Somatosensory Sensitivity Research Articles

A review of assessment methods for measuring individual differences in oral somatosensory perception.

While taste and smell perception have been thoroughly investigated, our understanding of oral somatosensory perception remains limited. Further, assessing and measuring individual differences in oral somatosensory perception pose notable challenges. This review aimed to evaluate the existing methods to assess oral somatosensory perception by examining and comparing the strengths and limitations of each method. The review highlighted the lack of standardized assessment methods and the various procedures within each method. Tactile sensitivity can be assessed using several methods, but each method measures different tactile dimensions. Further investigations are needed to confirm its correlation with texture sensitivity. In addition, measuring a single textural attribute may not provide an overall representation of texture sensitivity. Thermal sensitivity can be evaluated using thermal-change detection or temperature discrimination tests. The chemesthetic sensitivity tests involve either localized or whole-mouth stimulation tests. The choice of an appropriate method for assessing oral somatosensory sensitivity depends on several factors, including the specific research objectives and the target population. Each method has its unique intended purpose, strengths, and limitations, so no universally superior approach exists. To overcome some of the limitations associated with certain methods, the review offers alternative or complementary approaches that could be considered. Researchers can enhance the comprehensive assessment of oral somatosensory sensitivity by carefully selecting and potentially combining methods. In addition, a standardized protocol remains necessary for each method.

The location of pain in cluster headache: Data from the International Cluster Headache Questionnaire.

To identify the most common locations of cluster headache pain from an international, non-clinic-based survey of participants with cluster headache, and to compare these locations to other cluster headache features as well as to somatotopic maps of peripheral, brainstem, thalamic, and cortical areas. Official criteria for cluster headache state pain in the orbital, supraorbital, and/or temporal areas, yet studies have noted pain extending beyond these locations, and the occipital nerve appears relevant, given the effectiveness of suboccipital corticosteroid injections and occipital nerve stimulation. Furthermore, cranial autonomic features vary between patients, and it is not clear if the trigeminovascular reflex is dermatome specific (e.g., do patients with maxillary or V2 division pain have more rhinorrhea?). Finally, functional imaging studies show early activation of the posterior hypothalamus in a cluster headache attack. However, the first somatosensory area to be sensitized is unclear; the first area can be hypothesized based on the complete map of pain locations. The International Cluster Headache Questionnaire was an internet-based cross-sectional survey that included a clickable pain map of the face. These data were compared to several other datasets: (1) a meta-analysis of 22 previous publications of pain location in cluster headache (consisting of 6074 patients); (2) four cephalic dermatome maps; (3) participants' survey responses for demographics, autonomic features, and effective medications; and (4) previously published somatotopic maps of the brainstem, thalamus, primary somatosensory cortex, and higher order somatosensory cortex. One thousand five hundred eighty-nine participants completed the pain map portion of the survey, and the primary locations of pain across all respondents was the orbital, periorbital, and temporal areas with a secondary location in the lower occiput; these primary and secondary locations were consistent with our meta-analysis of 22 previous publications. Of the four cephalic dermatomes (V1, V2, V3, and a combination of C2-3), our study found that most respondents had pain in two or more dermatomes (range 85.7% to 88.7%, or 1361-1410 of 1589 respondents, across the four dermatome maps). Dermatomes did not correlate with their respective autonomic features or with medication effectiveness. The first area to be sensitized in the canonical somatosensory pathway is either a subcortical (brainstem or thalamus) or higher order somatosensory area (parietal ventral or secondary somatosensory cortices) because the primary somatosensory cortex (area 3b) and somatosensory area 1 have discontinuous face and occipital regions. The primary pain locations in cluster headache are the orbital, supraorbital, and temporal areas, consistent with the official International Classification of Headache Disorders criteria. However, activation of the occiput in many participants suggests a role for the occipital nerve, and the pain locations suggest that somatosensory sensitization does not start in the primary somatosensory cortex.

Recording the tactile P300 with the cEEGrid for potential use in a brain-computer interface.

