Somatic Modulation Research Articles

Pilot study on the role of somatic modulation in hyperacusis.

Hyperacusis is a reduced tolerance to sounds that often co-occurs with tinnitus. Both symptoms have convergent as well as divergent characteristics. Somatic modulation, changes in pitch or loudness during certain movements, is common in patients with a primary complaint of tinnitus. However, thus far, this is not documented in patients with hyperacusis. This study aimed to examine the influence of somatic manoeuvres on the perception of external sounds in patients with a primary complaint of hyperacusis. In this prospective cross-sectional pilot study, 18 patients with a primary complaint of hyperacusis were recruited at the Tinnitus Treatment and Research Center Antwerp (TINTRA). While patients listened to a 1kHz broadband noise of 30dB sensation level, six neck manoeuvres (flexion, extension, lateroflexion left/right, traction and compression), three jaw manoeuvres (protrusion, laterotrusion left/right) and one placebo manoeuvre (hand on head) were performed. The primary outcome measure was the change in the perception of the presented sound in terms of loudness and intrusiveness between baseline and each modulation measured by a visual analogue scale (VAS). No overall significant changes were found; however, individual results indicated that five patients presented a clinically relevant change of more than three points out of ten on VAS in terms of hyperacusis after at least one of the executed somatic manoeuvres. This pilot study did not demonstrate an overall significant change in hyperacusis after somatic manoeuvres but does not rule out the possibility of somatic modulation in some hyperacusis patients. The protocol of this prospective cross-sectional pilot study was registered on clinicaltrials.gov with registration number NCT04693819.

The Rapid Screening for Somatosensory Tinnitus Tool: a Data-Driven Decision Tree Based on Specific Diagnostic Criteria.

Somatosensory or somatic tinnitus (ST) is a type of tinnitus where changes in somatosensory afference from the cervical spine or temporomandibular area alter the tinnitus perception. Very recently, the diagnostic value of a set of 16 diagnostic criteria for ST was determined. The next step in the development of easily applicable diagnostic criteria is to provide an uncomplicated model, based on the existing criteria, which can easily be used in clinical practice. This study aims to construct an accurate decision tree, combining several diagnostic criteria, to optimize both sensitivity and specificity of ST diagnosis. An online survey was launched on the online forum Tinnitus Talk, managed by Tinnitus Hub in a convenience sample of participants with tinnitus. The survey included 42 questions, both on the presence of diagnostic criteria for ST and on other potentially influencing factors. A decision tree was constructed to classify participants with and without ST using the rpart package in R. Tree depth was optimized during a five-fold cross-validation. Finally, model performance was evaluated on a subset containing 20% of the original dataset. Data of 7981 participants were used to construct a decision tree for ST diagnosis. Four criteria were included in the final decision tree: 'Tinnitus and neck/jaw pain increase/decrease simultaneously', 'Tension in suboccipital muscles', 'Somatic modulation', and 'Bruxism'. The presented model has an accuracy of 82.2%, a sensitivity of 82.5%, and a specificity of 79%. Receiver operator characteristic curves demonstrated an area under the curve of 0.88. Based on a 42-item survey, a decision tree was created that was able to detect ST patients with high accuracy (82.2%) using only 4 questions. The RaSST is therefore expected to be easily implementable in clinical practice.

