Temporal summation does not predict the acupuncture response in patients with chronic non-specific low back pain.

Introduction: Previously, we had observed that immediate pain reduction after one acupuncture treatment was associated with high temporal summation of pain (TS) at a pain free control site and younger age in a mixed population of chronic pain patients. The aim of the present study was to verify these results in chronic non-specific low back pain (LBP) and to collect pilot data on the association between TS and the response to an acupuncture series. Methods: TS at a pain free control site (back of dominant hand) and at the pain site was quantified by the pin-prick induced wind-up ratio (WUR) in 60 LBP patients aged 50 years or younger. Response to one acupuncture treatment was assessed by change in pain intensity and pressure pain threshold (PPT) at the pain site. The primary hypothesis was that a high TS (WUR > 2.5) would be associated with a clinically relevant reduction in pain intensity of at least 30%. In study part two, 26 patients received nine additional treatments. Response to the acupuncture series was assessed by the pain intensity during the last week, the PPT and the Hannover functional ability questionnaire (FFbH-R). Results: An immediate reduction in pain intensity of at least 30% was frequent irrespective of TS at the control site (low vs. high TS 58% vs. 72%, p = 0.266). High TS at the pain site was also not significantly associated with a clinically relevant immediate reduction in pain intensity (low vs. high TS 46% vs. 73%, p = 0.064). The PPT was not changed after one acupuncture treatment. Study part two did not reveal a consistent association between TS at the control site and any of the outcome measures but also a trend toward a higher chance for a clinically relevant response along with low TS at the pain site. Conclusion: Our results do not suggest an important role of TS for predicting a clinically important acupuncture effect or the response to a series of 10 acupuncture treatments in patients with chronic non-specific LBP. Overall high response rates imply that acupuncture is a suitable treatment option for LBP patients irrespective of their TS.

A myriad of methods to determine temporal summation of pain in people with musculoskeletal pain and healthy participants: a scoping review.

Temporal summation of pain (TSP) is a human proxy for wind-up of dorsal horn neurons as assessed in animals. The common paradigm for eliciting TSP is evoked by repetitive nociceptive stimuli of equal intensity. Various stimulation and assessment protocols have been used. This scoping review aims to provide insight into key elements of TSP stimulation and assessment: modality, instruments, test location, familiarization, train characteristics, and calculations. PubMed, Embase, and Ebsco/CINAHL were searched for studies that measured TSP in adults with musculoskeletal conditions and healthy people. Four hundred six studies were included. Mechanical stimuli were the most commonly used modality (250 studies), followed by thermal stimuli (125 studies). Forty-six different instruments were used. Disregarding studies on widespread musculoskeletal pain and healthy participants, 40 studies evaluated TSP at painful sites, 77 in remote areas, and 66 in both locations. Of the 13 tested locations in patients, the hand (74 studies), lower leg (64 studies), and forearm (59 studies) were most commonly tested. A single practice round was the most common familiarization method (46 studies). Repeated stimuli were applied using 31 different frequencies (0.03-200 Hz) and sustained stimulations ranging from 5 to 1080 seconds were used. Twenty-two different train lengths, 63 different calculations (37 absolute, 19 relative, and 7 alternatives using data directly), and 14 different outcome measures (eg, self-reported pain rating scales and reflex thresholds) were used. Temporal summation of pain protocols vary excessively, hindering the comparison and pooling of results. None of the studies provided substantiation for their protocol choice.

Change in Endogenous Pain Modulation Depending on Emotional States in Healthy Subjects: A Randomized Controlled Trial.