Brain-computer interfaces (BCIs) are scientifically well established, but they rarely arrive in the daily lives of potential end-users. This could be in part because electroencephalography (EEG), a prevalent method to acquire brain activity for BCI operation, is considered too impractical to be applied in daily life of end-users with physical impairment as an assistive device. Hence, miniaturized EEG systems such as the cEEGrid have been developed. While they promise to be a step toward bridging the gap between BCI development, lab demonstrations, and home use, they still require further validation. Encouragingly, the cEEGrid has already demonstrated its ability to record visually and auditorily evoked event-related potentials (ERP), which are important as input signal for many BCIs. With this study, we aimed at evaluating the cEEGrid in the context of a BCI based on tactually evoked ERPs. To compare the cEEGrid with a conventional scalp EEG, we recorded brain activity with both systems simultaneously. Forty healthy participants were recruited to perform a P300 oddball task based on vibrotactile stimulation at four different positions. This tactile paradigm has been shown to be feasible for BCI repeatedly but has never been tested with the cEEGrid. We found distinct P300 deflections in the cEEGrid data, particularly at vertical bipolar channels. With an average of 63%, the cEEGrid classification accuracy was significantly above the chance level (25%) but significantly lower than the 81% reached with the EEG cap. Likewise, the P300 amplitude was significantly lower (cEEGrid R2-R7: 1.87 μV, Cap Cz: 3.53 μV). These results indicate that a tactile BCI using the cEEGrid could potentially be operated, albeit with lower efficiency. Additionally, participants' somatosensory sensitivity was assessed, but no correlation to the accuracy of either EEG system was shown. Our research contributes to the growing amount of literature comparing the cEEGrid to conventional EEG systems and provides first evidence that the tactile P300 can be recorded behind the ear. A BCI based on a thus simplified EEG system might be more readily accepted by potential end-users, provided the accuracy can be substantially increased, e.g., by training and improved classification.

Genetic background and sex influence somatosensory sensitivity and oxycodone analgesia in the Hybrid Rat Diversity Panel.

Opioid use disorder (OUD) is an ongoing public health concern in the United States, and relatively little work has addressed how genetic background contributes to OUD. Understanding the genetic contributions to oxycodone-induced analgesia could provide insight into the early stages of OUD development. Here, we present findings from a behavioral phenotyping protocol using several inbred strains from the Hybrid Rat Diversity Panel. Our behavioral protocol included a modified "up-down" von Frey procedure to measure inherent strain differences in the sensitivity to a mechanical stimulus on the hindpaw. We also performed the tail immersion assay, which measures the latency to display tail withdrawal in response to a hot water bath. Initial withdrawal thresholds were taken in drug-naïve animals to record baseline thermal sensitivity across the strains. Oxycodone-induced analgesia was measured after administration of oxycodone over the course of 2 h. Both mechanical and thermal sensitivity are shaped by genetic factors and display moderate heritability (h2 = 0.23-0.40). All strains displayed oxycodone-induced analgesia that peaked at 15-30 min and returned to baseline by 2 h. There were significant differences between the strains in the magnitude and duration of their analgesic response to oxycodone, although the heritability estimates were quite modest (h2 = 0.10-0.15). These data demonstrate that genetic background confers differences in mechanical sensitivity, thermal sensitivity, and oxycodone-induced analgesia.

Decoding Human Somatosensory Sensitivity Through Resting EEG and Behavioral Analysis: A Multimodal Fusion Approach.

