Thermal Sensory Thresholds Research Articles

Effect of Lingual Nerve Block and Localised Somatosensory Abnormalities in Patients With Burning Mouth Syndrome-A Randomised Crossover Double-Blind Trial.

To investigate the effect of a lingual nerve block on spontaneous pain in patients with burning mouth syndrome (BMS) and to estimate associated somatosensory abnormalities by quantitative sensory testing (QST). A standardised QST battery including cold detection threshold (CDT), warmth detection threshold (WDT), thermal sensory limen (TSL), paradoxical heat sensation (PHS), cold pain threshold (CPT), heat pain threshold (HPT), mechanical pain threshold (MPT), wind-up ratio (WUR) and pressure pain threshold (PPT) was performed at the oral mucosa of the most painful site and intraoral control site in 20 BMS patients, and at the tongue and cheek mucosa in 22 age- and gender-matched healthy controls. The effect of a lingual nerve block on spontaneous burning pain reported by the BMS patients on a 0-10 cm visual analogue scale (VAS) was investigated in a randomised double-blind crossover design using (1 mL) lidocaine (lido) or saline (sal) with an interval of 1 week. The BMS patients were grouped into 'central' and 'peripheral' mechanisms based on the effect of the lingual nerve injections. For each BMS patient, Z-scores and Loss/Gain scores were computed. Differences among groups and sites were analysed using a two-way ANOVA. Differences within group were assessed by paired t-test. The 20 BMS patients were characterised on the basis of VAS changes (ΔLido-ΔSal) as a peripheral BMS subgroup (n = 9) with pain relief more than 1 cm on the VAS and a central BMS subgroup (n = 11) with pain relief less than 1 cm. BMS patients (n = 20) had lower sensitivity to thermal stimuli (i.e., CDT, WDT, TSL, CPT, HPT and PPT) and higher sensitivity to mechanical stimuli (i.e., PPT) compared with controls (p ≤ 0.007). Based on Loss/Gain coding, L1G0 (loss of thermal somatosensory function with no somatosensory gain, 55.0%) was the most frequent coding in the BMS group, which was higher than 11.4% in the control group (p < 0.001). Surprisingly, there was no significant difference between the peripheral and central BMS subgroups with regard to the Z-scores of any of the nine QST parameters (p > 0.097). The results of the lingual nerve blocks demonstrated two distinct phenotypes with either peripheral or central mechanisms but no direct impact on somatosensory function. Overall, somatosensory function in BMS patients seems abnormal in the painful areas compared to matched controls with a conspicuous loss of thermosensory function.

Effect of repeated topical capsaicin gel administration on oral thermal quantitative sensory testing: A two-arm longitudinal study.

Few studies used thermal quantitative sensory testing to assess the effects of repeated capsaicin gel administration in the oral cavity. This study aimed to investigate thermal sensory and pain thresholds before and after repeated capsaicin gel administration. Ten healthy females (22 ± 2 years) applied a capsaicin gel on the gingival mucosa twice daily for 14 days, and heat pain threshold, warm detection threshold, cold pain threshold, and cold detection threshold were assessed on the oral mucosa. Measurements were performed before and after the 14 days and were compared to a control sample (n = 10, all females, 23 ± 3 years). Capsaicin increased heat pain threshold in the anterior maxilla by 2.9°C (95% CI: 1.6-4.2) (p < 0.001) and in the anterior mandible by 2.2°C (95% CI: 1.0-3.4) (p = 0.001), similar to warm detection threshold that increased by Δ1.1°C (95% CI: 0.3-1.9) (p = 0.009). No significant changes were found in the controls. These findings encourage the use of thermal quantitative sensory testing in the oral cavity to assess thermal sensation, which might be useful for assessing the effects of therapies aimed at reducing pain.

Visual psychosocial profiling of Chinese temporomandibular disorder pain patients and correlations with somatosensory function.

