibers.

BACKGROUND: In clinical practice, the implementation of tailored treatment is crucial for assessing the patient\'s emotional processing profile. Here, we investigate all three levels of analysis characterizing emotion processing, i.e., recognition, representation, and regulation, in patients with peripheral neuropathic pain (PNP).
METHODS: Sixty-two patients and forty-eight healthy controls underwent quantitative sensory testing, i.e., psychophysical tests to assess somatosensory functions such as perception of cold (CDT), heat-induced pain (HPT), and vibration (VDT), as well as three standardized tasks to assess emotional processing: (1) the Ekman 60-Faces Test (EK-60F) to assess recognition of basic facial emotions, (2) the Reading the Mind in the Eyes Test (RME) to assess the ability to represent the feelings of another person by observing their eyes, and (3) the 20-item Toronto Alexithymia Scale (TAS-20) to assess emotional dysregulation, i.e., alexithymia.
RESULTS: General Linear Model analysis revealed a significant relationship between left index finger VDT z-scores in PNP patients with alexithymia. The RME correlated with VDT z-scores of the left little finger and overall score for the EK-60F.
CONCLUSIONS: In patients with PNP, emotion processing is impaired, which emphasizes the importance of assessing these abilities appropriately in these patients. In this way, clinicians can tailor treatment to the needs of individual patients.

OBJECTIVE: To assess the impact of endoscope-assisted fractured roots or fragments extraction within the mandibular canal, along with quantitative sensory testing (QST) alterations in the inferior alveolar nerve (IAN).
METHODS: Six patients with lower lip numbness following mandibular third molar extraction were selected. All patients had broken roots or fragments within the mandibular canal that were extracted under real-time endoscopic assistance. Follow-up assessments were conducted on postoperative days 1, 7, and 35, including a standardized QST of the lower lip skin.
RESULTS: The average surgical duration was 32.5 min, with the IAN exposed in all cases. Two of the patient exhibited complete recovery of lower lip numbness, three experienced symptom improvement, and one patient remained unaffected 35 days after the surgery. Preoperative QST results showed that the mechanical detection and pain thresholds on the affected side were significantly higher than those on the healthy side, but improved significantly by postoperative day 7 in five patients, and returned to baseline in two patients on day 35. There were no significant differences in the remaining QST parameters.
CONCLUSIONS: All endoscopic surgical procedures were successfully completed without any additional postoperative complications. There were no cases of deterioration of IAN injury, and lower lip numbness recovered in the majority of cases. Endoscopy allowed direct visualization and examination of the affected nerve, facilitating a comprehensive analysis of the IAN.

暂无摘要。

OBJECTIVE: The aim of this study was to validate the Neuropathic Pain for Post-Surgical Patients (NeuPPS) scale against clinically verified neuropathic pain (NP) by quantitative sensory testing (QST) as well as evaluation of other psychometric properties. The NeuPPS is a validated 5-item scale designed to evaluate NP in surgical populations.
METHODS: Data from 537 women aged >18 years scheduled for primary breast cancer surgery enrolled in a previous study for assessing risk factors for persistent pain after breast cancer treatment were used. Exclusion criteria were any other breast surgery or relevant comorbidity. A total of 448 eligible questionnaires were available at 6 months and 455 at 12 months. At 12 months, 290 patients completed a clinical examination and QST. NeuPPS and PainDETECT were analyzed against patients with and without clinically verified NP. NP was assessed using a standardized QST protocol including a clinical assessment. Furthermore, the NeuPPS and PainDETECT scores were psychometrically tested with an item response theory method, the Rasch analysis, to assess construct validity. Primary outcomes were the diagnostic accuracy measures for the NeuPPS, and secondary measures were psychometric analyses of the NeuPPS after 6 and 12 months. PainDETECT was also compared to clinically verified NP as well as NeuPPS comparing the stability of the estimates.
RESULTS: Comparing the NeuPPS scores with verified NP using a receiver operating characteristic curve, the NeuPPS had an area under the curve of 0.80. Using a cutoff of 1, the NeuPPS had a sensitivity of 88% and a specificity of 59%, and using a cutoff of 3, the values were 35 and 96%, respectively. Analysis of the PainDETECT indicated that the used cutoffs may be inappropriate in a surgical population.
CONCLUSIONS: The present study supports the validity of the NeuPPS as a screening tool for NP in a surgical population.