In precision medicine and clinical pain management, the creation of quantitative, objective indicators to assess somatosensory sensitivity was essential. This study proposed a fusion approach for decoding human somatosensory sensitivity, which combined multimodal (quantitative sensory test and neurophysiology) features to classify the dataset on individual somatosensory sensitivity and reveal distinct types of brain activation patterns. Sixty healthy participants took part in the experiment on somatosensory sensitivity that implemented cold, heat, mechanical punctate, and pressure stimuli, and the resting-state electroencephalography (EEG) was collected using BrainVision. The quantitative sensory testing (QST) scores of the participants were clustered using the unsupervised k-means algorithm into four subgroups: generally hypersensitive (HS), generally non-sensitive (NS), predominantly thermally sensitive (TS), and predominantly mechanically sensitive (MS). Furthermore, two types of power spectral density (PSD), band-based PSD (BB-PSD) and frequency-based PSD (FB-PSD), and two types of inter-electrode connectivity (IEC), band-based connectivity (BBC) and frequency-based connectivity (FBC), derived from resting-state EEG were subjected to feature selection with a proposed prior-compared minimum-redundancy maximum-relevance (PCMRMR) protocol. Their effectiveness was then tested by the supervised classification tasks using support vector machine (SVM), k-nearest neighbor (kNN), random forest (RF), and Gaussian classifier (GC). Brain networks of four somatosensory types were revealed by decoding fused multimodal data, namely type-averaged connectivity. The data from sixty healthy individuals were divided into training (n =59) and validation (n =1) datasets according to leave-one-subject-out (LOSO) criteria. The FBC was identified, which can serve as better brain signatures than BB-PSD, FB-PSD, and BBC to classify subjects as HS, NS, TS, or MS groups. Using the SVM, kNN, RF, and GC models, the best accuracy of 87% was obtained when classifying participants into HS, NS, TS, or MS groups. Moreover, the brain networks were decoded from HS, NS, TS, and MS groups by decoding the type-averaged connectivity fused from somatosensory phenotypes and selected FBC. It indicated that quantified multi-parameter somatosensory sensitivity could be achieved with acceptable accuracy, leading to considerable possibilities for using objective pain perception evaluation in clinical practice.

Predictive and concurrent validity of pain sensitivity phenotype, neuropeptidomics and neuroepigenetics in the MI-RAT osteoarthritic surgical model in rats.

Micro-RNAs could provide great insights about the neuropathological mechanisms associated with osteoarthritis (OA) pain processing. Using the validated Montreal Induction of Rat Arthritis Testing (MI-RAT) model, this study aimed to characterize neuroepigenetic markers susceptible to correlate with innovative pain functional phenotype and targeted neuropeptide alterations. Functional biomechanical, somatosensory sensitization (peripheral-via tactile paw withdrawal threshold; central-via response to mechanical temporal summation), and diffuse noxious inhibitory control (via conditioned pain modulation) alterations were assessed sequentially in OA (n = 12) and Naïve (n = 12) rats. Joint structural, targeted spinal neuropeptides and differential expression of spinal cord micro-RNAs analyses were conducted at the sacrifice (day (D) 56). The MI-RAT model caused important structural damages (reaching 35.77% of cartilage surface) compared to the Naïve group (P < 0.001). This was concomitantly associated with nociceptive sensitization: ipsilateral weight shift to the contralateral hind limb (asymmetry index) from -55.61% ± 8.50% (D7) to -26.29% ± 8.50% (D35) (P < 0.0001); mechanical pain hypersensitivity was present as soon as D7 and persisting until D56 (P < 0.008); central sensitization was evident at D21 (P = 0.038); pain endogenous inhibitory control was distinguished with higher conditioned pain modulation rate (P < 0.05) at D7, D21, and D35 as a reflect of filtrated pain perception. Somatosensory profile alterations of OA rats were translated in a persistent elevation of pro-nociceptive neuropeptides substance P and bradykinin, along with an increased expression of spinal miR-181b (P = 0.029) at D56. The MI-RAT OA model is associated, not only with structural lesions and static weight-bearing alterations, but also with a somatosensory profile that encompasses pain centralized sensitization, associated to active endogenous inhibitory/facilitatory controls, and corresponding neuropeptidomic and neuroepigenetic alterations. This preliminary neuroepigenetic research confirms the crucial role of pain endogenous inhibitory control in the development of OA chronic pain (not only hypersensitivity) and validates the MI-RAT model for its study.

Neural indices of multimodal sensory and autonomic hyperexcitability in fibromyalgia