Impact of Temporomandibular Joint Complaints on Tinnitus-Related Distress

There is increasing evidence of associations between the presence of temporomandibular joint (TMJ) disorders and tinnitus. It has been recently proposed that tinnitus patients with TMJ complaints could constitute a subtype, meaning a subgroup of tinnitus patients responsive to specific treatments. Tinnitus patients with TMJ complaints are often young women with somatosensory features of their tinnitus. Here, we investigate the socio-economic factors, phenotypic characteristics and psychological variables of tinnitus subjects from the Swedish Tinnitus Outreach Project, with (n = 486) or without (n = 1,996) TMJ complaints. The prevalence of TMJ complaints was greater in tinnitus subjects with severe tinnitus (36%) when compared to those with any tinnitus (19%), strongly indicating the contribution of TMJ problems to the severity of tinnitus. Comparing subgroups with or without TMJ complaints in the whole sample, differences were found regarding a large number of socioeconomic, phenotypic, and psychological characteristics. Subjects with TMJ complaints were more often women, more often reported stress as the cause of tinnitus, were more severely affected by tinnitus, scored worse in measures of psychological well-being and life quality, and were more often affected by problems tolerating sounds, headache, vertigo/dizziness, and neck pain. In addition, they more often reported pulsating and tonal tinnitus, somatic modulation of tinnitus, and aggravation of tinnitus by loud sounds and stress. When focusing the analysis in subjects with tinnitus as a big problem using the Tinnitus Functional Index cut-off ≥ 48, or with severe tinnitus according to the Tinnitus Handicap Inventory cut-off ≥ 58, the impact of somatosensory modulations and stress on tinnitus were greater in subjects with TMJ complaints in comparison to those without. In light of these results, we hypothesize that stress could contribute to the co-occurrence of TMJ problems and tinnitus and also to the development of severe tinnitus. Our study supports the need of involving dental care and stress management in the holistic treatment of patients with severe tinnitus.

Somatic modulation of ectopic action potential initiation in distal axons.

Somatic modulation of ectopic action potential initiation in distal axons.

Characteristics of somatic tinnitus patients with and without hyperacusis.

ObjectiveDetermine if somatic tinnitus patients with hyperacusis have different characteristics from those without hyperacusis.Patients and methods172 somatic tinnitus patients with (n = 82) and without (n = 90) hyperacusis referred to the Tinnitus Unit of Sapienza University of Rome between June 2012 and June 2016 were compared for demographic characteristics, tinnitus features, self-administered questionnaire scores, nature of somatic modulation and history.ResultsCompared to those without hyperacusis, patients with somatic tinnitus and hyperacusis: (a) were older (43.38 vs 39.12 years, p = 0.05), (b) were more likely to have bilateral tinnitus (67.08% vs 55.56%, p = 0.04), (c) had a higher prevalence of somatic modulation of tinnitus (53.65% vs 36.66%, p = 0.02) and (d) scored significantly worse on tinnitus annoyance (39.34 vs 22.81, p<0.001) and subjective hearing level (8.04 vs 1.83, p<0.001).ConclusionOur study shows significantly higher tinnitus modulation and worse self-rating of tinnitus and hearing ability in somatic tinnitus patients with hyperacusis versus somatic tinnitus patients without hyperacusis. These differences could prove useful in developing a better understanding of the pathophysiology and establishing a course of treatment for these two groups of patients.

Somatosensory Tinnitus: Correlation between Cranio-Cervico-Mandibular Disorder History and Somatic Modulation

In a subpopulation of patients, tinnitus can be modulated by movements of the jaw or head and neck due to complex somatosensory-auditory interactions. In some of these subjects, tinnitus could be related to an underlying temporomandibular (TMJ) or craniocervical (NECK) dysfunction that, if correctly identified, could streamline treatment and increase chances of tinnitus improvement. However, it is still unclear whether somatic modulation of tinnitus could be used as a screening tool for identifying such patients. In this study, we included 310 tinnitus patients with normal hearing, no psychiatric comorbidities, and a positive history of TMJ and/or NECK dysfunction and/or a positive modulation of tinnitus to evaluate the characteristics of somatic modulation, investigate the relationship between positive history and positive modulation, and identify factors most strongly associated with somatic modulation. Tinnitus modulation was present in 79.67% of the patients. We found a significant association within the same subjects between a positive history and a positive tinnitus modulation for the same region, mainly for TMJ in unilateral tinnitus patients and for TMJ + NECK in bilateral tinnitus patients. A strong correlation between history and modulation in the same somatic region within the same subgroups of subjects was also identified. Most TMJ maneuvers resulted in an increased loudness, while NECK maneuvers showed an increase in tinnitus loudness in about 59% of cases. High-pitched tinnitus and male gender were associated with a higher prevalence of modulation; no differences were found for tinnitus onset, Tinnitus Handicap Inventory score, and age. In this paper, we report a strong association between history and modulation for the same regions within the same patients; such an association should always be investigated to improve chances of a correct diagnosis of somatosensory tinnitus.

