Quantitative Sensory Testing to Predict Postoperative Pain.

PURPOSE OF REVIEW: We review the relevance of quantitative sensory testing (QST) in light of acute and chronic postoperative pain and associated challenges. RECENT FINDINGS: Predicting the occurrence of acute and chronic postoperative pain with QST can help identify patients at risk and allows proactive preventive management. Generally, central QST testing, such as temporal summation of pain (TSP) and conditioned pain modulation (CPM), appear to be the most promising modalities for reliable prediction of postoperative pain by QST. Overall, QST testing has the best predictive value in patients undergoing orthopedic procedures. Current evidence underlines the potential of preoperative QST to predict postoperative pain in patients undergoing elective surgery. Implementing QST in routine preoperative screening can help advancing traditional pain therapy toward personalized perioperative pain medicine.

The relation of peripheral and central sensitization to muscle co-contraction: the MOST study.

OBJECTIVE: To examine the relation of pain sensitization to altered motor activity in knee OA as assessed by hamstrings muscle co-contraction during maximal effort knee extension. DESIGN: Medial, lateral, and overall hamstring co-contraction was assessed in the Multicenter Osteoarthritis (MOST) Study cohort using electromyography during isokinetic knee extension at 60°/second. Mechanical temporal summation of pain (TS) was assessed at the right wrist and pressure pain thresholds (PPT) were assessed at the patellae; PPTs were categorized into sex-specific tertiles. Muscle co-contraction was categorized into age- and sex-specific tertiles. We evaluated the relation of measures of sensitization to muscle co-contraction using a generalized logistic regression model. RESULTS: 1633 participants were included: mean age and BMI was 67.3 ± 7.7 years and 30.3 ± 5.6 kg/m2, respectively; 58% were female. Presence of TS was associated with higher overall (OR 1.3, 95% confidence interval (CI) (1.0-1.8)), medial (1.4 (1.0-1.9), and lateral (1.3 (1.0, 1.9)) hamstring co-contraction. The lowest PPT tertile (greater sensitivity) was associated with higher overall (1.5 (1.0, 2.3)) and medial (1.5 (1.0, 2.3)) hamstring co-contraction compared with those in the highest PPT tertile. CONCLUSION: Greater pain sensitization, as assessed by presence of TS at the wrist and low patellar PPT, was associated with greater overall and medial hamstring co-contraction during knee extension. This provides support to the possibility that peripheral and/or central nervous system alterations may not only affect pain sensitivity, but also motor function.

Childhood Adversity and Pain Facilitation.

OBJECTIVE: This study investigated whether childhood adversity would be associated with hypersensitivity on two measures of central pain facilitation: area of secondary allodynia and temporal summation of second pain (TSSP), and whether pain facilitation would be explained by adult posttraumatic stress disorder (PTSD) symptoms. METHOD: Participants endorsing high (n = 31) and low (n = 31) childhood adversity underwent capsaicin-induced secondary allodynia and TSSP testing. The tests were conducted a week apart with test order counterbalanced. RESULTS: Larger areas of secondary allodynia were observed in the high adversity group compared with the low adversity group (F(1,60) = 4.81, p = .032). This group difference was largely (62%) explained by greater PTSD symptoms in the high adversity group. Although no overall difference was found in TSSP slopes (p = .886), this was attributed to an order by group interaction (F(1,58) = 5.07, p = .028) and low power. Subsequent analyses revealed positive TSSP slopes in the high adversity group when TSSP testing was performed first, and this order effect was associated with blunted sympathetic responses to TSSP on the first visit. The two facilitation measures were unrelated (p = .631). CONCLUSIONS: Larger areas of secondary allodynia were observed in the high adversity group, which was explained largely by PTSD symptoms. This suggests that adversity-related changes in pain facilitation may underlie the association between childhood adversity and generalized widespread pain. Although TSSP was affected by previous testing, adversity-related pain facilitation was observed when TSSP testing occurred first. Finally, adversity was not associated with a consistent pattern of hypersensitivity across the two measures of central pain facilitation.

A neural circuit for spatial summation in visual cortex.