Psychosocial function of Chinese temporomandibular disorders (TMD) pain patients and the correlation with somatosensory function has not been sufficiently studied. The study aims at assessing the psychosocial function of Chinese TMD pain patients by visualisation method and evaluating the correlations with somatosensory function quantitatively. The Symptom Checklist 90 (SCL-90) questionnaire and standardised quantitative sensory testing (QST) were administered to 70 Chinese TMD pain patients and age- and gender-matched healthy controls (HCs). Of these, 40 TMD arthralgia patients received QST before and after medication. Psychosocial and somatosensory parameters were transformed into standardised scores. Differences within groups were assessed through t tests. Correlations between psychosocial and somatosensory profiles were explored through correlation analyses with Bonferroni correction for multiple comparisons. 100% of the Chinese TMD pain patients exhibited psychosocial distress in contrast to HCs. Anger and hostility showed negative correlation with the thermal nonnociceptive parameter (thermal sensory limen, p =.002) and nociceptive parameters (cold pain threshold and pain pressure threshold, p<.001). Correlation analysis indicated that cold detection threshold was negatively correlated with somatization and mechanical pain sensitivity had a negative correlation with anger and hostility through medical treatment (p <.001). Visual psychosocial profiles provided an easy overview of psychosocial function in Chinese TMD pain patients. Anger and hostility was associated with increased thermal nonnociceptive and nociceptive sensitivity to stimuli. Psychosocial distress might be negatively associated with TMD treatment response which indicated a possible need for psychological intervention during treatment.

Distinguishing fibromyalgia syndrome from small fiber neuropathy: a clinical guide.

Fibromyalgia syndrome (FMS) and small fiber neuropathy (SFN) are distinct pain conditions that share commonalities and may be challenging as for differential diagnosis. To comprehensively investigate clinical characteristics of women with FMS and SFN to determine clinically applicable parameters for differentiation. We retrospectively analyzed medical records of 158 women with FMS and 53 with SFN focusing on pain-specific medical and family history, accompanying symptoms, additional diseases, and treatment. We investigated data obtained using standardized pain, depression, and anxiety questionnaires. We further analyzed test results and findings obtained in standardized small fiber tests. FMS patients were on average ten years younger at symptom onset, described higher pain intensities requiring frequent change of pharmaceutics, and reported generalized pain compared to SFN. Pain in FMS was accompanied by irritable bowel or sleep disturbances, and in SFN by paresthesias, numbness, and impaired glucose metabolism (P < 0.01 each). Family history was informative for chronic pain and affective disorders in FMS (P < 0.001) and for neurological disorders in SFN patients (P < 0.001). Small fiber pathology in terms of skin denervation and/or thermal sensory threshold elevation was present in 110/158 (69.7 %) FMS patients and 39/53 (73.6 %) SFN patients. FMS patients mainly showed proximally reduced skin innervation and higher corneal nerve branch densities (p<0.001) whereas SFN patients were characterized by reduced cold detection and prolonged electrical A-delta conduction latencies (P < 0.05). Our data show that FMS and SFN differ substantially. Detailed pain, drug and family history, investigating blood glucose metabolism, and applying differential small fiber tests may help to improve diagnostic differentiation and targeted therapy.

The thermal sensation threshold and its reliability induced by the exposure to 28 GHz millimeter-wave.