Fibromyalgia (FM) is characterized by chronic widespread musculoskeletal pain and psychological distress. Research suggests people with FM experience increased somatosensory sensitization which generalizes to other sensory modalities and may indicate neural hyperexcitability. However, the available evidence is limited, and studies including measures of neural responsivity across sensory domains and both central and peripheral aspects of the neuraxis are lacking. Thirty-nine participants (51.5 ± 13.6 years of age) with no history of neurological disorders, psychosis, visual, auditory, or learning deficits, were recruited for this study. People with FM (N = 19) and control participants (CNT, N = 20) did not differ on demographic variables and cognitive capacity. Participants completed a task that combined innocuous auditory stimuli with electrocutaneous stimulation (ECS), delivered at individually-selected levels that were uncomfortable but not painful. Event-related potentials (ERPs) and electrodermal activity were analyzed to examine the central and sympathetic indices of neural responsivity. FM participants reported greater sensitivity to ECS and auditory stimulation, as well as higher levels of depression, anxiety, ADHD, and an array of pain-related experiences than CNT. In response to ECS, the P50 deflection was greater in FM than CNT participants, reflecting early somatosensory hyperexcitability. The P50 amplitude was positively correlated with the FM profile factor obtained with a principal component analysis. The N100 to innocuous tones and sympathetic reactivity to ECS were greater in FM participants, except in the subgroup treated with gabapentinoids, which aligns with previous evidence of symptomatic improvement with GABA-mimetic medications. These results support the principal tenet of generalized neural hyperexcitability in FM and provide preliminary mechanistic insight into the impact of GABA-mimetic pharmacological therapy on ameliorating the neural excitation dominance.

Effect of Sustained Jaw Opening on Fatigue, Pressure Pain Sensations, and Stiffness in the Masticatory Muscles

Although the effects of sustained jaw-closing activities on somatosensory sensitivity and fatigue have been investigated, the effects of sustained jaw-opening activities on somatosensory sensitivity in the masticatory muscles remain unclear. Therefore, this study aimed to investigate the effects of sustained jaw opening（e.g. during dental treatment）on fatigue, pressure pain sensations, and stiffness in the masticatory muscles. A total of 35 healthy volunteers performed 30 minutes each of two jaw motor tasks, with a 1-week interval between tasks: unassisted jaw opening and jaw opening assisted by a mouth prop set at the right tooth. The pressure pain threshold（PPT）and muscle stiffness of the left masseter were measured before and after both jaw motor tasks（at 0 and 30 minutes）. Masticatory muscle fatigue was measured every 10 minutes（at 0, 10, 20, and 30 minutes）during each jaw motor task. No significant differences in the PPT were found between before and after the assisted jaw-opening task, but the PPT was significantly lower after compared with before unassisted jaw opening（P < 0.05）. No significant differences in left masseter muscle stiffness were found between any measurement point in either jaw motor task. Masticatory muscle fatigue was significantly higher after 10, 20, and 30 minutes of each jaw motor task compared with that at baseline（0 minutes）. However, no significant differences in masticatory muscle fatigue were found at any measurement point between both jaw motor tasks. The present results suggest that sustained jaw opening during dental treatment may affect pressure pain sensations in the masticatory muscles. In addition, masticatory muscle pain due to sustained jaw opening seems to be affected not only by jaw-opening but also jaw-closing muscle（masseter muscle）.

Alterations of Handgrip Strength in Type 2 Diabetes Mellitus Patients

Background:Peripheral Neuropathy is most prevalent chronic complication in diabetes.Diabetes affect sensory andmotor function including progressive loss of somatosensory sensitivity,Insufficient muscle strength and functionalImpairment.Objective of this study isto Analyse Hand grip strength in Diabetes patients with or without Neuropathy.Methods:Descriptive study in Government medical college Thoothukudi,100 Patients attending Outpatient Departmentfor Diabetes were analysed.Duration of study 6 months.Demographic data and medical history was noted afterinformed consent.Michigan Neuropathy Screening Instrument applied.Hand grip was tested using Electronic digitalhand Dynamometer and compared with 40 age matched healthy volunteers.Findings described in simple descriptivemanner.SPSS version 24 used for statistical analysis.Results:Mean Age 62.40+/-6.435 Vs Control group 58.55+/-6.921.Male 58%,Female 42%.Between 45-54yrs(8%),55-64yrs(62%),65-75yrs(30%).Mean duration of diabetes 8.31+/-2.770 years.Michigan Neuropathy Screening Instrumentscore mean 4.98+/-1.484.Mean Hand grip Right hand(kg) 20.723+/-7.688 Vs Control 24.978+/-7.1427.Mean Handgrip Left hand(kg) 19.153+/-7.2436 vs Control 22.890+/-6.8664.Mean Hand grip right hand male compared to control45-54yrs(27.66+/-6.63 vs 35.34+/-4.16),55-64yrs(27.14+/-6.31 vs30.95+/-2.55)65-75yrs(16.47+/-5.89 vs 21.24+/-2.32).Mean hand grip female 45-54yrs(18.2+/-4.79 vs 26.74+/-3.17),55-64yrs(17.22+/-4.63 vs 19.88+/-2.14),65-75yrs(13.34+/-2.85 vs 14.84+/-1.16).Conclusions:Handgrip strength is lower in participants with Diabetes compared to age matched controls.Mean handgrip values also showed decrease with age in both study participants and healthy volunteers.