INTRODUCTION: Chronic pain is a public health issue, leading to substantial healthcare costs and diminished quality of life for sufferers. While the role of anxiety in pain modulation has been extensively studied, the effects of other emotional states on the body's pain control mechanisms remain less understood. This study sought to explore how different emotions (happiness, anger, sadness, and interest) affect conditioned pain modulation (CPM) and the wind-up phenomenon in healthy adults. METHODS: This randomized controlled, cross-over trial involved 28 healthy participants aged 18-60. Participants watched video clips designed to induce specific emotions: happiness, anger, sadness, and interest. Emotional states were assessed using a 7-point Likert scale. Pain modulation was measured using CPM and the wind-up phenomenon. CPM was assessed with a hot water bath as the conditioning stimulus and pressure pain tolerance as the test stimulus. Wind-up was measured using pinprick needle stimulators and a visual analog scale. Data were analyzed using paired t tests to compare pre- and post-emotion induction values. RESULTS: Significant changes in emotional self-assessment values were observed for all emotions. Happiness increased CPM (4.6 ± 11.4, p = 0.04277), while sadness - 9.9 ± 23.1, p = 0.03211) and anger - 9.1 ± 23.3, p = 0.04804) decreased it. Interest did not significantly alter CPM (- 5.1 ± 25.8, p = 0.31042). No significant effects were found for the wind-up phenomenon across any emotional states. CONCLUSION: This study shows that emotional states significantly affect the body's ability to modulate pain. Positive emotions like happiness enhance pain inhibition, while negative emotions such as sadness and anger impair it. These findings suggest that emotional modulation techniques could be integrated into pain management strategies to improve patient outcomes. Further research should explore a broader range of emotions and include objective measures to validate these results.

Chronic pain is a widespread problem that affects millions of people and leads to high healthcare costs and decreased quality of life. Understanding how emotions impact pain can help us find better ways to manage it. This study looked at how different emotions (happiness, anger, sadness, and interest) affect the ability of the body to naturally control pain in healthy adults. Participants experienced different tests in a random order, like flipping a coin to decide the order. Each participant took part in all the tests to compare how different conditions affected them. We measured changes in their pain perception using two methods: conditioned pain modulation, which reflects how well the body can suppress pain after experiencing another painful stimulus, and the wind-up phenomenon, which measures how pain intensity increases with repeated stimulation. We found that emotions affected the body's ability to control pain. Sadness and anger reduced the efficacy of conditioned pain modulation, making it harder for the body to reduce pain. Happiness improved CPM, enhancing the body's natural ability to stop pain. Interest did not significantly change how pain was felt. We also did not find any significant changes in the wind-up phenomenon for any of the emotions tested. The results suggest that positive emotions like happiness can help reduce pain, while negative emotions like sadness and anger can make pain worse. This could lead to new pain management approaches that include methods to boost positive emotions and reduce negative ones.

Neuropathic pain in cats: Mechanisms and multimodal management.

PRACTICAL RELEVANCE: Chronic pain is a significant welfare concern in cats, and neuropathic pain, which arises from aberrant processing of sensory signals within the nervous system, is a subcategory of this type of pain. To comprehend this condition and how multimodal pharmacotherapy plays a central role in alleviating discomfort, it is crucial to delve into the anatomy of nociception and pain perception. In addition, there is an intricate interplay between emotional health and chronic pain in cats, and understanding and addressing the emotional factors that contribute to pain perception, and vice versa, is essential for comprehensive care.Clinical approach:Neuropathic pain is suspected if there is abnormal sensation in the area of the distribution of pain, together with a positive response to trial treatment with drugs effective for neuropathic pain. Ideally, this clinical suspicion would be supported by confirmation of a lesion at this neurolocalisation using diagnostic modalities such as MRI and neuroelectrophysiology. Alternatively, there may be a history of known trauma at that site. A variety of therapies, including analgesic, anti-inflammatory and adjuvant drugs, and neuromodulation (eg, TENS or acupuncture), can be employed to address different facets of pain pathways.Aim:This review article, aimed at primary care/ general practitioners, focuses on the identification and management of neuropathic pain in cats. Three case vignettes are included and a structured treatment algorithm is presented to guide veterinarians in tailoring interventions.Evidence base:The review draws on current literature, where available, along with the author's extensive experience and research.

Optimizing Temporal Summation of Heat Pain Using a Constant Contact Heat Stimulator.