The response of cortical neurons to a sensory stimulus is modulated by the context. In the visual cortex, for example, stimulation of a pyramidal cell's receptive-field surround can attenuate the cell's response to a stimulus in the centre of its receptive field, a phenomenon called surround suppression. Whether cortical circuits contribute to surround suppression or whether the phenomenon is entirely relayed from earlier stages of visual processing is debated. Here we show that, in contrast to pyramidal cells, the response of somatostatin-expressing inhibitory neurons (SOMs) in the superficial layers of the mouse visual cortex increases with stimulation of the receptive-field surround. This difference results from the preferential excitation of SOMs by horizontal cortical axons. By perturbing the activity of SOMs, we show that these neurons contribute to pyramidal cells' surround suppression. These results establish a cortical circuit for surround suppression and attribute a particular function to a genetically defined type of inhibitory neuron.

Association Between Borderline Personality Features and Temporal Summation of Second Pain: A Cross-Sectional Study.

Individuals with greater borderline personality features may be vulnerable to chronic pain. Because pain is an unpleasant sensory and emotional experience, affect dysregulation as the core personality feature may be linked to pain hypersensitivity. Studies have found that greater borderline features are associated with increased intensity in clinical and experimental pain, and that depression mediates this increase. The current study further examined the association between borderline features and heat pain sensitivity, the contribution of affect dysregulation and the other borderline personality factors (identity problems, negative relationships, self-harming/impulsivity) to the association, and depression as a mediator. Additionally, we examined whether blunted sympathetic responses mediate the association between borderline features and temporal summation of second pain (TSSP). Thermal pain threshold, thermal TSSP and aftersensations pain were assessed in 79 healthy individuals with varying degrees of borderline features. TSSP is a proxy measure for central sensitization and refers to the gradual increase in pain to repeated nociceptive stimuli. A regression analysis showed that greater borderline features predicted greater TSSP (ß = .22, p = .050, R2 = .05). Borderline features were unrelated to pain threshold and TSSP decay. A stepwise regression showed greater TSSP in individuals with greater borderline features was accounted for by the negative relationships factor rather than the affect dysregulation factor. The results of mediational analyses showed depression and blunted sympathetic skin conductance responses mediated the positive association between TSSP and borderline features.

[Loudness optimized registration of compound action potential in cochlear implant recipients]. / Lautheitsoptimierte Messung von Summenaktionspotentialen bei Cochlea Implantat Trägern.

Background Postoperative measurements of compound action potentials are not always possible due to the insufficient acceptance of the CI-recipients. This study investigated the impact of different parameters on the acceptance of the measurements. Methods Compound action potentials of 16 CI recipients were measured with different pulse-widths. Recipients performed a loudness rating at the potential thresholds with the different sequences. Results Compound action potentials obtained with higher pulse-widths were rated softer than those obtained with smaller pulse-widths. Conclusions Compound action potentials measured with higher pulse-widths generate a gap between loudest acceptable presentation level and potential threshold. This gap contributes to a higher acceptance of postoperative measurements.

Sensitivity and sensitisation in relation to pain severity in knee osteoarthritis: trait or state?

OBJECTIVES: It is not clear whether heightened pain sensitivity in knee osteoarthritis (OA) is related to sensitisation induced by nociceptive input from OA pathology ('state') versus other confounding factors. Conversely, some individuals may be predisposed to sensitisation irrespective of OA ('trait'). METHODS: The Multicenter Osteoarthritis Study is a longitudinal cohort of persons with or at risk of knee OA. We obtained knee X-rays, pain questionnaires and comprehensive assessment of factors that can influence pain sensitivity. We examined the relation of sensitisation and sensitivity assessed by mechanical temporal summation (TS) and pressure pain thresholds (PPTs) to knee OA and knee pain severity. To test whether sensitisation and sensitivity is a 'state' induced by OA pathology, we examined the relation of PPT and TS to knee OA duration and severity. RESULTS: In 2126 subjects (mean age 68, mean body mass index (BMI) 31, 61% female), PPT and TS were not associated with radiographic OA (ORs 0.9-1.0 for PPT and TS; p>0.05). However, PPT and TS were associated with pain severity (ORs: 1.7-2.0 for PPT; 1.3-1.6 for TS; p<0.05). Knee OA duration and radiographic severity were not associated with PPT or TS. CONCLUSIONS: PPT and TS were associated with OA-related pain, but not radiographic OA after accounting for pertinent confounders in this large cohort. Lack of association with disease duration suggests at least some sensitisation and pain sensitivity may be a trait rather than state. Understanding the relationship between pathological pain and pain sensitivity/sensitisation offers insight into OA pain risk factors and pain management opportunities.