Somatic Tinnitus.

Modulation of tinnitus characteristics such as pitch and loudness has been extensively described following movements of the head, neck and limbs, vertical or horizontal eye gaze, pressure on myofascial trigger points, cutaneous stimulation of the hands, electrical stimulation of the median nerve, and transcranial direct current stimulation. Modulation of tinnitus follows complex interactions between auditory and somatosensory afferents and can be favored by underlying somatic disorders. When tinnitus appears to be preceded or strictly linked to a somatic disorder, and therefore related to problems of the musculoskeletal system rather than of the ear, it is defined somatic tinnitus. A correct diagnosis and treatment of somatic disorders underlying tinnitus play a central role for a correct management of somatic tinnitus. However, the identification of somatic tinnitus may be complex in some cases. In this paper, after a general review of the current evidences for somatic tinnitus available in the literature, we present and discuss some cases of patients in which somatic modulation of tinnitus played a role-although different from case to case-in their tinnitus, describing the diagnostic and therapeutic approaches followed in each individual case and the results obtained, also highlighting unexpected findings and pitfalls that may be encountered when approaching somatic tinnitus patients.

Somatic Modulation of Tinnitus: A Review and Some Open Questions

Somatic Modulation of Tinnitus: A Review and Some Open Questions

P.2.h.005 Somatic pain modulation and its role in typifying the dimension of pain in depression

with respect to suicide risk factors in CRPS patients are available. The purpose of this study was to assess risk factors for suicidal ideation in patients with CRPS and also we evaluated psychiatric comorbidity in this population. Methods: Based on criteria established by the International Association for the Study of Pain, 39 patients diagnosed with CRPS Type 1 or Type 2 were enrolled in this study. Suicidal ideation was assessed using item 3 of the Hamilton Depression Rating Scale (HAMD). The low-suicidal ideation (SI) group included those with scores of 1 or below on HAMD item 3 (0 = suicide ideation absent, 1 = feels that life is worth living), and the high-SI group included those with HAMD item 3 scores above 1. Symptoms of pain were evaluated using the short form of the McGill Pain Questionnaire (SF-MPQ). Psychiatric symptoms were assessed in using the Structured Clinical Interview for DSM-IV Disorders (SCID-I; SCID-II), the HAMD, the Hamilton Anxiety Rating Scale (HAMA), the Global Assessment of Functioning Scale (GAF), and the Pittsburgh Sleep Quality Index (PSQI). Betweengroup comparisons involving categorical data were performed using the chi-square statistic corrected for continuity; between-group comparisons involving continuous data (age and socio-economic status) were calculated using Student’s t-test. Pearson’s correlation analysis was used to assess correlations between suicidal ideation and other variables. Results: 33 (84.6%) were diagnosed with CRPS Type 1, and six (15.4%) were diagnosed with CRPS Type II. Males accounted for 61.5% (n = 24) of the patients, and females 38.5% (n = 15). The mean age of the patients at their initial evaluation at the pain clinic was 37.87 (±11.94) years, and the mean number of years of education was 12.49 (±2.68) years. Patients reported having CRPS symptoms for a mean of 2.84 years (±2.49) at the time of evaluation and had been prescribed 4.28 (range, 0−7) different kinds of medications on average. Twenty-nine patients (74.4%) were at high risk and 10 (25.6%) were at low risk for suicidal ideation. Risk factors significantly associated with suicidal ideation included depression (p= 0.002), severity of pain (p= 0.024), and low scores on the GAF (p= 0.027). No significant correlations were found between suicidal ideation and anxiety or quality of sleep. Conclusions: CRPS is recognized as one of the most difficult conditions to treat among pain syndromes. This study found that the factors most strongly associated with suicide in patients with CRPS were depression, pain severity, and general functioning. These results suggest that psychiatric evaluation and intervention should be included in the treatment of CRPS.