Purpose: Temporal summation (TS) of pain occurs when pain increases over repeated presentations of identical noxious stimuli. TS paradigms can model central sensitization, a state of hyperexcitability in nociceptive pathways that promotes chronic pain onset and maintenance. Many experimenters use painful heat stimuli to measure TS (TS-heat); yet, TS-heat research faces unresolved challenges, including difficulty evoking summation in up to 30-50% of participants. Moreover, substantial variability exists between laboratories regarding the methods for evoking and calculating TS-heat. Patients and Methods: To address these limitations, this study sought to identify optimal parameters for evoking TS-heat in healthy participants with a commercially available constant contact heat stimulator, the Medoc TSA-II. Working within constraints of the TSA-II, stimulus trains with varying parameters (eg, stimulus frequency, baseline temp, peak temp, peak duration, testing site) were tested in a sample of 32 healthy, chronic pain-free participants to determine which combination best evoked TS-heat. To determine whether TS scoring method altered results, TS-heat was scored using three common methods. Results: Across all methods, only two trains successfully evoked group-level TS-heat. These trains shared the following parameters: site (palmar hand), baseline and peak temperatures (44°C and 50°C, respectively), and peak duration (0.5 s). Both produced summation that peaked at moderate pain (~50 out of 100 rating). Conclusion: Future TS-heat investigations using constant contact thermodes and fixed protocols may benefit from adopting stimulus parameters that include testing on the palmar hand, using 44°C baseline and 50°C peak temperatures, at ≥0.33 Hz stimulus frequency, and peak pulse durations of at least 0.5 seconds.

The association between mechanical temporal summation, state anxiety at baseline, and persistent low back pain: a 12-month prospective cohort study.

BACKGROUND: Persons with acute low back pain (LBP) have a good prognosis for regaining function, while pain often persists. Neurobiological and psychosocial factors are recognized to amplify pain responses, as reported for central sensitization. This study investigated the combination of mechanical temporal summation (TS) chosen to characterize central sensitization and state anxiety representing a psychological factor and their association with persistent pain. METHODS: A longitudinal prospective cohort study including 176 participants aged between 18 and 65 with acute LBP was performed. The following independent variables were analyzed at baseline: The mechanical TS at the lower back, of whom the Wind-up ratio (WUR) was calculated, and the state anxiety level measured with the State and Trait Anxiety Inventory (STAI-S). The outcome pain intensity was assessed at baseline and 2,3,6 and 12 months after the onset of acute LBP with the Numeric Rating Scale 0-10 (NRS). Linear mixed models (LMM) were used to analyze the association of the independent variables with pain intensity over time. RESULTS: The mean baseline WUR was 1.3 (SD 0.6) for the right and 1.5 (SD 1.0) for the left side. STAI-S revealed a mean score of 43.1 (SD 5.2). Pain intensity was, on average, 5.4 points (SD 1.6) on the NRS and decreased over one year to a mean of 2.2 (SD 2.4). After one year, 56% of the participants still experienced pain. The LMM revealed a considerable variation, as seen in large confidence intervals. Therefore, associations of the independent variables (WUR and STAI-S) with the course of the outcome pain intensity over one year were not established. CONCLUSION: This investigation did not reveal an association of mechanical TS and state anxiety at baseline with pain intensity during the one-year measurement period. Pain persistence, mediated by central sensitization, is a complex mechanism that single mechanical TS and state anxiety cannot capture.

Temporal Summation of the Thermal Grill Illusion is Comparable to That Observed Following Noxious Heat.

The thermal grill illusion (TGI) describes a peculiar or even painful percept caused by non-noxious, interlaced warm and cold stimuli. It involves the glutamatergic system and is affected in putatively nociplastic syndromes such as fibromyalgia. The glutamatergic system is also involved in wind-up, that is, the increased activation of spinal neurons following repeated noxious stimulation leading to a temporal summation of perceived stimulus intensity. Here we combined both stimulation methods to further investigate whether non-noxious stimuli as employed in the TGI can lead to a similar summation of perceived stimulus intensity. In an experiment using a full crossover within-subjects design, 35 healthy volunteers received repeated stimuli, either in a thermal grill configuration or simply noxious heat. Both modalities were presented as sequences of 1 lead-in contact, followed by 11 consecutive contacts (each between 1.5 and 3 seconds), with either fast repetition ("wind-up" condition), or 2 slow-repeating control conditions. The main analyses concerned the relative pre-to-post sequence changes to quantify putatively wind-up-related effects. Pain ratings and skin conductance level (SCL) increased more strongly in "wind-up" than in control conditions. Interestingly, wind-up-related effects were of the same magnitude in TGI as compared to the pain control modality. Further, contact-by-contact SCL tracked how the effect emerged over time. These results indicate that although TGI does not involve noxious stimuli it is amenable to temporal summation and wind-up-like processes. Since both phenomena involve the glutamatergic system, the combination of wind-up with the TGI could yield a promising tool for the investigation of chronic pain conditions. PERSPECTIVE: Using thermal stimuli in an experimental protocol to combine 1) the TGI (painful or peculiar percept from simultaneous cold/warm stimulation) and 2) wind-up (increase in stimulus intensity after repeated exposure) holds promise to investigate pain and thermoceptive mechanisms, and chronic pain conditions.