Area summation of first- and second-order modulations of luminance.

To extend our understanding of the early visual hierarchy, we investigated the long-range integration of first- and second-order signals in spatial vision. In our first experiment we performed a conventional area summation experiment where we varied the diameter of (a) luminance-modulated (LM) noise and (b) contrast-modulated (CM) noise. Results from the LM condition replicated previous findings with sine-wave gratings in the absence of noise, consistent with long-range integration of signal contrast over space. For CM, the summation function was much shallower than for LM suggesting, at first glance, that the signal integration process was spatially less extensive than for LM. However, an alternative possibility was that the high spatial frequency noise carrier for the CM signal was attenuated by peripheral retina (or cortex), thereby impeding our ability to observe area summation of CM in the conventional way. To test this, we developed the "Swiss cheese" stimulus of Meese and Summers (2007) in which signal area can be varied without changing the stimulus diameter, providing some protection against inhomogeneity of the retinal field. Using this technique and a two-component subthreshold summation paradigm we found that (a) CM is spatially integrated over at least five stimulus cycles (possibly more), (b) spatial integration follows square-law signal transduction for both LM and CM and (c) the summing device integrates over spatially-interdigitated LM and CM signals when they are co-oriented, but not when cross-oriented. The spatial pooling mechanism that we have identified would be a good candidate component for a module involved in representing visual textures, including their spatial extent.

Fourth-root summation of contrast over area: No end in sight when spatially inhomogeneous sensitivity is compensated by a witch's hat.

Measurements of area summation for luminance-modulated stimuli are typically confounded by variations in sensitivity across the retina. Recently we conducted a detailed analysis of sensitivity across the visual field (Baldwin, Meese, & Baker, 2012) and found it to be well described by a bilinear "witch's hat" function: Sensitivity declines rapidly over the first eight cycles or so, but more gently thereafter. Here we multiplied luminance-modulated stimuli (4 cycles/degree gratings and "Swiss cheeses") by the inverse of the witch's hat function to compensate for the inhomogeneity. This revealed summation functions that were straight lines (on double log axes) with a slope of -1/4 extending to ≥33 cycles, demonstrating fourth-root summation of contrast over a wider area than has previously been reported for the central retina. Fourth-root summation is typically attributed to probability summation, but recent studies have rejected that interpretation in favor of a noisy energy model that performs local square-law transduction of the signal, adds noise at each location of the target, and then sums over signal area. Modeling shows our results to be consistent with a wide field application of such a contrast integrator. We reject a probability summation model, a quadratic model, and a matched template model of our results under the assumptions of signal detection theory. We also reject the high threshold theory of contrast detection under the assumption of probability summation over area.

Postsynaptic Potentiation in Mouse Motor Synapses Induced by ATP Accumulation in Synaptic Cleft.

In mouse motor synapses, a non-selective purinoceptor antagonist suramin increased the quantum content of endplate potentials (EPP) without changing the time course of synaptic potentials. An ectonucleotidase inhibitor ARL 67156 had no effect on the amplitude and quantum content of EPP and miniature endplate potentials (mEPP) evoked by single stimuli, but significantly prolonged their duration. Long-term high-frequency stimulation of the nerve in the presence of ARL 67156 persistently increased the amplitude and duration of EPP during the train of impulses, but did not change their quantum content. ATP-γ-S, a non-hydrolyzed ATP analogue, significantly increased the amplitudes and prolonged the rising and falling phases of EPP and mEPP. The ATP-induced postsynaptic potentiation in neuromuscular transmission can result from the increase in ATP content and its longer presence in the synaptic cleft.

Directional summation in non-direction selective retinal ganglion cells.