Activation of calcineurin underlies altered trafficking of α2 subunit containing GABAA receptors during prolonged epileptiform activity

Fast inhibitory signalling in the mammalian brain is mediated by gamma-aminobutyric acid type A receptors (GABAARs), which are targets for anti-epileptic therapy such as benzodiazepines. GABAARs undergo tightly regulated trafficking processes that are essential for maintenance and physiological modulation of inhibitory strength. The trafficking of GABAARs to and from the membrane is altered during prolonged seizures such as in Status Epilepticus (SE) and has been suggested to contribute to benzodiazepine pharmacoresistance in patients with SE. However, the intracellular signalling mechanisms that cause this modification in GABAAR trafficking remain poorly understood. In this study, we investigate the surface stability of GABAARs during SE utilising the low Mg2+ model in hippocampal rat neurons. Live-cell imaging of super ecliptic pHluorin (SEP)-tagged α2 subunit containing GABAARs during low Mg2+ conditions reveals that the somatic surface receptor pool undergoes down-regulation dependent on N-methyl-d-aspartate receptor (NMDAR) activity. Analysis of the intracellular Ca2+ signal during low Mg2+ using the Ca2+-indicator Fluo4 shows that this reduction of surface GABAARs correlates well with the timeline of intracellular Ca2+ changes. Furthermore, we show that the activation of the phosphatase calcineurin was required for the decrease in surface GABAARs in neurons undergoing epileptiform activity. These results indicate that somatic modulation of GABAAR trafficking during epileptiform activity in vitro is mediated by calcineurin activation which is linked to changes in intracellular Ca2+ concentrations. These mechanisms could account for benzodiazepine pharmacoresistance and the maintenance of recurrent seizure activity, and reveal potential novel targets for the treatment of SE.This article is part of the Special Issue entitled ‘GABAergic Signaling in Health and Disease’.

Somatic modulation of spinal reflex bladder activity mediated by nociceptive bladder afferent nerve fibers in cats.

The goal of the present study was to determine if supraspinal pathways are necessary for inhibition of bladder reflex activity induced by activation of somatic afferents in the pudendal or tibial nerve. Cats anesthetized with α-chloralose were studied after acute spinal cord transection at the thoracic T9/T10 level. Dilute (0.25%) acetic acid was used to irritate the bladder, activate nociceptive afferent C-fibers, and trigger spinal reflex bladder contractions (amplitude: 19.3 ± 2.9 cmH2O). Hexamethonium (a ganglionic blocker, intravenously) significantly (P < 0.01) reduced the amplitude of the reflex bladder contractions to 8.5 ± 1.9 cmH2O. Injection of lidocaine (2%, 1-2 ml) into the sacral spinal cord or transection of the sacral spinal roots and spinal cord further reduced the contraction amplitude to 4.2 ± 1.3 cmH2O. Pudendal nerve stimulation (PNS) at frequencies of 0.5-5 Hz and 40 Hz but not at 10-20 Hz inhibited reflex bladder contractions, whereas tibial nerve stimulation (TNS) failed to inhibit bladder contractions at all tested frequencies (0.5-40 Hz). These results indicate that PNS inhibition of nociceptive afferent C-fiber-mediated spinal reflex bladder contractions can occur at the spinal level in the absence of supraspinal pathways, but TNS inhibition requires supraspinal pathways. In addition, this study shows, for the first time, that after acute spinal cord transection reflex bladder contractions can be triggered by activating nociceptive bladder afferent C-fibers using acetic acid irritation. Understanding the sites of action for PNS or TNS inhibition is important for the clinical application of pudendal or tibial neuromodulation to treat bladder dysfunctions.