The application of 28 GHz millimeter-wave is prevalent owing to the global spread of fifth-generation wireless communication systems. Its thermal effect is a dominant factor which potentially causes pain and tissue damage to the body parts exposed to the millimeter waves. However, the threshold of this thermal sensation, that is, the degree of change in skin temperature from the baseline at which the first subjective response to the thermal effects of the millimeter waves occurs, remains unclear. Here, we investigated the thermal sensation threshold and assessed its reliability when exposed to millimeter waves. Twenty healthy adults were exposed to 28 GHz millimeter-wave on their left middle fingertip at five levels of antenna input power: 0.2, 1.1, 1.6, 2.1, and 3.4 W (incident power density: 27-399 mW/cm2). This measurement session was repeated twice on the same day to evaluate the threshold reliability. The intraclass correlation coefficient (ICC) and Bland-Altman analysis were used as proxies for the relative and absolute reliability, respectively. The number of participants who perceived a sensation during the two sessions at each exposure level was also counted as the perception rate. Mean thermal sensation thresholds were within 0.9°C-1.0°C for the 126-399 mW/cm2 conditions, while that was 0.2°C for the 27 mW/cm2 condition. The ICCs for the threshold at 27 and 126 mW/cm2 were interpreted as poor and fair, respectively, while those at higher exposure levels were moderate to substantial. Apart from a proportional bias in the 191 mW/cm2 condition, there was no fixed bias. All participants perceived a thermal sensation at 399 mW/cm2 in both sessions, and the perception rate gradually decreased with lower exposure levels. Importantly, two-thirds of the participants answered that they felt a thermal sensation in both or one of the sessions at 27 mW/cm2, despite the low-temperature increase. These results suggest that the thermal sensation threshold is around 1.0°C, consistent across exposure levels, while its reliability increases with higher exposure levels. Furthermore, the perception of thermal sensation may be inherently ambiguous owing to the nature of human perception.

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.

Comparison of Cerebral Blood Volume during Cold and Warm Stimulation in Elderly and Young Subjects.

Dementia involves a neuronal loss in the primary somatosensory cortex of the parietal lobe, causing dementia patients to perceive pain stimuli hardly. The function of temperature sensation declines. Studies measuring brain blood volume using near-infrared light have reported that patients suffering from dementia have less activation than healthy elderly people. However, the majority of these studies used tests related to cognitive function and the frontal lobe, and few have examined thermal sensation. The present study aimed to investigate the effect of cold and warm stimulation on cerebral blood volume in elderly and young subjects. This observational study measured changes in oxygenated hemoglobin concentrations in the frontal cortex during cold and warm stimulation in elderly and young subjects using a near-infrared light device. The mean and standard deviation of the change in oxygenated hemoglobin concentration before and after cold and warm stimulation, as well as the center-of-gravity values, were compared between the young and the elderly. During warm stimulation, the younger subjects showed an increase in blood oxygenated hemoglobin levels; however, the difference was not significant. For the elderly, no change was observed during the task. The center of gravity values was lower in the young compared to the elderly which was similar to the reaction threshold. No significant changes were observed during cold stimulation. Thermal sensation thresholds were impaired in the elderly compared to the young; however, cerebral blood volume changes were unclear.

It is one or the other: No overlap between healthy individuals perceiving thermal grill illusion or paradoxical heat sensation

Paradoxical heat sensation (PHS) and the thermal grill illusion (TGI) are both related to the perception of warmth or heat from innocuous cold stimuli. Despite being described as similar perceptual phenomena, recent findings suggested that PHS is common in neuropathy and related to sensory loss, while TGI is more frequently observed in healthy individuals. To clarify the relationship between these two phenomena, we conducted a study in a cohort of healthy individuals to investigate the association between PHS and TGI.We examined the somatosensory profiles of 60 healthy participants (34 females, median age 25 years) using the quantitative sensory testing (QST) protocol from the German Research Network on Neuropathic Pain. The number of PHS was measured using a modified thermal sensory limen (TSL) procedure where the skin was transiently pre-warmed, or pre-cooled before the PHS measure. This procedure also included a control condition with a pre-temperature of 32 °C. The number of TGI responses was quantified during simultaneous application of warm and cold innocuous stimuli. All participants had normal thermal and mechanical thresholds compared to the reference values from the QST protocol. Only two participants experienced PHS during the QST procedure. In the modified TSL procedure, we found no statistically significant differences in the number of participants reporting PHS in the control condition (N = 6) vs. pre-warming (N = 3; min = 35.7 °C, max = 43.5 °C) and pre-cooling (N = 4, min = 15.0 °C, max = 28.8 °C) conditions. Fourteen participants experienced TGI, and only one participant reported both TGI and PHS. Individuals with TGI had normal or even increased thermal sensation compared to individuals without TGI.Our findings demonstrate a clear distinction between individuals experiencing PHS or TGI, as there was no overlap observed when using identical warm and cold temperatures that were alternated either temporally or spatially. While PHS was previously related to sensory loss, our study revealed that TGI is associated with normal thermal sensitivity. This suggests that an efficient thermal sensory function is essential in generating the illusory sensation of pain of the TGI.