Retinal ganglion cells receive inputs from multiple bipolar cells which must be integrated before a decision to fire is made. Theoretical studies have provided clues about how this integration is accomplished but have not directly determined the rules regulating summation of closely timed inputs along single or multiple dendrites. Here we have examined dendritic summation of multiple inputs along On ganglion cell dendrites in whole mount rat retina. We activated inputs at targeted locations by uncaging glutamate sequentially to generate apparent motion along On ganglion cell dendrites in whole mount retina. Summation was directional and dependent13 on input sequence. Input moving away from the soma (centrifugal) resulted in supralinear summation, while activation sequences moving toward the soma (centripetal) were linear. Enhanced summation for centrifugal activation was robust as it was also observed in cultured retinal ganglion cells. This directional summation was dependent on hyperpolarization activated cyclic nucleotide-gated (HCN) channels as blockade with ZD7288 eliminated directionality. A computational model confirms that activation of HCN channels can override a preference for centripetal summation expected from cell anatomy. This type of direction selectivity could play a role in coding movement similar to the axial selectivity seen in locust ganglion cells which detect looming stimuli. More generally, these results suggest that non-directional retinal ganglion cells can discriminate between input sequences independent of the retina network.

Isometric exercise as a test of pain modulation: effects of experimental pain test, psychological variables, and sex.

OBJECTIVE: Little is known regarding whether exercise-induced hypoalgesia (EIH) produced by isometric exercise is influenced by psychological factors or systematically varies across multiple experimental psychophysical pain tests. Thus, this study sought to determine the influence of experimental pain test, psychological factors, and sex on the hypoalgesic response of submaximal isometric exercise. METHODS: Healthy young males (N = 12) and females (N = 15) completed one training and two testing sessions consisting of quiet rest (control condition) or a 3-minute isometric handgrip performed at 25% of maximum voluntary contraction. Pain testing was conducted on both forearms prior to and following exercise and quiet rest. The pain tests included: pressure pain thresholds (PPT), suprathreshold pressure pain test, static prolonged heat test, and temporal summation of heat pain. Participants completed the Pain Catastrophizing Scale during the training session and the State-Trait Anxiety Inventory-State version prior to each session. The data were analyzed with mixed model analyses of variance, partial Pearson correlations, and hierarchical regression analyses. RESULTS: Isometric exercise increased PPTs for men and women, reduced pain perception during static prolonged heat stimuli for women, and reduced temporal summation of pain for men and women. Greater pain catastrophizing was associated with smaller reductions in temporal summation following isometric exercise. CONCLUSIONS: These findings demonstrate that the hypoalgesic response to submaximal isometric exercise is partially a function of sex and experimental pain test. Furthermore, the relationship between EIH and pain catastrophizing was psychophysical pain test specific, with greater pain catastrophizing predicting diminished EIH only during the temporal summation of pain trials.

Chronic temporomandibular disorders are not necessarily associated with a compromised endogenous analgesic system.

AIMS: To test whether temporomandibular disorders (TMD) case-control differences in conditioned pain modulation (CPM) exist, using a mechanically evoked temporal summation (TS) model. METHODS: A series of 10 repetitive, mildly noxious, mechanical stimuli were applied to the fingers of 30 women with TMD, who had a primary diagnosis of masticatory myofascial pain, and 30 age-matched healthy women. The subjects rated the pain intensity caused by the 1st, 5th, and 10th stimuli in the series. To evaluate CPM, the same series of mechanical stimulations were applied with concomitant exposure of the other hand to a painfully cold water bath. Statistical inferences were based on t tests, chi-square tests, or analysis of variance (ANOVA), as appropriate. RESULTS: Pain ratings increased significantly with stimulus repetition (P < .01) and CPM significantly reduced TS of pain (P < .01). Of particular note, both groups showed very similar degrees of CPM, with no significant group difference. CONCLUSION: Painful TMD is not necessarily associated with a compromised ability to engage the endogenous analgesic system in an experimental setting.

[Temporal summation in masking and speech recognition].

