Pinprick Stimuli Research Articles

Preoperative susceptibility to developing secondary hyperalgesia is associated with post-thoracotomy pain at 2 months.

Identifying the subset of patients at risk for developing persistent pain after surgery is clinically important as they could benefit from targeted prevention measures. In this prospective study, we investigated if the preoperative assessment of the individual susceptibility to developing experimentally induced secondary hyperalgesia is associated with post-thoracotomy pain at 2 months. Forty-one patients scheduled to undergo a posterolateral thoracotomy were recruited before surgery and followed prospectively for 2 months. The day before surgery, we experimentally induced secondary hyperalgesia at one of the two forearms and measured the change of perception to mechanical pinprick stimuli and the area of hyperalgesia. On postoperative Day 4, Day 15 and at the 2-month follow-up, patients were asked about their pain intensity at rest and during coughing and the area of secondary hyperalgesia around the scar as well as the change in perception to mechanical pinprick stimuli was measured. Of the 41 patients that were recruited only 20 could be analysed. Forty per cent reported pain at the 2-month follow-up. All of them reported cough-evoked pain and 10 per cent also reported pain at rest. A binary logistic regression model with both the magnitude and extent of experimentally induced secondary hyperalgesia was statistically significant (chi-squared = 12.439, p = 0.002, McFadden R2 = 0.462) and showed excellent discriminative power (AUC = 0.938) for the presence or absence of cough-evoked pain at the 2 month follow-up. Our findings indicate that the individual susceptibility to developing experimentally induced secondary hyperalgesia preoperatively may identify patients who are potentially vulnerable to develop persistent post-thoracotomy pain. Our data suggests that preoperatively assessed experimentally induced secondary hyperalgesia displays excellent discriminative power for the presence or absence of cough-evoked pain 2 months after thoracotomy.

Effect of limb position change on capsaicin-evoked pain: Evidence of interplays between the vascular and nociceptive systems?

This experiment aimed at confirming our incidental observation that, when capsaicin is applied on the volar forearm, raising the arm to a vertical position leads to a dramatic increase in capsaicin-evoked pain and to explore possible underlying mechanisms. Twenty healthy volunteers received a 2% capsaicin patch on one forearm and a vehicle patch on the other. Patches were kept in place for 60 min. The perception caused by the patch was assessed repeatedly before, during and after patch application, both with the arm in horizontal resting position and raised vertically. In addition, capsaicin-induced secondary hyperalgesia was assessed using mechanical pinprick stimuli. Half of the participants were seated upright while the other half were lying supine, to assess whether the effect of limb position on capsaicin-evoked pain was due to gravity. After a few minutes of patch application, raising the capsaicin-treated arm (but not the vehicle-treated arm) led to a strong increase of the pain experienced at the patch. This effect of raising the arm did not differ between participants in the supine and seated groups and is therefore likely related to the position of the arm relative to the ground rather than to the body. Mechanical secondary hyperalgesia and the arm raising effect were strongly decorrelated at the last time point after patch removal, indicating different underlying mechanisms. Our results indicate that capsaicin-evoked pain can be strongly modulated by limb posture and that this effect may be caused by an interplay between vascular and nociceptive systems. Capsaicin-evoked pain can be strongly modulated by limb posture and this effect may be caused by an interplay between vascular and nociceptive systems.

Signs of hyperpathia in chronic peripheral neuropathic pain.

Neuropathic pain is pain due to a disease or lesion of the somatosensory system, and can be either spontaneous, evoked or both. Hyperpathia is a type of evoked pain defined by IASP as 'a painful syndrome characterized by an abnormally painful reaction to a stimulus, especially a repetitive stimulus, as well as an increased threshold'. The literature is sparse, and definitions are unclear and inconsistent. The aim of this study was to examine for the presence of mechanical hyperpathia in a heterogeneous group of patients with peripheral neuropathic pain and correlate signs of hyperpathia with other sensory signs. Patients were examined with graded pinprick stimuli to obtain a stimulus-response curve and repetitive pinprick stimuli to assess increase in pain over time and aftersensations. Then, patients were grouped based on the likelihood of having mechanical hyperpathia with either a steep stimulus-response curve or a steep curve on the repetitive pinprick test and results were correlated to mechanical detection and pain thresholds and other outcomes from a full quantitative sensory testing. We included 124 patients with documented peripheral neuropathic pain. Patients with a steep stimulus-response curve did not overlap with patients with a steep curve on the repetitive pinprick test and both groups more often had decreased rather than increased detection and pain thresholds. Our study questions the concept of hyperpathia and suggests that more studies are needed to identify which symptoms and signs group together and might form a syndrome. Hyperpathia is a syndrome of evoked pain. It is poorly defined and little is known about its clinical presentation. Since it is part of pain symptomatology it is important to have a clear definition and understand the pathophysiology behind. This study explored signs of hyperpathia in a heterogeneous group of patients with peripheral neuropathic pain. We used stimulus-response function and repetitive pinprick stimulation to group patients based on the IASP definition. More studies are needed to understand how symptoms and signs coincide.