Endoscopic visualization of the inferior alveolar nerve associated with somatosensory changes after impacted mandibular third molar extraction.

The aim of this study is to assess the relationship between somatosensory functional changes and inferior alveolar nerve (IAN) exposure after impacted mandibular third molars (M3M) removal. We recruited 35 patients who underwent impacted M3M extraction near the IAN. The M3Ms were extracted by combined endoscopy, piezosurgery, and contra-angle high-speed turbine handpiece. All IAN canal perforations and exposed regions were recorded and measured by endoscopy after extraction and on cone-beam computed tomography (CBCT) images before extraction. The patients were followed up 1, 7, and 35days after surgery. A standardized quantitative sensory testing (QST) battery was performed on the lower lip skin. All of 35 cases had exposed IAN on CBCT images, 5 of which had no exposed IAN under endoscopy. For the other 30 cases, the endoscopy-measured IAN length and width were shorter than the CBCT measurements (P < 0.001). The warm and mechanical detection thresholds (MDT) on the operation side were significantly higher than the contralateral side after surgery (P < 0.05). Thermal sensory limen, MDT, and cold pain threshold were strongly correlated with the exposed IAN length and MDT also with the exposed IAN width one day after surgery. In conclusion, it was found that not all exposed IAN in CBCT images were real exposure after surgery. The intraoperative exposed IAN endoscopic measurements were smaller than by CBCT and strongly correlated with some QST parameters.

Neuromodulation Therapy for Chemotherapy-Induced Peripheral Neuropathy: A Systematic Review.

Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating and painful condition in patients who have received chemotherapy. The role of neuromodulation therapy in treating pain and improving neurological function in CIPN remains unclear and warrants evidence appraisal. In compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we performed a systematic review to assess change in pain intensity and neurological function after implementation of any neuromodulation intervention for CIPN. Neuromodulation interventions consisted of dorsal column spinal cord stimulation (SCS), dorsal root ganglion stimulation (DRG-S), or peripheral nerve stimulation (PNS). In total, 15 studies utilized SCS (16 participants), 7 studies utilized DRG-S (7 participants), and 1 study utilized PNS (50 participants). Per the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) criteria, there was very low-quality GRADE evidence supporting that dorsal column SCS, DRG-S, and PNS are associated with a reduction in pain severity from CIPN. Results on changes in neurological function remained equivocal due to mixed study findings on thermal sensory thresholds and touch sensation or discrimination. Future prospective, well-powered, and comparative studies assessing neuromodulation for CIPN are warranted.

When cooling of the skin is perceived as warmth: Enhanced paradoxical heat sensation by pre-cooling of the skin in healthy individuals

ABSTRACT A paradoxical heat sensation (PHS) is the misperception of warmth when the skin is cooled. PHS is uncommon in healthy individuals but common in patients with neuropathy and is associated with reduced thermal sensitivity. Identifying conditions that contribute to PHS may indirectly help us understand why some patients experience PHS. We hypothesized that pre-warming increased the number of PHS and that pre-cooling had minimal effect on PHS. We tested 100 healthy participants’ thermal sensitivity on the dorsum of their feet by measuring detection and pain thresholds to cold and warm stimuli and PHS. PHS was measured using the thermal sensory limen (TSL) procedure from the quantitative sensory testing protocol of the German Research Network on Neuropathic Pain and by using a modified TSL protocol (mTSL). In the mTSL we examined the participants’ thermal detection and PHS after pre-warming of 38°C and 44°C and pre-cooling of 26°C and 20°C. Compared to a baseline condition, the number of PHS responders was significantly increased after pre-cooling (20°C: RR = 1.9 (1.1; 3.3), p = 0.023 and 26°C: RR = 1.9 (1.2; 3.2), p = 0.017), but not significantly after pre-warming (38°C: RR = 1.5 (0.86; 2.8), p = 0.21 and 44°C: RR = 1.7 (.995; 2.9), p = 0.078). Pre-warming and pre-cooling increased the detection threshold of both cold and warm temperatures. We discussed these findings in relation to thermal sensory mechanisms and possible PHS mechanisms. In conclusion, PHS and thermosensation are closely related and pre-cooling can induce PHS responses in healthy individuals.