Post-Injury Buprenorphine Administration Is Associated with Long-Term Region-Specific Glial Alterations in Rats.

Traumatic brain injury (TBI) is a major leading cause of death and disability. While previous studies regarding focal pathologies following TBI have been done, there is a lack of information concerning the role of analgesics and their influences on injury pathology. Buprenorphine (Bup), an opioid analgesic, is a commonly used analgesic in experimental TBI models. Our previous studies investigated the acute effects of Buprenorphine-sustained release-Lab (Bup-SR-Lab) on diffuse neuronal/glial pathology, neuroinflammation, cell damage, and systemic physiology. The current study investigated the longer-term chronic outcomes of Bup-SR-Lab treatment at 4 weeks following TBI utilizing a central fluid percussion injury (cFPI) model in adult male rats. Histological assessments of physiological changes, neuronal damage, cortical and thalamic cytokine expression, microglial and astrocyte morphological changes, and myelin alterations were done, as we had done in our acute study. In the current study the Whisker Nuisance Task (WNT) was also performed pre- and 4w post-injury to assess changes in somatosensory sensitivity following saline or Bup-SR-Lab treatment. Bup-SR-Lab treatment had no impact on overall physiology or neuronal damage at 4w post-injury regardless of region or injury, nor did it have any significant effects on somatosensory sensitivity. However, greater IL-4 cytokine expression with Bup-SR-Lab treatment was observed compared to saline treated animals. Microglia and astrocytes also demonstrated region-specific morphological alterations associated with Bup-SR-Lab treatment, in which cortical microglia and thalamic astrocytes were particularly vulnerable to Bup-mediated changes. There were discernable injury-specific and region-specific differences regarding myelin integrity and changes in specific myelin basic protein (MBP) isoform expression following Bup-SR-Lab treatment. This study indicates that use of Bup-SR-Lab could impact TBI-induced glial alterations in a region-specific manner 4w following diffuse brain injury.

Identifying potential training factors in a vibrotactile P300-BCI

Brain–computer interfaces (BCI) often rely on visual stimulation and feedback. Potential end-users with impaired vision, however, cannot use these BCIs efficiently and require a non-visual alternative. Both auditory and tactile paradigms have been developed but are often not sufficiently fast or accurate. Thus, it is particularly relevant to investigate if and how users can train and improve performance. We report data from 29 healthy participants who trained with a 4-choice tactile P300-BCI during five sessions. To identify potential training factors, we pre-post assessed the robustness of the BCI performance against increased workload in a dual task condition and determined the participants’ somatosensory sensitivity thresholds with a forced-choice intensity discrimination task. Accuracy (M = 79.2% to 92.0%) and tactually evoked P300 amplitudes increased significantly, confirming successful training. Pre-post somatosensory sensitivity increased, and workload decreased significantly, but results of the dual task condition remained inconclusive. The present study confirmed the previously reported feasibility and trainability of our tactile BCI paradigm within a multi-session design. Importantly, we provide first evidence of improvement in the somatosensory system as a potential mediator for the observed training effects.

Role of the DUB enzyme USP7 in dendritic arborization, neuronal migration, and autistic-like behaviors in mice

SummaryDuplication and haploinsufficiency of the USP7 gene are implicated in autism spectrum disorders (ASD), but the role for USP7 in neurodevelopment and contribution to ASD pathogenesis remain unknown. We find that in primary neurons, overexpression of USP7 increases dendritic branch number and total dendritic length, whereas knockdown leads to opposite alterations. Besides, USP7 deubiquitinates the X-linked inhibitor of apoptosis protein (XIAP). The USP7-induced increase in XIAP suppresses caspase 3 activity, leading to a reduction in tubulin cleavage and suppression of dendritic pruning. When USP7 is introduced into the brains of prenatal mice via in utero electroporation (IUE), it results in abnormal migration of newborn neurons and increased dendritic arborization. Importantly, intraventricular brain injection of AAV-USP7 in P0 mice leads to autistic-like phenotypes including aberrant social interactions, repetitive behaviors, as well as changes in somatosensory sensitivity. These findings provide new insights in USP7-related neurobiological functions and its implication in ASD.