Somatosensory alterations after single-unit dental implant immediate loading: A 1-year follow-up study

ObjectiveThis cohort study aimed to assess the incidence of somatosensory alterations after implant surgery using standardized quantitative and qualitative sensory testing. Methods33 participants with single-tooth loss, undergoing immediate implant loading were included. Quantitative Sensory Testing (QST) and Qualitative Sensory Testing (QualST) were conducted at eight time points over a year (baseline to 1 year). Two-Way Repeated Measures ANOVA and post hoc Tukey test were used on QST values and Cochran Q test on QualST. ResultsThe study revealed significant increase in thermal thresholds overtime. At the operated side, overall Cold Pain Threshold (extraoral: p = 0.030; intraoral: p < 0.001), and Cold Detection Threshold (intraoral: p < 0.001) increased overtime. In contralateral region, maxilla Cold Detection Threshold (extraoral: p = 0.024; intraoral: p = 0.031), Warm Detection Threshold (extraoral: p = 0.026; intraoral: p = 0.047) and overall Cold Pain Threshold (extraoral and intraoral: p < 0.001) also increased. QualST showed extraoral pinprick (p = 0.032) and intraoral pinprick (p = 0.000), cold (p = 0.000) and touch (p = 0.002) stimuli abnormalities overtime. ConclusionsSomatosensory alterations after implant surgery were detected in both quantitative and qualitative sensory assessments, but rapidly decreased during the first follow-ups, and then continuously until 1-year. Clinical SignificanceThis study provides clinical and controlled evidence on the real effect of the somatosensory alterations overtime, leading to a better understanding of neurosensory behaviour after single-tooth dental implant rehabilitation.

A Preterm Rat Model for Pain Studies.

This research delves into the consequences of consistent pinprick stimulation on preterm offspring to ascertain its long-term implications for pain sensitivity. The primary objective of this protocol was to investigate the impact of neonatal pinprick stimuli on the pain threshold in the later stages of life using a preterm rat model. By establishing this model, we aim to advance the research on understanding and managing early postnatal pain associated with prematurity. The findings of this study indicate that while the baseline thresholds to mechanical stimuli remained unaffected, there was a notable increase in mechanical hypersensitivity following complete Freund's adjuvant (CFA) injection in adult rats. Interestingly, compared with male rats, female rats demonstrated heightened inflammatory hypersensitivity. Notably, maternal behavior, the weight of the litters, and the growth trajectory of the offspring remained unchanged by the stimulation. The manifestation of altered nociceptive responses in adulthood after neonatal painful stimuli could be indicative of changes in sensory processing and the functioning of glucocorticoid receptors. However, further research is needed to understand the underlying mechanisms involved and to develop interventions for the consequences of prematurity and neonatal pain in adults.

Reliability of quantitative sensory testing in the assessment of somatosensory function after high-frequency stimulation-induced sensitisation of central nociceptive pathways.

The high frequency stimulation (HFS) model can be used alongside quantitative sensory testing (QST) to assess the sensitisation of central nociceptive pathways. However, the validity and between-session reliability of using QST z -score profiles to measure changes in mechanical and thermal afferent pathways in the HFS model are poorly understood. In this study, 32 healthy participants underwent QST before and after HFS (5× 100 Hz trains; 10× electrical detection threshold) in the same heterotopic skin area across 2 repeated sessions. The only mechanical QST z -score profiles that demonstrated a consistent gain of function across repeated test sessions were mechanical pain threshold (MPT) and mechanical pain sensitivity (MPS), which were associated with moderate and good reliability, respectively. There was no relationship between HFS intensity and MPT and MPS z -score profiles. There was no change in low intensity, but a consistent facilitation of high-intensity pin prick stimuli in the mechanical stimulus response function across repeated test sessions. There was no change in cold pain threshold (CPT) and heat pain threshold (HPT) z -score profiles across session 1 and 2, which were associated with moderate and good reliability, respectively. There were inconsistent changes in the sensitivity to innocuous thermal QST parameters, with cool detection threshold (CDT), warm detection threshold (WDT), and thermal sensory limen (TSL) all producing poor reliability. These data suggest that HFS-induced changes in MPS z -score profiles is a reliable way to assess experimentally induced central sensitisation and associated secondary mechanical hyperalgesia in healthy participants.