Temporal summation in masking has been measured simultaneously with a resolution of the masker's spectral structure to find psychoacoustic characteristics for estimation of speech intelligibility, to detect the manifestation of peripheral processes in auditory perception in humans. For this, detection thresholds of a test signal with different durations were determined. The test signal was pulse with a Gaussian envelope and a sine-wave carrier. It was presented simultaneously with a noise masker. The minimal pulse duration was inversely proportional to width of the critical bands of hearing, formed at the pulse's center frequency. The maximal pulse duration always was 50 ms. We adopted pulses with duration of 1-10 ms as a model of consonants and pulses with duration of 20-50 ms as a model of vowels. The band pass noises with rippled structure of the amplitude spectrum of two types were used as maskers. The central frequency of one masker coincided with a spectral hump and the central frequency of the other--with the spectral failure. If the pulses and maskers central frequencies were equal, the first and second maskers were called on- and - off- maskers. If the auditory system could discriminate the rippled structure of the masker's spectra, the difference in the detection thresholds of the pulses, which was presented with each of the maskers, was not equal to zero. The difference in the detection thresholds allows us to estimate resolution of the masker's spectra, i.e. frequency selectivity. Changes in the pulse's and masker's central frequencies allow us to evaluate the hearing ability in certain frequency domain. Changes in the masker's levels allow us to find influence of nonlinear dynamic properties of cochlea on temporal summation and frequency selectivity. This paper presents the results of measurements of temporal summation in masking, obtained in two frequency domains 2 and 4 kHz, in 4 subjects with normal hearing and in 1 subject with age-related hearing loss, who complained about deterioration of speech intelligibility. It has been found an increasing temporal summation and an improving the resolution of the rippled structure of the amplitude spectra for the maskers with average levels. We believe, the reasons could be found in the properties of the peripheral pulse coding, such as (1) the stabilization zones of excitation of the basilar.membrane, the range of the characteristic frequencies and the number of excited auditory nerve fibers and the number ofspikes, generated by fibers, due to the nonlinearity of the dynamic properties of the cochlea, (2) increasing synchronization of a reaction of the excited fibers and shortening in time of this reaction, due to thefiber's refractory properties.

Lack of temporal summation but distinct aftersensations to thermal stimulation in patients with combined tension-type headache and myofascial temporomandibular disorder.

AIMS: To compare patients with combined tension-type headache and myofascial temporomandibular disorder (TMD) with control subjects on two measures of central processing-ie, temporal summation and aftersensations to heat stimulation in the trigeminal nerve and spinal nerve territories. METHODS: A novel heat stimulation protocol was used in which 13 females with tension-type headache/TMD and 20 female controls were exposed to 11 painful heat stimuli at a rate of 0.33 Hz. Two temperature ranges (low, 44°C to 46°C; high, 45°C to 47°C) were tested on the cheek and arm in separate trials. Perceived pain was rated on a 100-mm visual analog scale after the second, sixth, and eleventh stimulus presentation and every 15 seconds after the final stimulus presentation (aftersensations) for up to 3 minutes. The duration of aftersensations was compared using the student unpaired t test with Welch correction. RESULTS: Temporal summation was not observed in any of the groups, but aftersensations were consistently reported. The aftersensations lasted longer in tension-type headache/TMD patients (right cheek, 100.4 ± 62.0 seconds; right arm, 115.4 ± 64.0 seconds) than in controls (right cheek, 19.5 ± 2.5 seconds; right arm, 20.3 ± 2.7 seconds) (P < .05). A cutoff value (right cheek, 44.6 seconds; right arm, 41.5 seconds) provided a sensitivity and specificity of 0.77 and 0.95, respectively, with the high stimulus protocol. CONCLUSION: The results from this pilot study suggest that aftersensations to painful heat stimulation can appear without temporal summation. Furthermore, the developed test protocol has a good predictive value and may have the potential to discriminate between tension-type headache/TMD patients and control subjects.

Pattern of summation with fatigue and inhibition of calcium release in rat muscle.

INTRODUCTION: Fatigue disrupts muscle force summation and is associated with a decrease in cytoplasmic Ca(2+) concentration. The purpose of this study was to compare summation during fatigue and recovery with summation during dantrolene-induced inhibition of Ca(2+) release. METHODS: Rat medial gastrocnemius muscles were evaluated before and after fatigue, or during exposure to dantrolene. Summation was quantified by the ratio of the force transient associated with the final activation in a train of stimuli (Twf), obtained by subtraction of the force with one less stimulus, and the force of the twitch (Tw). RESULTS: This ratio (Twf/Tw) decreased from 2.46 ± 0.11 (mean ± SEM) to 0.8 ± 0.1 during intermittent contractions, but was still significantly different from non-fatigued muscle after 10 min of recovery. Dantrolene altered summation, as Twf/Tw was 1.7 ± 0.2 and 1.27 ± 0.15 at a low dose and a high dose, respectively. CONCLUSIONS: Inhibition of Ca(2+) release alters summation, but repetitive stimulation leading to fatigue changes it more substantially.