Prevalence and Factors Associated with Neck and Jaw Muscle Modulation of Tinnitus

Forceful contractions of neck and jaw muscles have consistently been shown to modulate tinnitus and can be used to screen patients who are responsive to somatic stimulation and, therefore, optimal candidates for somatosensory-based treatment. To identify the factors associated with somatic modulation of tinnitus, 163 patients underwent 19 neck and jaw maneuvers after an extensive physiological and audiological profile was compiled. Overall, tinnitus was modulated in 57.1% of ears tested. Unilateral tinnitus showed greater prevalence of modulation. Neck maneuvers generally decreased tinnitus loudness, whereas jaw maneuvers increased loudness. Female gender and buzzing tinnitus were associated with a high prevalence of modulation and a decrease in tinnitus loudness. Loud tinnitus and low-pitched tonal tinnitus were associated with exacerbation of the condition as a result of somatic testing. Use of these characteristics to select optimal candidates for somatosensory-based tinnitus therapies may be essential for the development of an effective approach for tinnitus treatment.

Effects of Axonal Topology on the Somatic Modulation of Synaptic Outputs

Depolarization of the neuronal soma augments synaptic output onto postsynaptic neurons via long-range, axonal cable properties. Here, we report that the range of this somatic influence is spatially restricted by not only axonal path length but also a branching-dependent decrease in axon diameter. Cell-attached recordings of action potentials (APs) from multiple axon branches of a rat hippocampal CA3 pyramidal cell revealed that an AP was broadened following a 20 mV depolarization of the soma and reverted to a normal width during propagation down the axon. The narrowing of the AP depended on the distance traveled by the AP and on the number of axon branch points through which the AP passed. These findings were confirmed by optical imaging of AP-induced calcium elevations in presynaptic boutons, suggesting that the somatic membrane potential modifies synaptic outputs near the soma but not long-projection outputs. Consistent with this prediction, whole-cell recordings from synaptically connected neurons revealed that depolarization of presynaptic CA3 pyramidal cells facilitated synaptic transmission to nearby CA3 pyramidal cells, but not to distant pyramidal cells in CA3 or CA1. Therefore, axonal geometry enables the differential modulation of synaptic output depending on target location.

Comparison of Clinical Characteristics and Somatic Modulation between Somatic Tinnitus and Otic Tinnitus

Aims: To compare the clinical characteristics of tinnitus among patients with somatic tinnitus (ST), otic tinnitus with somatic modulation (OT+) and otic tinnitus without somatic modulation (OT–), and to examine differences in somatic modulation between patients with ST and OT+. Methods: We retrospectively reviewed the medical records of 65 patients with unilateral tinnitus and classified the patients into three groups: ST (n = 24), OT+ (n = 21) and OT– (n = 20). Results: Only one difference in clinical characteristics was found between the OT+ and OT– groups. Maneuvers related to the temporomandibular joint showed the highest frequency of somatic modulation in both the ST and OT+ groups. There was no significant difference between the ST and OT+ groups with regard to the rate of somatic modulation or the rate of increase or decrease of tinnitus among all aspects of somatic testing. Conclusions: The presence or absence of somatic modulation does not influence the clinical characteristics of otic tinnitus, and the somatosensory-auditory interaction is a general auditory physiologic phenomenon.

Axonal topology influences the somatic modulation of synaptic output

Axonal topology influences the somatic modulation of synaptic output

M1299 Endogenous Pain Modulation and Brain Activity in Irritable Bowel Syndrome (IBS) and in Healthy Controls: Individual Correlations During FMRI