Generation of a whole-brain hemodynamic response function and sex-specific differences in cerebral processing of mechano-sensation in mice detected by BOLD fMRI.

BOLD fMRI has become a prevalent method to study cerebral sensory processing in rodent disease models, including pain and mechanical hypersensitivity. fMRI data analysis is frequently combined with a general-linear-model (GLM) -based analysis, which uses the convolution of a hemodynamic response function (HRF) with the stimulus paradigm. However, several studies indicated that the HRF differs across species, sexes, brain structures, and experimental factors, including stimulation modalities or anesthesia, and hence might strongly affect the outcome of BOLD analyzes. While considerable work has been done in humans and rats to understand the HRF, much less is known in mice. As a prerequisite to investigate mechano-sensory processing and BOLD fMRI data in male and female mice, we (1) designed a rotating stimulator that allows application of two different mechanical modalities, including innocuous von Frey and noxious pinprick stimuli and (2) determined and statistically compared HRFs across 30 brain structures and experimental conditions, including sex and, stimulus modalities. We found that mechanical stimulation lead to brain-wide BOLD signal changes thereby allowing extraction of HRFs from multiple brain structures. However, we did not find differences in HRFs across all brain structures and experimental conditions. Hence, we computed a whole-brain mouse HRF, which is based on 88 functional scans from 30 mice. A comparison of this mouse-specific HRF with our previously reported rat-derived HRF showed significantly slower kinetics in mice. Finally, we detected pronounced differences in cerebral BOLD activation between male and female mice with mechanical stimulation, thereby exposing divergent processing of noxious and innocuous stimuli in both sexes.

Priming of the autonomic nervous system after an experimental human pain model.

Modulated autonomic responses to noxious stimulation have been reported in experimental and clinical pain. These effects are likely mediated by nociceptive sensitization, but may also, more simply reflect increased stimulus-associated arousal. To disentangle between sensitization- and arousal-mediated effects on autonomic responses to noxious input, we recorded sympathetic skin responses (SSRs) in response to 10 pinprick and heat stimuli before (PRE) and after (POST) an experimental heat pain model to induce secondary hyperalgesia (EXP) and a control model (CTRL) in 20 healthy females. Pinprick and heat stimuli were individually adapted for pain perception (4/10) across all assessments. Heart rate (HR), heart rate variability (HRV) and skin conductance (SCL) were assessed before, during, and after the experimental pain model. Both pinprick- and heat-induced SSRs habituated from PRE to POST in CTRL, but not EXP (p=0.033). Background SCL (during stimuli application) was heightened in EXP compared to CTRL condition during pinprick and heat stimuli (p=0.009). Our findings indicate that enhanced SSRs after an experimental pain model are neither fully related to subjective pain, as SSRs dissociated from perceptual responses, nor to nociceptive sensitization, as SSRs were enhanced after both modalities. Our findings can, however, be explained by priming of the autonomic nervous system during the experimental pain model, which makes the autonomic nervous system more susceptible to noxious input. Taken together, autonomic readouts have the potential to objectively assess not only nociceptive sensitization, but also priming of the autonomic nervous system, which may be involved in the generation of distinct clinical pain phenotypes.

No Evidence That Working Memory Modulates the Plasticity of the Nociceptive System, as Measured by Secondary Mechanical Hypersensitivity