Stereoscopic depth adaptation from binocularly correlated versus anti-correlated noise: Test of an efficient coding theory of stereopsis.

Stereoscopic, or "3D" vision in humans is mediated by neurons sensitive to the disparities in the positions of objects in the two eyes' views. A disparity-sensitive neuron is typically characterized by its responses to left- and right-eye monocular signals, SL and SR, respectively. However, it can alternatively be characterized by sensitivity to the sum of the two eyes' inputs, S+ = SL + SR, and the difference, S- = SL - SR. Li and Atick's theory of efficient binocular encoding proposes that the S+ and S- signals can be separately weighted to maximize the efficiency with which binocular information is encoded. This adaptation changes each neuron's sensitivity and preferred binocular disparity, resulting in predicted effects on the perceived stereoscopic depth of objects. To test these predictions, we measured the apparent depth of a random-dot stereogram with an 'in-front' target following adaptation to binocularly correlated or anti-correlated horizontally-oriented grating stimuli, which reduce sensitivity to the S+ and S- signals, respectively, but which contain no conventional stereo-depth signals. The anti-correlated noise adaptation made the target appear relatively closer to the background than the correlated noise adaptation, with differences of up to 60%. We show how this finding can be accommodated by a standard model of binocular disparity processing, modified to incorporate the binocular adaptation suggested by Li and Atick's theory.

Dependence of the filled-space illusion on the size and location of contextual distractors.

For most observers, the part of the stimulus that is filled with some visual elements (e.g., distractors) appears larger than the unfilled part of the same size. This illusion of interrupted spatial extent is also known as the \'filled­space' or 'Oppel­Kundt' illusion. Although the continuously filled­space illusion has been systematically studied for over a century, there is still no generally accepted explanation of its origin. The present study aimed to further develop our computational model of the continuously filled­space illusion and to examine whether the model predictions successfully account for illusory effects caused by distracting line­segments of various lengths that are\r\nattached to different endpoints (i.e., terminators) of the reference spatial interval of the three­dot stimulus. Our experiments confirm that the illusion manifests itself along a distracting segment located both inside and outside of the reference interval. In the case of two distractors arranged symmetrically with respect to the lateral terminator, we found that the magnitude of the illusion is approximately equal to the sum of the relevant values obtained with separate distractors. The results of experiments using vertical shifts of distractors supported the model's assumption regarding the two­dimensional Gaussian profile of hypothetical areas of weighted spatial summation\r\nof neural activity. A good correspondence between the experimental and theoretical results supports the suggestion that perceptual positional biases associated with the context­evoked increase in neural excitation may be one of the main causes of the continuously filled­space illusion.

Assessing peripheral fibers, pain sensitivity, central sensitization, and descending inhibition in Native Americans: main findings from the Oklahoma Study of Native American Pain Risk.

Native Americans (NAs) have a higher prevalence of chronic pain than other U.S. racial/ethnic groups, but there have been few attempts to understand the mechanisms of this pain disparity. This study used a comprehensive battery of laboratory tasks to assess peripheral fiber function (cool/warm detection thresholds), pain sensitivity (eg, thresholds/tolerances), central sensitization (eg, temporal summation), and pain inhibition (conditioned pain modulation) in healthy, pain-free adults (N = 155 NAs, N = 150 non-Hispanic Whites [NHWs]). Multiple pain stimulus modalities were used (eg, cold, heat, pressure, ischemic, and electric), and subjective (eg, pain ratings and pain tolerance) and physiological (eg, nociceptive flexion reflex) outcomes were measured. There were no group differences on any measure, except that NAs had lower cold-pressor pain thresholds and tolerances, indicating greater pain sensitivity than NHWs. These findings suggest that there are no group differences between healthy NAs and NHWs on peripheral fiber function, central sensitization, or central pain inhibition, but NAs may have greater sensitivity to cold pain. Future studies are needed to examine potential within-group factors that might contribute to NA pain risk.