UNASSIGNED: The mechanisms underlying persistent scar pain are not fully elucidated and evidence for the clinical evaluation of scar pain is limited. This pilot observational study investigated participation data and sought to identify objective clinical scar evaluation measures for future trials.
UNASSIGNED: With ethical approval and consent, adults undergoing planned hand surgery were enrolled from one NHS hospital. At 1- and 4-months post-surgery scar thermal and mechanical pain thresholds were evaluated with quantitative sensory testing; peri-scar inflammation with infrared thermometry and pliability with durometry. Participation data were analysed with descriptive statistics; the association of clinical measures with patient reported scar pain was analysed.
UNASSIGNED: Twenty-one participants (22% eligible patients) enrolled before study closure due to the COVID-19 pandemic; 13 completed follow up. No adverse events or dropouts resulted from clinical scar evaluation. Seventy percent of participants reported undertaking topical, nonprescription scar treatment independently. Neuropathic Pain Symptom Inventory (NPSI) scores were dispersed across the score range, capturing variability in participant-reported scar symptoms. Scar morphology, pliability and inflammation were not associated with scar pain. Differences between scar and contralateral skin in thermal and mechanical pain sensitivity were identified.
UNASSIGNED: People with acute hand scars participate in clinical research and independently initiate scar treatment. Clinical testing of acute post-surgical hand scars is well tolerated. The NPSI demonstrates utility for exploring scar pain symptoms and may support the elucidation of mechanisms of persistent scar pain. Clinical tests of thermal and mechanical and sensitivity are promising candidate clinical measures of scar pain for future trials.
UNASSIGNED: Background: it is unknown why some scars remain painful long-term. We do not know if scar flexibility, inflammation or sensitivity to temperature or pressure relate to scar pain. We investigated if patients would enrol in scar research, if scar testing was tolerated and if clinical tests are useful for future scar studies. Study conduct: with ethical approval and consent, adult hand surgery patients were enrolled from one NHS hospital. Scar pain, inflammation and response to thermal, sharp and pressure tests were assessed at 1- and 4-months after surgery. Statistically, we analysed study participation, tolerance for clinical scar tests and if the scar tests related to scar pain. Findings: 21 participants (22% eligible patients) enrolled before study closure due to the COVID-19 pandemic; 13 completed follow up. No participants were injured due to scar testing. 70% of participants reported treating their scar independently. Neuropathic Pain Symptom Inventory (NPSI) allows participants to give a broad range of answers about their scar symptoms. Scores for clinical tests of scar flexibility and inflammation did not relate to participant-reported scar pain. Scars were more sensitive to tests of pin prick and cold than unaffected skin. What we learned: people with new hand scars participate in research and independently initiate scar treatment. Clinical testing of post-surgical hand scars is well tolerated. The NPSI is useful for exploring scar pain symptoms and may help us to learn about persistent scar pain. Pinprick and cold clinical tests may be useful objective pain tests for future scar research.

Migraine is a chronic neurological disorder that involves the brain, characterized by a series of abnormal neuronal networks interacting at different levels of the central and peripheral nervous system. Furthermore, it is known that psychosocial features contribute to the exacerbation and chronicity of symptoms.
To compare the somatosensory and psychosocial profiles of migraine patients with a control group.
We conducted a cross-sectional study comparing the somatosensory and psychosocial profiles of patients with migraine and healthy volunteers. A total of 52 women were included. For the somatosensory profile, Mechanical Detection Threshold (MDT), Pressure Pain Threshold (PPT), Temporal Summation (TS), and Conditioned Pain Modulation (CPM) in the trigeminal and extra-trigeminal areas were evaluated. Psychosocial profiles were assessed using questionnaires, the Central Sensitization Inventory, the Generalized Anxiety Disorders, the Pain Catastrophizing Scale, and the Tampa Scale of Kinesiophobia. Mann-Whitney U test was used to compare differences in the profiles between groups. The significance level was set at 5%.
Migraine patients showed a loss of somatosensory function in the trigeminal area for MDT (p = 0.019, r = 0.34 and p = 0.011, r = 0.37 for the ophthalmic nerve and masseter muscle respectively), lower PPT in trigeminal and extra-trigeminal areas (p < 0.001, r=>0.60) and less efficient CPM (p < 0.001, r=>0.60). No statistically significant differences were found in the TS (p=>0.05). Statistically significant differences were found in all psychosocial variables (p = <0.001 r=>0.60).
Migraine patients showed loss of somatosensory function, lower pressure pain threshold, and an inhibitory pro-nociceptive profile with high scores on central sensitization and fear of movement compared to the control group.

OBJECTIVE: We aimed to investigate to what extent small fiber tests were abnormal in an unselected retrospective patient material with symptoms suggesting that small fiber neuropathy (SFN) could be present, and to evaluate possible gender differences.
METHODS: Nerve conduction studies (NCS), skin biopsy for determination of intraepidermal nerve fiber density (IENFD) and quantitative sensory testing (QST) were performed. Z-scores were calculated from reference materials to adjust for the effects of age and gender/height.
RESULTS: Two hundred and three patients, 148 females and 55 males had normal NCS and were considered to have possible SFN. 45.3 % had reduced IENFD, 43.2 % of the females and 50.9 % of the males. Mean IENFD was 7.3 ± 2.6 fibers/mm in females and 6.1 ± 2.3 in males (p<0.001), but the difference was not significant when adopting Z-scores. Comparison of gender differences between those with normal and abnormal IENFD were not significant when Z-scores were applied. QST was abnormal in 50 % of the patients (48.9 % in females and 52.9 % in males). In the low IENFD group 45 cases out of 90 (50 %) were recorded with abnormal QST. In those with normal IENFD 51 of 102 (50 %) showed abnormal QST.
CONCLUSIONS: Less than half of these patients had reduced IENFD, and 50 % had abnormal QST. There were no gender differences. A more strict selection of patients might have increased the sensitivity, but functional changes in unmyelinated nerve fibers are also known to occur with normal IENFD. Approval to collect data was given by the Norwegian data protection authority at University Hospital of North Norway (Project no. 02028).