Assessment of Sensory Thresholds in Dogs using Mechanical and Hot Thermal Quantitative Sensory Testing.

Quantitative sensory testing (QST) is used to evaluate the function of the somatosensory system in dogs by assessing the response to applied mechanical and thermal stimuli. QST is used to determine normal dogs' sensory thresholds and evaluate alterations in peripheral and central sensory pathways caused by various disease states, including osteoarthritis, spinal cord injury, and cranial cruciate ligament rupture. Mechanical sensory thresholds are measured by electronic von Frey anesthesiometers and pressure algometers. They are determined as the force at which the dog exhibits a response indicating conscious stimulus perception. Hot thermal sensory thresholds are the latency to respond to a fixed or ramped temperature stimulus applied by a contact thermode. Following a consistent protocol for performing QST and paying attention to details of the testing environment, procedure, and individual study subjects are critical for obtaining accurate QST results for dogs. Protocols for the standardized collection of QST data in dogs have not been described in detail. QST should be performed in a quiet, distraction-free environment that is comfortable for the dog, the QST operator, and the handler. Ensuring that the dog is calm, relaxed, and properly positioned for each measurement helps produce reliable, consistent responses to the stimuli and makes the testing process more manageable. The QST operator and handler should be familiar and comfortable with handling dogs and interpreting dogs' behavioral responses to potentially painful stimuli to determine the endpoint of testing, reduce stress, and maintain safety during the testing process.

Sensory Function and Psychological Factors in Children With Complex Regional Pain Syndrome Type 1.

Objective:To assess thermal-sensory thresholds and psychosocial factors in children with Complex Regional Pain Syndrome Type 1 (CRPS-I) compared to healthy children.Methods:We conducted quantitative sensory testing on 34 children with CRPS-I and 56 pain-free children. Warm, cool, heat, and cold stimuli were applied to the forearm. Children with CRPS-I had the protocol administered to the pain site and the contralateral-pain site. Participants completed the self-report Behavior Assessment System for Children.Results:Longer pain durations (>5.1 months) were associated with decreased sensitivity to cold pain on the pain site (P = .04). Higher pain-intensity ratings were associated with elevated anxiety scores (P = .03). Anxiety and social stress were associated with warmth sensitivity (both P < .05) on the contralateral-pain site.Conclusions:Pain duration is an important factor in assessing pediatric CRPS-I. Hyposensitivity in the affected limb may emerge due to degeneration of nociceptive nerves. Anxiety may contribute to thermal-sensory perception in childhood CRPS-I.

Previous recreational cold exposure does not alter endothelial function or sensory thermal thresholds in the hands or feet.