Association between somatosensory sensitivity and regional gray matter volume in healthy young volunteers: a voxel-based morphometry study.

Two-point discrimination (2PD) test reflects somatosensory spatial discrimination ability, but evidence on the relationship between 2PD and cortical gray matter (GM) volume is limited. This study aimed to analyze the relationship between cortical GM volume and 2PD threshold in young healthy individuals and to clarify the characteristics of brain structure reflecting the individual differences in somatosensory function. 2PD was measured in 42 healthy (20 females) volunteers aged 20-32years using a custom-made test system that can be controlled by a personal computer. The 2PD of the right index finger measured with this device has been confirmed to show good reproducibility. T1-weighted images were acquired using a 3-T magnetic resonance imaging scanner for voxel-based morphometry analysis. The mean 2PD threshold was 2.58 ± 0.54mm. Whole-brain multiple regression analysis of the relationship between 2PD and GM volume showed that a lower 2PD threshold (i.e. better somatosensory function) significantly correlated with decreased GM volume from the middle temporal gyrus to the inferior parietal lobule (IPL) in the contralateral hemisphere. In conclusion, a lower GM volume in the middle temporal gyrus and IPL correlates with better somatosensory function. Thus, cortical GM volume may be a biomarker of somatosensory function.

P.0141 Investigating the relationship between affective state, stress, somatosensory sensitivity, and endocannabinoids in healthy human participants: a pilot study

P.0141 Investigating the relationship between affective state, stress, somatosensory sensitivity, and endocannabinoids in healthy human participants: a pilot study

An Observational Study Comparing Fibromyalgia and Chronic Low Back Pain in Somatosensory Sensitivity, Motor Function and Balance.

Fibromyalgia (FM) and chronic low back pain (CLBP) have shared pathophysiology and have a considerable impact on patients’ daily activities and quality of life. The main objective of this study was to compare pain impact, somatosensory sensitivity, motor functionality, and balance among 60 patients with FM, 60 patients with CLBP, and 60 pain-free controls aged between 30 and 65 years. It is essential to know the possible differences existing in symptomatology of two of the major chronic pain processes that most affect the population, such as FM and CLBP. The fact of establishing possible differences in sensory thresholds, motor function, and proprioceptive measures among patients with FM and CLBP could bring us closer to a greater knowledge of the chronic pain process. Through an observational study, a comparison was made between the three groups (FM, CLBP, and pain-free controls) evaluating functional performance, postural balance, kinematic gait parameters, strength, depression, fatigue, and sensitivity to pain and vibration. Patients with chronic pain showed worse somatosensory sensitivity (p < 0.001) and motor function (p < 0.001) than pain-free controls. Moreover, patients with FM showed greater pain impact (p < 0.001) and bigger somatosensory (p < 0.001) and motor deficiencies (p < 0.001) than patients with CLBP. Further research should explore the possible reasons for the greater deterioration in patients with FM in comparison with other chronic pain conditions. Our results, showing the multiple areas susceptible of deterioration, make it necessary to adopt interdisciplinary interventions focused both on physical and emotional dysfunction.

Oral Somatosensory Sensitivity in Patients With Taste Disturbance.

The significance of the human sense of taste is typically underestimated until it is altered or even lost. Hypogeusia, a diminished capacity to taste, has an adverse influence on a patient's quality of life. Similar to interactions between the oral senses and between olfaction and intranasal trigeminal sensitivity, taste disturbance may also affect the mechanosensitivity of the tongue. In this study, we investigated the lingual tactile sensitivity of patients with subjective taste disturbance and people with normogeusia. Prospective case-control study. Forty-six patients with subjective taste disturbance (mean age 60 years) and 43 participants with normogeusia (mean age 55 years) were enrolled and underwent a stereognostic test of edge and point sensitivity based on 3D-printed letters sized from 2 to 8 mm. Gustatory function and salivary production were also tested. Patients with dysgeusia needed significantly bigger letters to recognize them compared with controls (P=.01). Apart from this, patients with dysgeusia had no significant association between gustatory function and salivary production. Duration of dysgeusia and age were not associated with the presently obtained measures of gustatory or oral mechanosensory function. The results of this study indicate that taste dysfunction has a negative impact on oral mechanosensitivity and hence possibly on oral texture perception. 3 Laryngoscope, 131:2572-2577, 2021.

