Development of a novel brief quantitative sensory testing protocol that integrates static and dynamic pain assessments: Test-retest performance in healthy adults

Objective Quantitative sensory testing is an expanding pain research domain with numerous clinical and research applications. There is a recognized need for brief reliable quantitative sensory testing protocols that enhance assessment feasibility. This study aimed to integrate static (pain threshold, tolerance, suprathreshold) and dynamic (conditioned pain modulation, offset analgesia, temporal summation) pain reactivity measures into a brief 20-minute protocol that uses a single portable device. The test-retest performance of this optimized protocol was evaluated. Design Using a test-retest design, the brief quantitative sensory testing assessment was administered to participants on two occasions separated by exactly 7 days. Setting A clinical psychology research laboratory at Syracuse University. Subjects Participants were 33 healthy adults recruited from Syracuse University’s online research participation pool. Methods A portable computerized quantitative sensory testing device delivered contact-heat pain to assess static and dynamic pain measures in participants. Dynamic responses were continuously recorded using a computerized visual analog scale. Results Pain threshold, tolerance, and suprathreshold exhibited excellent reliability (intraclass correlations ranged from 0.80 to 0.83). Conditioned pain modulation, offset analgesia, temporal summation yielded reliability in the good to excellent range (intraclass correlations ranged from 0.66 to 0.71). Conclusions Findings suggested that this brief integrated QST protocol may reliably monitor human pain reactivity over brief periods. This protocol may enhance quantitative sensory testing feasibility in clinical and research settings.

Is Developmental Dyslexia Due to a Visual and Not a Phonological Impairment?

It is a widely held belief that developmental dyslexia (DD) is a phonological disorder in which readers have difficulty associating graphemes with their corresponding phonemes. In contrast, the magnocellular theory of dyslexia assumes that DD is a visual disorder caused by dysfunctional magnocellular neural pathways. The review explores arguments for and against these theories. Recent results have shown that DD is caused by (1) a reduced ability to simultaneously recognize sequences of letters that make up words, (2) longer fixation times required to simultaneously recognize strings of letters, and (3) amplitudes of saccades that do not match the number of simultaneously recognized letters. It was shown that pseudowords that could not be recognized simultaneously were recognized almost without errors when the fixation time was extended. However, there is an individual maximum number of letters that each reader with DD can recognize simultaneously. Findings on the neurobiological basis of temporal summation have shown that a necessary prolongation of fixation times is due to impaired processing mechanisms of the visual system, presumably involving magnocells and parvocells. An area in the mid-fusiform gyrus also appears to play a significant role in the ability to simultaneously recognize words and pseudowords. The results also contradict the assumption that DD is due to a lack of eye movement control. The present research does not support the assumption that DD is caused by a phonological disorder but shows that DD is due to a visual processing dysfunction.

Comparison of Thermal and Electrical Modalities in the Assessment of Temporal Summation of Pain and Conditioned Pain Modulation

Temporal summation of pain (TSP) and conditioned pain modulation (CPM) can be measured using a thermode and a cold pressor test (CPT). Unfortunately, these tools are complex, expensive, and are ill-suited for routine clinical assessments. Building on the results from an exploratory study that attempted to use transcutaneous electrical nerve stimulation (TENS) to measure CPM and TSP, the present study assesses whether a “new” TENS protocol can be used instead of the thermode and CPT to measure CPM and TSP. The objective of this study was to compare the thermode/CPT protocol with the new TENS protocol, by (1) measuring the association between the TSP evoked by the two protocols; (2) measuring the association between the CPM evoked by the two protocols; and by (3) assessing whether the two protocols successfully trigger TSP and CPM in a similar number of participants. We assessed TSP and CPM in 50 healthy participants, using our new TENS protocol and a thermode/CPT protocol (repeated measures and randomized order). In the TENS protocol, both the test stimulus (TS) and the conditioning stimulus (CS) were delivered using TENS; in the thermode/CPT protocol, the TS was delivered using a thermode and the CS consisted of a CPT. There was no association between the response evoked by the two protocols, neither for TSP nor for CPM. The number of participants showing TSP [49 with TENS and 29 with thermode (p < 0.001)] and CPM [16 with TENS and 30 with thermode (p = 0.01)] was different in both protocols. Our results suggest that response to one modality does not predict response to the other; as such, TENS cannot be used instead of a thermode/CPT protocol to assess TSP and CPM without significantly affecting the results. Moreover, while at first glance it appears that TENS is more effective than the thermode/CPT protocol to induce TSP, but less so to induce CPM, these results should be interpreted carefully. Indeed, TSP and CPM response appear to be modality-dependent as opposed to an absolute phenomenon, and the two protocols may tap into entirely different mechanisms, especially in the case of TSP.