What is the central question of this study? Does recreational cold exposure result in cold sensitivity and is this associated with endothelial dysfunction and impaired sensory thermal thresholds? What is the main finding and its importance? Previous cold exposure was correlated with cold sensitivity of the foot, which might indicate the development of a subclinical non-freezing cold injury. Endothelial function and thermal detection were not impaired in cold-sensitive individuals; therefore, further research is required to understand the pathophysiology of subclinical and clinical forms of non-freezing cold injury. In this study, we investigated whether cold-sensitive (CS) individuals, who rewarm more slowly after a mild cold challenge, have impaired endothelial function and sensory thermal thresholds (STTs) and whether this is related to reported cold exposure. Twenty-seven participants with varying previous cold exposure undertook three tests: an STT test, i.e. determination of warm and cold STTs of the fingers and dorsal foot; an endothelial function test, i.e. measurement of cutaneous vascular conductance (CVC) during iontophoresis of ACh on the forearm, finger and foot; and a CS test, involving immersion of a foot for 2min in water at 15°C followed by 10min of rewarming in air at 30°C. Toe skin temperature (Tsk ) measured during the CS test was used to form a CS group (<32°C before and 5min after immersion) and an otherwise closely matched control group [Tsk >32°C; n=9 (four women) for both groups]. A moderate relationship was found between cold exposure ranking and Tsk rewarming (r=0.408, P=0.035, n=27) but not STT or endothelial function. The Tsk and blood flow were lower in CS compared with control subjects before and after foot immersion [Tsk , mean (SD): 30.3(0.9) versus 34.8(0.8) and 27.9(0.8) versus 34.3(0.8)°C, P<0.001; and CVC: 1.08(0.79) versus 3.82(1.21) and 0.79(0.52) versus 3.45(1.07)fluxmmHg-1 , n=9, P<0.001, respectively]. However, no physiologically significant differences were observed between groups for endothelial function or STT. A moderate correlation between previous cold exposure and toe Tsk rewarming after foot immersion was observed; however, CS was not associated with impaired endothelial function or reduced thermal detection.

Long-term small-fiber neuropathy and pain sensitization in survivors of pediatric acute lymphoblastic leukemia after stem cell transplantation

PurposeWe aimed at describing for the first time peripheral small-fiber neurotoxicity and pain sensitization in survivors of pediatric acute lymphoblastic leukemia after stem cell transplantation (SCT).MethodsIn a cross-sectional, retrospective, single-center study, we assessed 25 relapse-free long-term survivors (median age at SCT: 11 ± 4.9 years; median time between SCT and testing: 8.25 years, 19 males) using a reduced version of the pediatric-modified total neuropathy score for clinical assessment and Quantitative Sensory Testing (QST). Inclusion criteria: ge 6 years old at testing, le 18 years old at time of SCT, ge 1 year between SCT and testing.ResultsNine patients (36%) had peripheral neuropathy as defined by the clinical red-pmTNS (≥ 4). The QST parameters mechanical pain sensitivity, mechanical detection threshold, thermal sensory limen, vibration detection threshold and pressure pain threshold were significantly abnormal in the survivor cohort (p < 0.0038). Except for one, all survivors showed at least one abnormal QST parameter. When using QST, signs of small and large fiber dysfunction were present in 22 (88%) and 17 (68%) survivors, respectively. More than half of all survivors were found to experience pathologic sensitization to pain.Conclusions and implications for cancer survivorsSurvivors of pediatric acute lymphoblastic leukemia after SCT are at high risk for long-term peripheral neuropathy with a dominating small-fiber and pain sensitization pattern.

The Effect of Granisetron on Sensory Detection and Pain Thresholds in Facial Skin of Healthy Young Males.