The effect of cognition on the plasticity of the nociceptive system remains controversial. In this study, we examined whether working memory can buffer against the development of secondary hypersensitivity. Thirty-five healthy women participated in 3 experimental conditions. In each condition, they underwent electrical stimulation of the skin for 2 minutes (middle-frequency electrical stimulation [MFS]), which induces secondary hypersensitivity. During MFS, participants executed either an individually tailored and rewarded n-back task (working memory condition), a rewarded reaction-time task (non-working memory condition), or no task at all (control condition). Before and after MFS, participants rated the self-reported intensity and unpleasantness of mechanical pinprick stimuli. Fear of MFS was also assessed. Heart rate variability was measured to examine potential differences between the 3 conditions and steady-state evoked potentials to the electrical stimulation were recorded to investigate differences in cortical responses. We report no significant difference in hypersensitivity between the 3 conditions. Moreover, engaging in the cognitive tasks did not affect the heart rate variability or the steady-state evoked potentials. Interestingly, higher fear of MFS predicted greater hypersensitivity. In conclusion, we found no evidence that working memory affects the plasticity of the nociceptive system, yet pain-related fear plays a role. PerspectiveThis study shows that the execution of a cognitive task, irrespective of cognitive load or working memory, does not significantly modulate the development of secondary hypersensitivity, heart rate variability, or steady-state evoked potentials. However, higher pain-related fear seems to contribute to greater hypersensitivity.

Sympathetic skin response as an objective tool to estimate stimulus-associated arousal in a human model of hyperalgesia

BackgroundPain is a private experience, whose assessment relies on subjective self-reporting. Inaccurate communication renders pain evaluation unreliable in individuals with alteration of consciousness, lack of verbal interaction, cognitive dysfunction or simple malingering, hence the importance of developing reliable objective assessment tools. ObjectivesSince pain is associated with autonomic arousal, here we used readouts of autonomic activity to assess objectively the arousing effect of somatic stimuli in a human model of hyperalgesia. MethodsWe used topical capsaicin to induce cutaneous hypersensitivity in the right arm of 20 healthy volunteers, and recorded sympathetic skin responses (SSR) and numerical perceptive ratings (NRS) to stimulation of the sensitized region and its homologous contralateral site, using brush (Aβ), pinprick (Aδ) and laser (C-Warmth) stimuli. ResultsBoth subjective ratings and SSRs were significantly enhanced to stimulation of the sensitized region, and their respective ratios of maximal enhancement were positively correlated. At individual level, a significant association was observed between SSR and NRS behavior (χ2(1)= 11.03; p < 0.001), with a positive predictive value of 87% (CI95 [77-97%]) for SSR increase predicting enhancement of subjective reports. A “lie experiment” asking subjects to simulate elevated NRS failed to enhance SSRs. Significant habituation of SSRs appeared when stimuli were repeated at ∼15s intervals, hence decreasing their negative predictive value when several consecutive stimuli were averaged (NPV=46%; CI95 [30-62%]). ConclusionThe SSR may represent a rapid and reliable procedure to assess cutaneous hypersensitivity, simple to use in clinical practice and resistant to simulation. Rapid habituation is a drawback that can be countered by using few repetitions and low stimulus rates.

Nociceptive two-point discrimination acuity and body representation failure in polyneuropathy.

Although patients' complaints suggest polyneuropathy (PNP) and neuropathic pain, routine investigations do not always support the diagnosis. Assessing two-point-pain discrimination thresholds (2ptDT) and quantify body representation disturbances might be useful to close this diagnostic gap. Pinprick pain and laser-heat pain perception thresholds and 2ptDT on hands, forearms, lower legs and feet were obtained in 20 PNP patients (mean age: 57.6±13.9) and 20 healthy subjects (mean age: 50.6±4.7years). Body representation disturbances were assessed by self-estimating feet size and the Bath CRPS body perception disturbances questionnaire adapted for PNP. Pain perception thresholds and laser-heat pain 2ptDT were unaltered, but patients had higher pinprick pain 2ptDT then the healthy subjects. The 2ptDT for pinprick at the hands discriminate best between groups (U-test; p=0.001). Furthermore, patients estimated their feet longer than they are. In subsequent multivariate discriminant analyses, 2ptDT for pinprick pain at the hands, 2ptDT for laser-heat pain and the perception thresholds for laser-heat pain at the feet classified 85% of PNP vs. HC correctly. The combination of 2ptDT for pinprick pain at the hands, pinprick pain perception thresholds at the calves and foot length estimation differentiates painful vs. non-painful PNPs correctly in 90% of the cases. Testing 2ptDT for painful pinprick stimuli at the hands and asking for foot length estimation might add to diagnostic accuracy in painful PNP.

Multichanneltranscranial direct current stimulation over the left dorsolateral prefrontalcortex may modulate the induction of secondary hyperalgesia, a double-blinded cross-over study in healthy volunteers.