Associations between joint pathologies and central sensitization in persons with hand osteoarthritis: results from the Nor-Hand study

Objective Pain sensitization is associated with pain severity in persons with hand OA. What contributes to pain sensitization is unclear. This study explores whether hand OA pathologies and symptom duration are related to central sensitization. Method Participants with hand OA in the Nor-Hand study underwent bilateral hand radiography and US examination. Central sensitization was assessed with pressure pain thresholds (PPT) at remote sites (wrist, trapezius and tibialis anterior muscles) and temporal summation. We examined whether hand OA pathologies, independent of each other, including structural severity (Kellgren–Lawrence sum score, presence of erosive hand OA), inflammatory severity (greyscale synovitis and power Doppler activity sum scores) and symptom duration, were related to central sensitization, adjusting for age, sex, BMI, comorbidities and OA-severity of knee/hip. Results In 291 participants (88% women, median age 61 years, interquartile range 57–66 years) Kellgren–Lawrence, greyscale synovitis and power Doppler activity sum scores were not associated with lower PPTs at remote sites. Persons with erosive hand OA had lower PPTs at the wrist (adjusted beta −0.75, 95% CI −1.32, −0.19) and tibialis anterior (adjusted beta −0.82, 95% CI −1.54, −0.09) and had greater temporal summation (adjusted beta 0.56, 95% CI 0.12, 1.01) compared with persons with non-erosive disease. No associations were found for symptom duration. Conclusions A person’s overall amount of structural or inflammatory hand OA pathologies was not associated with central sensitization. Although persons with erosive hand OA showed greater signs of central sensitization, the small differences suggest that central sensitization is mainly explained by factors other than joint pathologies.

The Temporal Pattern of Spiking Activity of a Thalamic Neuron are Related to the Amplitude of the Cortical Local Field Potential

Neuron activity in the sensory cortices mainly depends on feedforward thalamic inputs. High-frequency activity of a thalamic input can be temporally integrated by a neuron in the sensory cortex and is likely to induce larger depolarization. However, feedforward inhibition (FFI) and depression of excitatory synaptic transmission in thalamocortical pathways attenuate depolarization induced by the latter part of high-frequency spiking activity and the temporal summation may not be effective. The spiking activity of a thalamic neuron in a specific temporal pattern may circumvent FFI and depression of excitatory synapses. The present study determined the relationship between the temporal pattern of spiking activity of a single thalamic neuron and the degree of cortical activation as well as that between the firing rate of spiking activity of a single thalamic neuron and the degree of cortical activation. Spiking activity of a thalamic neuron was recorded extracellularly from the lateral geniculate nucleus (LGN) in male Long-Evans rats. Degree of cortical activation was assessed by simultaneous recording of local field potential (LFP) from the visual cortex. A specific temporal pattern appearing in three consecutive spikes of an LGN neuron induced larger cortical LFP modulation than high-frequency spiking activity during a short period. These findings indicate that spiking activity of thalamic inputs is integrated by a synaptic mechanism sensitive to an input temporal pattern.Significance StatementSensory cortical activity depends on thalamic inputs. Despite the importance of thalamocortical transmission, how spiking activity of thalamic inputs is integrated by cortical neurons remains unclear. Feedforward inhibition and synaptic depression of excitatory transmission may not allow simple temporal summation of membrane potential induced by consecutive spiking activity of a thalamic neuron. A specific temporal pattern appearing in three consecutive spikes of a thalamic neuron induced larger cortical local field potential modulation than high-frequency spiking activity during a short period. The findings indicate the importance of the temporal pattern of spiking activity of a single thalamic neuron on cortical activation.

Spinal cord neural activity of patients with fibromyalgia and healthy controls during temporal summation of pain: an fMRI study

“Windup” and its behavioral correlate “temporal-summation-of-second pain” (TSSP) represent spinal cord mechanisms of pain augmentation associated with central sensitization and chronic pain. Fibromyalgia (FM) is a chronic pain disorder, where abnormal TSSP has been demonstrated. We used fMRI to study spinal cord and brainstem activation during TSSP. We characterized the time course of spinal cord and brainstem BOLD activity during TSSP which showed abnormal brainstem activity in patients with FM, possibly due to deficient pain modulation.

Psychophysical predictors of experimental muscle pain intensity following fatiguing calf exercise

Musculoskeletal pain affects approximately 20% of the population worldwide and represents one of the leading causes of global disability. As yet, precise mechanisms underlying the development of musculoskeletal pain and transition to chronicity remain unclear, though individual factors such as sleep quality, physical activity, affective state, pain catastrophizing and psychophysical pain sensitivity have all been suggested to be involved. This study aimed to investigate whether factors at baseline could predict musculoskeletal pain intensity to an experimental delayed onset of muscle soreness (DOMS) pain model. Demographics, physical activity, pain catastrophizing, affective state, sleep quality, isometric force production, temporal summation of pain, and psychophysical pain sensitivity using handheld and cuff algometry were assessed at baseline (Day-0) and two days after (Day-2) in 28 healthy participants. DOMS was induced on Day-0 by completing eccentric calf raises on the non-dominant leg to fatigue. On Day-2, participants rated pain on muscle contraction (visual analogue scale, VAS, 0-10cm) and function (Likert scale, 0–6). DOMS resulted in non-dominant calf pain at Day-2 (3.0±2.3cm), with significantly reduced isometric force production (P<0.043) and handheld pressure pain thresholds (P<0.010) at Day-2 compared to Day-0. Linear regression models using backward selection predicted from 39.3% (P<0.003) of VAS to 57.7% (P<0.001) of Likert score variation in DOMS pain intensity and consistently included cuff pressure pain tolerance threshold (P<0.01), temporal summation of pain (P<0.04), and age (P<0.02) as independent predictive factors. The findings indicate that age, psychological and central pain mechanistic factors are consistently associated with pain following acute muscle injury.