Background: The specific serotonin type 3 (5-HT3)-receptor antagonist granisetron effectively reduces clinical as well as experimental muscle pain and hyperalgesia and with a duration that exceeds that of lidocaine. Hence, it may be an alternative to lidocaine as a local anesthetic. There are also some indications that granisetron in addition to 5-HT3 receptors blocks sodium channels. Thus, the local anesthetic effect by granisetron may resemble that of lidocaine, but this has not been tested. The aim of this study was therefore to compare the effect granisetron has on facial skin sensitivity to the effect of lidocaine and isotonic saline.Methods: This was a randomized, controlled, and double-blind study, in which 1 ml of either granisetron (test-substance), lidocaine (positive control), or isotonic saline (negative control) was injected into the skin over the masseter muscle at three different occasions in 18 healthy males (27.2 ± 5.8 years old). Skin detection thresholds and pain thresholds for thermal stimuli as well as mechanical detection thresholds and sensitivity to a painful mechanical (pinprick) stimulus were assessed before (baseline) and 5, 20, 40, and 60 min after injection. The quality and area of subjective sensory change over the cheek were assessed 20 min after injection.Results: All substances increased the mechanical detection threshold (granisetron: p = 0.011; lidocaine: p = 0.016; saline: p = 0.031). Both granisetron and lidocaine, but not isotonic saline, increased the heat detection thresholds (p < 0.001 and p < 0.02, respectively), but not the cold detection thresholds. Granisetron and lidocaine also reduced pinprick pain (p = 0.001 for each comparison). There were no significant differences between granisetron and lidocaine for any of these variables. There was no effect on thermal pain thresholds for any substance.Conclusion: The similar analgesic patterns on mechanical sensory and pain thresholds as well as thermal sensory thresholds over the facial skin by subcutaneous injection of granisetron and lidocaine shown in this study and the absence of paresthesia, in combination with the reduced pain intensity and pressure pain sensitivity shown in previous studies, indicate that granisetron might be a novel candidate as a local anesthetic.

Effects of external low intensity focused ultrasound on electrophysiological changes in vivo in a rodent model of common peroneal nerve injury

Non-invasive treatment methods for neuropathic pain are lacking. We assess how modulatory low intensity focused ultrasound (liFUS) at the L5 dorsal root ganglion (DRG) affects behavioral responses and sensory nerve action potentials (SNAPs) in a common peroneal nerve injury (CPNI) model. Rats were assessed for mechanical and thermal responses using Von Frey filaments (VFF) and the hot plate test (HPT) following CPNI surgery. Testing was repeated 24 h after liFUS treatment. Significant increases in mechanical and thermal sensory thresholds were seen post-liFUS treatment, indicating a reduction in sensitivity to pain (p < 0.0001, p = 0.02, respectively). Animals who received CPNI surgery had significant increases in SNAP latencies compared to sham CPNI surgery animals (p = 0.0003) before liFUS treatment. LiFUS induced significant reductions in SNAP latency in both CPNI liFUS and sham CPNI liFUS cohorts, for up to 35 min post treatment. No changes were seen in SNAP amplitude and there was no evidence of neuronal degeneration 24 h after liFUS treatment, showing that liFUS did not damage the tissue being modulated. This is the first in vivo study of the impact of liFUS on peripheral nerve electrophysiology in a model of chronic pain. This study demonstrates the effects of liFUS on peripheral nerve electrophysiology in vivo. We found that external liFUS treatment results in transient decreased latency in common peroneal nerve (CPN) sensory nerve action potentials (SNAPs) with no change in signal amplitude.

Quantitative sensory testing predicts histological small fiber neuropathy in postural tachycardia syndrome.

Retrospective investigation of the somatosensory profile and prediction of histologic small fiber neuropathy (SFN) in postural orthostatic tachycardia syndrome (POTS) was performed using quantitative sensory testing (QST) as a standardized noninvasive test. In this investigation, full data sets from 30 patients (age: 34.03 ± 10.82 years, n = 6 males), including results of autonomic function testing, norepinephrine values, skin biopsy, and QST, were retrospectively analyzed. The QST data were compared with healthy controls (HCs) (age: 34.20 ± 10.5 years, n = 6 males, t test: 0.95). The evaluation of all QST parameters in POTS compared with HCs yielded differences in all thermal parameters (cold detection threshold: p < 0.05, warm detection threshold: p < 0.001, thermal sensory limen: p < 0.001, cold pain threshold: p < 0.05, and heat pain threshold: p < 0.001) and in paradoxical heat sensations (p < 0.05). Differences in nonpainful stimuli (mechanical detection threshold: p < 0.05 and vibration detection threshold: p < 0.001) were also detected. All patients who had clinical signs of SFN in combination with impairment of small fibers in QST also had SFN on skin biopsy. These results suggest that a non-region-specific SFN in POTS compared with controls can be detected by noninvasive QST that predicts histologic small fiber pathology.