Central sensitization is thought to play a critical role in the development of chronic pain, and secondary mechanical hyperalgesia is considered one of its hall-mark features. Consequently, interventions capable of modulating its development could have important therapeutic value. Non-invasive neuromodulation of the left dorsolateral prefrontal cortex (DLPFC) has shown potential to reduce pain, both in healthy volunteers and in patients. Whether it can modulate the induction of central sensitization, however, is less well known. To determine whether multifocal transcranial direct current stimulation (tDCS) targeting the left DLPFC affects the development of secondary mechanical hyperalgesia. In this within-subjects, cross-over, double-blinded study, eighteen healthy volunteers participated in three experimental sessions. After 20 minutes of either anodal, cathodal, or sham multichannel tDCS over the left DLPFC, secondary mechanical hyperalgesia was induced using high-frequency electrical stimulation (HFS) of the volar forearm. We assessed intensity of perception to 128 mN mechanical pinprick stimuli at baseline and up to 240 minutes after HFS. We also mapped the area of mechanical hyperalgesia. HFS resulted in a robust and unilateral increase in the intensity of perception to mechanical pinprick stimuli at the HFS arm, which was not different between tDCS stimulation conditions. However, the area of hyperalgesia was reduced after anodal tDCS compared to sham. Anodal tDCS over the left DLPFC modestly modulates the size of the HFS-induced area of secondary mechanical hyperalgesia, suggesting that non-invasive neuromodulation targeting the left DLPFC may be a potential intervention to limit the development of central sensitization.

FV 2 A new neurophysiological test protocol for the assessment of the somatosensory nervous system – from the laboratory to clinical application

During clinical routine diagnostics, the integrity of the somatosensory nervous system is assessed by somatosensory-evoked potentials (SEPs), analyzing Aβ-fiber function, the posterior funiculus, brainstem, and the somatosensory cortex (Muzyka and Estephan 2019). Nevertheless, SEPs cannot provide diagnostic information on small fibers (Cruccu et al. 2004), which form around 80% of the somatosensory nervous system. These small fibers are subdivided into heat-sensitive Aδ-fibers (AMH II), mechanosensitive Aδ-fibers (AMH I), cold-sensitive Aδ-fibers, and C-fibers (mediating noxious and warm stimuli; Gasser 1941). Therefore, a combination of specific tests is required to gain a complete electrophysiological assessment of the somatosensory nervous system or to detect loss of function for specific nerve fiber subtypes. Loss of function of specific subtypes of somatosensory nerve fibers are found in neuropathic disorders, such as polyneuropathy (Bönhof et al. 2017), radiculopathy (Carlstedt 2008; Cavanaugh et al. 1997), traumatic nerve injury (Rotshenker 2011), and others (Gomatos and Rehman 2021). Large-fiber neuropathies only affect thickly myelinated nerve fibers (such as hypocobalaminemia-associated neuropathies; (Franques et al. 2019; Stabler 2013)), while other neuropathic disorders begin by an affection of small fibers (Aδ- and C-fibers), such as chemotherapy-induced polyneuropathy (Timmins et al. 2020). Some neuropathies involve specific subtypes of small nerve fibers, such as a loss of function of cold-mediating Aδ-fibers during the early stage of Fabry‘s disease (Onishi and Dyck 1974). Here, we present a novel neurophysiological test protocol, which assesses a major part of the somatosensory nervous system by recording evoked potentials of touch, pinprick, vibration, heat/heat pain, cold, and warm stimuli. This test protocol was applied on healthy subjects in a first step and then transferred to patients with painful radiculopathy and painful polyneuropathy in a second step. The EP-measurements were compared to clinical data, nerve conduction studies as well as Quantitative Sensory Testing. We found several promising analogies to clinical features of the tested patients, which motivates us and hopefully other researchers to continue on this path with the goal to form a reliable and valid electrophysiological sensory tool that could be used as an outcome measure for future neurophysiological studies and in clinical routine diagnostics.

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

ObjectiveWe aimed to establish an objective neurophysiological test protocol that can be used to assess the somatosensory nervous system. MethodsIn 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. ResultsWe 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 Aβ-fiber-mediated signals and longest within C-fibers. The test protocol detected function loss within the Aβ-fiber and Aδ-fiber-range in PNP patients. This function loss corresponded with QST findings. ConclusionIn 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. SignificanceEstablished and custom-made stimulators were combined to assess different fiber subtypes of the somatosensory nervous system using modality-specific evoked potentials.