INTRODUCTION: A majority of patients with IBS show abnormal visceral and somatic sensory function and endogenous pain modulation compared to controls (Wilder-Smith C et al. World J Gastro 2007). While pain inhibition is evident in over 90% of controls, over 50% of IBS patients show pain facilitation and most of the remainder have decreased pain inhibition during heterotopic stimulation for activation of pain modulation. METHODS & AIMS: In this study we correlated individual pain intensities with individual fMRI brain activations in 14 female IBS (7 IBS-D, 7 IBS-C) and 14 female healthy subjects using electrical hand pain (pain threshold+20%) and foot cold pain (4°C) applied either alone or together (heterotopic stimulation). Hand stimulation below perception threshold was applied for control purposes. Six imaging runs (6x30s stimulation blocks) were presented in randomized sequence. Group-level activation maps using random effects general linear model with conditions of interest were generated via the finite impulse response (FIR) deconvolution method and corrected using cluster threshold estimation. RESULTS: After correction for multiple testing, there was a correlation in the change in hand pain during heterotopic stimulation and brain activation in the left anterior cingulate cortex ACC (BA 24), right ACC (BA32), right anterior insula and the right dorsolateral prefrontal cortex (BA9) during subliminal stimulation (p 0.60) in controls, but not in IBS. In IBS, but not controls, hand pain during endogenous painmodulation correlatedwith the changes in brain activation in the right ACC (BA32), left ACC (BA24) and PAG during heterotopic stimulation (p 0.55). If all subject data were pooled, individual pain ratings and brain activations correlated in the rostral ventromedial medulla, PAG, left and right amygdale, left putamen, right dorsolateral prefrontal cortex and the right precentral gyrus. CONCLUSIONS: Individual correlations of pain ratings and brain activations within the homeostatic modulatory network show significant differences between healthy and IBS subjects, both during subliminal stimulation and activation of endogenous pain modulation. There is consistent evidence for a shift in the dynamic balance between inhibition and facilitation.

102 Both Visceral and Somatic Endogenous Pain Modulation Is Abnormal in IBS Patients: A Meta-Analysis Across Different Races

102 Both Visceral and Somatic Endogenous Pain Modulation Is Abnormal in IBS Patients: A Meta-Analysis Across Different Races

Identifying tinnitus subgroups with cluster analysis.

We believe it is important to uncover tinnitus subgroups to identify subsets of patients most likely to benefit from different treatments. We review strategies for subgrouping based on etiology, subjective reports, the audiogram, psychoacoustics, imaging, and cluster analysis. Preliminary results of a 2-step cluster analysis based on 246 participants from whom we had 26 categorical and 25 continuous variables were determined. A 4-cluster solution suggested the following subgroups: (a) constant distressing tinnitus, (b) varying tinnitus that is worse in noise, (c) tinnitus patients who are copers and whose tinnitus is not influenced by touch (somatic modulation), and (d) tinnitus patients who are copers but whose tinnitus is worse in quiet environments. Subgroups of tinnitus patients can be identified by using statistical approaches. The subgroups we identify here represent a preliminary attempt at identifying such patients. One next step would be to explore clinical trials of tinnitus treatments based on subgroup analyses or on using subgroups in the selection criteria.

S1820 Somatic Afferent Modulation of Thoracic (T9-T10) Spinal Neurons Receiving Gastric Mechanical Input in Rats

S1820 Somatic Afferent Modulation of Thoracic (T9-T10) Spinal Neurons Receiving Gastric Mechanical Input in Rats

Somatic Modulation of Tinnitus: Test Reliability and Results after Repetitive Muscle Contraction Training

We sought to study the reliability of tinnitus modulation by muscle contractions and to observe the effect of their prolonged repetition. Thirty-eight patients with tinnitus underwent 9 maneuvers of muscle contractions in test and retest situations. After a 2-month training period of repeating the maneuvers, tinnitus modulation and daily perception were evaluated. There was no difference between the occurrence of tinnitus modulation in test (57.9%) and retest (63.2%) situations. After 2 months, the occurrence of modulation during the maneuvers was similar (55.3%), but a new pattern showed an increase in tinnitus improvement and a decrease in tinnitus worsening. The daily perception of tinnitus was unchanged. Maneuvers of head and neck muscle contractions evoked tinnitus modulation in a frequent and reliable manner. Also, the repetition of such maneuvers for 2 months altered the pattern of modulation.