Behavioral phenotyping of cancer pain in domesticated cats with naturally occurring squamous cell carcinoma of the tongue: initial validation studies provide evidence for regional and widespread algoplasticity.

Feline oral squamous cell carcinoma (FOSCC) is a common and naturally occurring condition that recapitulates many features of human head and neck cancer (HNC). In both species, there is need for improved strategies to reduce pain caused by HNC and its treatment. Research to benefit both species could be conducted using pet cats as a comparative model, but this prospect is limited by lack of validated methods for quantifying FOSCC-associated pain. A prospective non-randomized pilot study was performed for initial validation of: (1) a pet owner administered quality of life questionnaire and visual assessment scoring tool (FORQ/CLIENT); (2) a clinician assessment questionnaire (UFEPS/VET); (3) electronic von Frey testing [EVF]; and (4) Cochet-Bonnet (COBO) aesthesiometry. To assess intra-rater reliability, discriminatory ability, and responsiveness of each assay, 6 cats with sublingual SCC and 16 healthy control cats were enrolled. The intra-rater reliability was moderate-to-good for the clinical metrology instruments and EVF (intraclass correlation coefficient [ICC] ≥ 0.68), but poor for COBO (ICC = 0.21). FORQ/CLIENT scores were higher (worse quality of life) in FOSCC cats vs healthy controls. The internal reliability of FORQ/CLIENT scoring was high (Cronbach α = 0.92); sensitivity and specificity were excellent (100% when using cut-offs determined using receiver operating characteristic [ROC] curves). For the FORQ/CLIENT, there was strong and inverse correlation between scores from the questions and visual assessment (r = − 0.77, r2 = 0.6, P < 0.0001). For the UFEPS/VET, Cronbach’s α was 0.74 (high reliability). Sensitivity and specificity were 100% and 94%, respectively, when using a cut-off score (3.5) based on ROC curves (Youden index of 0.94). Total UFEPS/VET scores were positively correlated with FORQ/CLIENT scores (r2 = 0.72, P < 0.0001). Sensitivity of EVF and COBO ranged from 83 to 100% and specificity ranged from 56 to 94%. Cats with cancer were more sensitive around the face (lower response thresholds) and on the cornea (longer filament lengths) than control animals (P < 0.03). Reduced pressure response thresholds were also observed at a distant site (P = 0.0002) in cancer cats. After giving buprenorphine, EVF pressure response thresholds increased (P = 0.04) near the mandible of cats with OSCC; the length of filament required to elicit a response in the COBO assay also improved (shortened; P = 0.017). Based on these preliminary assessments, the assays described herein had reasonable inter-rater reliability, and they were able to both discriminate between cats with and without oral cancer, and respond in a predictable manner to analgesic therapy. In cats with tongue cancer, there was evidence for regional peripheral sensitization, and widespread somatosensory sensitization. These results provide a basis for multi-dimensional assessments of pain and sensitivity in cats with oral SCC.

Estrogens influence female itch sensitivity via the spinal gastrin-releasing peptide receptor neurons

There are sex differences in somatosensory sensitivity. Circulating estrogens appear to have a pronociceptive effect that explains why females are reported to be more sensitive to pain than males. Although itch symptoms develop during pregnancy in many women, the underlying mechanism of female-specific pruritus is unknown. Here, we demonstrate that estradiol, but not progesterone, enhances histamine-evoked scratching behavior indicative of itch in female rats. Estradiol increased the expression of the spinal itch mediator, gastrin-releasing peptide (GRP), and increased the histamine-evoked activity of itch-processing neurons that express the GRP receptor (GRPR) in the spinal dorsal horn. The enhancement of itch behavior by estradiol was suppressed by intrathecal administration of a GRPR blocker. In vivo electrophysiological analysis showed that estradiol increased the histamine-evoked firing frequency and prolonged the response of spinal GRP-sensitive neurons in female rats. On the other hand, estradiol did not affect the threshold of noxious thermal pain and decreased touch sensitivity, indicating that estradiol separately affects itch, pain, and touch modalities. Thus, estrogens selectively enhance histamine-evoked itch in females via the spinal GRP/GRPR system. This may explain why itch sensation varies with estrogen levels and provides a basis for treating itch in females by targeting GRPR.