The Association Between Phosphorylated Neurofilament Heavy Chain (pNF-H) and Small Fiber Neuropathy (SFN) in Patients with Impaired Glucose Tolerance.

IntroductionSmall fiber neuropathy (SFN)—the early stage of diabetic peripheral neuropathy (DPN)—progresses gradually and is difficult to diagnose using neurophysiological tests. To facilitate the early diagnosis of SFN, biomarkers for SFN must be identified. The purpose of this study was to investigate the characteristics of SFN in prediabetic patients and the relationship between pNF-H and SFN.Methods44 IGT patients (inpatients and outpatients) were selected at random. 33 healthy subjects served as controls. Data on clinical characteristics and laboratory parameters were collected. Quantitative sensory testing (QST), electromyography (EMG), and Sudoscan were performed, and pNF-H was measured by ELISA.Results24 of the 44 patients with impaired glucose tolerance (IGT) were diagnosed with SFN according to the modified Toronto Diabetic Neuropathy Expert Group consensus criteria. The thermal sensory thresholds of the IGT-SFN group were significantly different from those of the CTRL group (p < 0.05), except for the heat pain threshold. The sensory nerve action potential (SNAP) of the sural nerve was 12.39 in the IGT-SFN group, which was significantly lower than those in the other groups. No significant difference in nerve conduction velocity (NCV) was observed among the three groups. The electrochemical skin conductance (ESC) in the IGT-SFN group was 69.78 ± 14.03uS, which was significantly lower than that in the CTRL group. The pNF-H in the IGT-SFN group was 170.6 (140.0, 223.6) pg/ml, which was significantly higher than those in the CTRL and IGT-non-SFN groups (76.55 and 64.7 pg/ml, respectively). Multivariate regression analysis demonstrated that pNF-H and 2h plasma glucose were independently correlated with SFN; the ORs (95% CI) were 1.429 (1.315, 1.924) and 2.375 (1.157, 4.837), respectively.ConclusionsSerum pNF-H may be associated with SFN in IGT patients, and serum pNF-H could therefore serve as a sensitive biomarker for the detection of SFN.

Chronic Central Pain Among Community-Dwelling Survivors of Moderate-to-Severe Traumatic Brain Injury: A Quantitative Sensory Testing Study.

Central pain associated with changes in sensory thresholds is one of the most enduring consequences of major trauma. Yet it remains sparsely studied among community-dwelling survivors of moderate-to-severe traumatic brain injury (TBI). To describe and compare thermal and mechanical sensory thresholds in home-based patients with and without central pain after moderate-to-severe TBI with a cohort of healthy controls. Cross-sectional. Thresholds for cold/heat detection, thermal pain, touch, and distorted sensation were gathered using quantitative sensory testing (QST). QST was performed on the painful and contralateral pain-free body regions in TBI participants with pain (TBI-P) and on both forearms in TBI participants without pain (TBI-NP) and healthy controls (HC). Central pain was characterized using the Brief Pain Inventory-Short Form. We tested 16 TBI-P patients, 17 TBI-NP patients, and 16 HC. Mean time since injury for TBI patients was 24 ± 15 months. TBI-P and TBI-NP patients showed significant loss in innocuous mechanical sensitivity compared to HC (F = 18.929; Bonferroni-adjusted p ≤ .001). Right-left differences in cold pain sensations were significantly larger in TBI-P than in TBI-NP and HC participants (F = 14.352; Bonferroni-adjusted p ≤ .001). Elevated heat sensitivity thresholds were also observed in TBI-P participants but remained within normal range. Damage to cutaneous mechanoreceptors is a necessary, but not sufficient, condition for the development of chronic central pain following TBI. Damage or incomplete recovery of cutaneous thermoreceptors may be a contributing factor to chronic pain after TBI.