Perceptual correlates of homosynaptic long-term potentiation in human nociceptive pathways: a replication study.

Animal studies have shown that high-frequency stimulation (HFS) of peripheral C-fibres induces long-term potentiation (LTP) within spinal nociceptive pathways. The aim of this replication study was to assess if a perceptual correlate of LTP can be observed in humans. In 20 healthy volunteers, we applied HFS to the left or right volar forearm. Before and after applying HFS, we delivered single electrical test stimuli through the HFS electrode while a second electrode at the contra-lateral arm served as a control condition. Moreover, to test the efficacy of the HFS protocol, we quantified changes in mechanical pinprick sensitivity before and after HFS of the skin surrounding both electrodes. The perceived intensity was collected for both electrical and mechanical stimuli. After HFS, the perceived pain intensity elicited by the mechanical pinprick stimuli applied on the skin surrounding the HFS-treated site was significantly higher compared to control site (heterotopic effect). Furthermore, we found a higher perceived pain intensity for single electrical stimuli delivered to the HFS-treated site compared to the control site (homotopic effect). Whether the homotopic effect reflects a perceptual correlate of homosynaptic LTP remains to be elucidated.

Pancreatic QST Differentiates Chronic Pancreatitis Patients into Distinct Pain Phenotypes Independent of Psychiatric Comorbidities

Quantitative sensory testing (QST) has been previously used to study pain in chronic pancreatitis (CP) but included methods that are not suitable for clinical purposes. The aims of this study were to determine if pancreatic QST (P-QST) can differentiate patients into distinct pain phenotypes and to determine the association of these with their clinical pain and psychiatric comorbidities. A multicenter cross-sectional study was conducted where patients completed validated questionnaires assessing quality of life (QoL), depression and anxiety scores as well as clinical pain symptoms followed by P-QST which included a cold pressor test, repetitive pinprick stimuli and pressure stimulation of the upper abdominal (T10) and control dermatomes. P-QST categorized patients into pain phenotypes based on a previously established nomogram. QoL, clinical pain and psychiatric assessment scores were compared across these groups. A total of 179 patients were enrolled with a mean age of 54.1±13.6 years among whom 59% were males and 42% had an alcoholic etiology. P-QST showed no hyperalgesia in 91 (51%), segmental hyperalgesia in 50 (28%) and widespread hyperalgesia in 38 (21%) patients. Patients with widespread hyperalgesia had significantly higher pain intensity scores (P= .03) and rates of constant pain (P= .002) as well as decreased QoL (P < .001) and physical functioning (P=.03) in comparison with the other two pain phenotypes. In contrast, psychiatric comorbidities were similar across all groups. P-QST may serve as a novel unbiased pain assessment tool in CP as it categorizes patients into distinct pain phenotypes independent of their psychiatric comorbidities.

Assessment of somatosensory changes in Chinese temporomandibular disorders arthralgia patients by quantitative sensory testing.

Somatosensory changes in Chinese temporomandibular disorders (TMD) arthralgia patients have not been fully studied by the latest technologies. This study aims at assessing somatosensory changes in Chinese TMD arthralgia patients quantitatively. Standardised quantitative sensory testing (QST) was performed on the pain sites and contralateral sites of 40 patients diagnosed with TMD arthralgia according to the Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) before and after medication; similar measures were taken in 40 age- and gender-matched healthy controls. Differences within and between groups were assessed through Z-scores, two-way ANOVA and loss/gain coding system. The pain sites of patients presented increased sensitivity to thermal stimuli and mechanical pain stimuli together with decreased sensitivity to mechanical tactile stimuli before medication (P<.001). Before treatment, 100% of patients had somatosensory abnormalities at the pain sites; the most frequent abnormalities were somatosensory gain to cold nociceptive, pinprick and pressure stimuli, and the most frequent loss/gain score was L0G3 (no somatosensory loss with a gain of thermal and mechanical somatosensory function; 70.0%). After treatment, although the clinical symptoms and signs of 40 patients disappeared, 80.0% of the patients' pain sites still showed multiple phenotype abnormalities. The most frequent loss/gain score was L0G2 (no somatosensory loss with a gain of mechanical somatosensory function; 35.0%). Multiple phenotypes of facial somatosensory abnormalities were detected in Chinese TMD arthralgia patients before and after treatment, despite the disappearance of clinical signs and symptoms. Individual variations indicate a possible need for subgroup classification, individualised management and mechanism-based treatment.