Assessment of Somatosensory Function and Self-harm in Adolescents

Self-harm is a risk factor for suicide in adolescents, with the prevalence highest in young people in group and residential care programs. Although no established risk factors for self-harm exist, adolescents who self-harm may have decreased pain sensitivity, but this has not been systematically investigated. To assess somatosensory function using quantitative sensory testing (QST) in children and adolescents living in care grouped by the number of episodes of self-harm in the past year and compare their somatosensory profiles with community control participants to investigate associations with the incidence or frequency of self-harm. Recruitment for this cross-sectional study began January 2019 and ended March 2020. Exclusion criteria included intellectual disability (intelligence quotient <70), autism spectrum disorder, or recent serious injury. Children and adolescents aged 12 to 17 years with no underlying health conditions were recruited from local authority residential care settings in Glasgow, UK, and schools and youth groups in London and Glasgow, UK. The volunteer sample of 64 participants included adolescents ages 13 to 17 years (34 [53%] females; 50 [78%] living in residential care; mean [SD] age, 16.34 [1.01] years) with varying incidents of self-harm in the past year (no episodes, 31 [48%]; 1-4 episodes, 12 [19%]; and ≥5 episodes, 2 [33%]). Participants were tested using a standardized QST protocol to establish baseline somatosensory function. Associations between somatosensory sensitivity, incidence and frequency of self-harm, residential status, age, gender, and prescription medication were calculated. Secondary outcomes assessed whether self-harm was associated with specific types of tests (ie, painful or nonpainful). A total of 64 participants ages 13 to 17 years completed testing (mean [SD] age, 16.3 [1.0] years; 34 [53%.] females and 30 [47%] males; 50 [78%] living in group homes). Adolescents with 5 or more self-harm incidences showed significant pain hyposensitivity compared with community control participants after adjusting for age, gender, and prescription drug use (SH group with 5 or more episodes vs control: -1.03 [95% CI, -1.47 to -0.60]; P < .001). Hyposensitivity also extended to nonpainful stimuli, similarly adjusted (SH group with 5 or more episodes vs control: -1.73; 95% CI, -2.62 to -0.84; P < .001). Pressure pain threshold accounted for most of the observed variance (31.1% [95% CI, 10.5% to 44.7%]; P < .001). The findings of this study suggest that sensory hyposensitivity is a phenotype of Adolescents who self-harm and that pressure pain threshold has clinical potential as a quick, inexpensive, and easily interpreted test to identify adolescents at increased risk of repeated self-harm.

Drop homotopic effects of masseter-muscle pain on somatosensory sensitivity in healthy participants

Current pain classifications use 1.0-kg palpation of the masseter muscle to distinguish between “pain patients” and “healthy controls” but a thorough understanding of the normal physiological responses to various somatosensory stimuli is lacking. The aim of this study was to investigate somatosensory function of the skin over the masseter muscle in healthy participants that were divided into a masseter pain prone group (MPP) (n = 22) and non-MPP group (n = 22), according to the response to a 1.0-kg palpation. Quantitative sensory testing (QST) was performed at the skin above the right masseter muscle (homotopic). In an additional experiment, 13 individuals each from MPP and non-MPP received application of 60% topical lidocaine tape to the skin over the masseter muscle for 30 min. Immediately after, mechanical pain sensitivity (MPS), dynamic mechanical allodynia, and pressure pain threshold were tested. Homotopic MPS was significantly higher and PPTs significantly lower in MPP than in N-MPP (P < 0.05). Strikingly, no other differences in QST outcomes were observed between the groups (P > 0.05). After lidocaine application, no significant differences in homotopic MPS were observed between groups. The presence or absence of acute provoked pain in masseter muscle is exclusively associated with differences in homotopic MPS which is decreased following topical anesthesia.