Central sensitization of nociceptive pathways demonstrated by robot-controlled pinprick-evoked brain potentials

ObjectiveThe aim of this study was to assess the effect of central sensitization, induced by high frequency electrical stimulation of the skin (HFS), on pinprick-evoked brain potentials (PEPs) using robot-controlled mechanical pinprick stimulation and a stimulus evaluation task. MethodsIn 16 healthy volunteers HFS was applied to the right volar forearm. Robot- controlled pinprick stimuli (64 mN) were applied before and 20 minutes after HFS to the skin surrounding the area onto which HFS was applied. During pinprick stimulation, the EEG was recorded and the quality of perception and perceived intensity of the pinprick stimuli was collected. ResultsAfter HFS, the skin surrounding the site at which HFS was delivered showed increased mechanical pinprick sensitivity. Both the early-latency negative peak of PEPs and the later-latency peak were significantly increased after HFS. ConclusionsThis study shows increased PEPs after HFS when they are elicited by a robot-controlled mechanical pinprick stimulator and participants are engaged in a stimulus evaluation task during pinprick stimulation. SignificanceThis is the first study that shows a significant increase of both PEP peaks, and therefore, it provides a preferred setup for assessing the function of mechanical nociceptive pathways in the context of central sensitization.

Within- and between-session reliability of secondary hyperalgesia induced by electrical high-frequency stimulation.

An increasing number of studies are focusing on secondary hyperalgesia to better understand central sensitization, as this phenomenon may play an important role in persistent pain. Recent studies have shown that, compared to the classical high-frequency stimulation protocol (HFS) at 100Hz, a protocol using 42Hz stimulation induces a more intense and a larger area of secondary hyperalgesia (SH). The aim of this study was to investigate the within- and between-session reliability of SH induced by this optimized HFS protocol. Thirty-two healthy subjects received HFS to their volar forearm in two sessions, separated by at least 2weeks. SH was assessed by measuring the area size of increased sensitivity to pinprick stimuli after applying HFS, the sensitivity to pinprick stimuli after applying HFS and the change in pinprick sensitivity after versus before HFS. Assessments were made before HFS, and 30, 35 and 40min after HFS. Relative and absolute reliability were analysed using intraclass correlation coefficients (ICCs), coefficients of variation (CVs), standard error of means (SEMs) and the minimum detectable changes (MDCs). The area of SH showed good to excellent within-session and between-session relative reliability (ICCs>0.80), except for the change in pinprick sensitivity, which showed close to poor between-session relative reliability (ICC=0.53). Furthermore, measures of absolute reliability generally demonstrated large between-subject variability and significant fluctuations across repeated measurements. HFS-induced hyperalgesia is suitable to discriminate or compare individuals but it may not be sensitive to changes due to an intervention. It is crucial to evaluate central sensitization adequately in humans. This study formally establishes the reliability of secondary hyperalgesia induced by electrical high-frequency stimulation. The results of this study will improve future studies investigating secondary hyperalgesia in humans.

Orofacial quantitative sensory testing: Current evidence and future perspectives.

Background and objectiveOrofacial quantitative sensory testing (QST) is an increasingly valuable psychophysical tool for evaluating neurosensory disorders of the orofacial region. Here, we aimed to evaluate the current evidence regarding this testing method and to discuss its future clinical potential.Data treatmentWe conducted a literature search in Medline, Embase and Scopus for English‐language articles published between 1990 and 2019. The utilized search terms included QST, quantitative, sensory testing and neurosensory, which were combined using the AND operator with the terms facial, orofacial, trigeminal, intraoral and oral.ResultsOur findings highlighted many methods for conducting QST—including method of levels, method of limits and mapping. Potential stimuli also vary, and can include mechanical or thermal stimulation, vibration or pinprick stimuli. Orofacial QST may be helpful in revealing disease pathways and can be used for patient stratification to validate the use of neurosensory profile‐specific treatment options. QST is reportedly reliable in longitudinal studies and is thus a candidate for measuring changes over time. One disadvantage of QST is the substantial time required; however, further methodological refinements and the combination of partial aspects of the full QST battery with other tests and imaging methods should result in improvement.ConclusionsOverall, orofacial QST is a reliable testing method for diagnosing pathological neurosensory conditions and assessing normal neurosensory function. Despite the remaining challenges that hinder the use of QST for everyday clinical decisions and clinical trials, we expect that future improvements will allow its implementation in routine practice.