Transspinal Focused Ultrasound Suppresses Spinal Reflexes in Healthy Rats.

OBJECTIVES: Low-intensity, focused ultrasound (FUS) is an emerging noninvasive neuromodulation approach, with improved spatial and temporal resolution and penetration depth compared to other noninvasive electrical stimulation strategies. FUS has been used to modulate circuits in the brain and the peripheral nervous system, however, its potential to modulate spinal circuits is unclear. In this study, we assessed the effect of trans-spinal FUS (tsFUS) on spinal reflexes in healthy rats. MATERIALS AND METHODS: tsFUS targeting different spinal segments was delivered for 1 minute, under anesthesia. Monosynaptic H-reflex of the sciatic nerve, polysynaptic flexor reflex of the sural nerve, and withdrawal reflex tested with a hot plate were measured before, during, and after tsFUS. RESULTS: tsFUS reversibly suppresses the H-reflex in a spinal segment-, acoustic pressure- and pulse-repetition frequency (PRF)-dependent manner. tsFUS with high PRF augments the degree of homosynaptic depression of the H-reflex observed with paired stimuli. It suppresses the windup of components of the flexor reflex associated with slower, C-afferent, but not faster, A- afferent fibers. Finally, it increases the latency of the withdrawal reflex. tsFUS does not elicit neuronal loss in the spinal cord. CONCLUSIONS: Our study provides evidence that tsFUS reversibly suppresses spinal reflexes and suggests that tsFUS could be a safe and effective strategy for spinal cord neuromodulation in disorders associated with hyperreflexia, including spasticity after spinal cord injury and painful syndromes.

Deep optimization design of 2D repetitive control systems with saturating actuators: An adaptive multi-population PSO algorithm.

This paper presents an optimization design method for a two-dimensional (2D) modified repetitive control system (MRCS) with an anti-windup compensator. Using lifting technology, a 2D hybrid model of the MRCS considering actuator saturation is established to describe the control and learning of the repetitive control. A linear-matrix-inequality (LMI)-based sufficient condition is derived to ensure the stability of the MRCS. Two tuning parameters, the selection of which is critical to the system design, are used in the LMI to adjust the control and learning, and hence the reference-tracking performance. A new cost function, developed through time domain analysis, directly evaluates the control performance of the system without calculating control errors, thus reducing the optimization time. Based on this cost function, an adaptive multi-population particle swarm optimization algorithm is presented to select an optimal pair of tuning parameters in which multiple populations cooperatively search in non-intersecting search intervals. An anti-windup term is added between the low-pass filter and the time delay in the modified repetitive controller to mitigate the undesirable effect of actuator saturation on system performance and stability. Simulations and experiments on the speed control of a rotation control system demonstrate the validity of the approach.

A sensorless anti-windup speed control approach to axial gap bearingless motors with nonlinear lumped mismatched disturbance observers.

In this paper, sensorless robust speed control with nonlinear lumped mismatched disturbance observers for a permanent magnet type axial gap bearingless motor (AGBM) is designed. Multistage anti-windup-based dynamic surface control combined with integral backstepping control is proposed to control the motor's axial displacement and rotor speed. The approach is against parameter uncertainties and external disturbances, improving steady-state accuracy, eliminating the derivative explosion phenomenon, no chattering problem, and reducing the magnitude of the control system when current saturation occurs. In addition, a novel nonlinear lumped mismatched disturbance observer is proposed to improve the approach under unmodeled dynamics and external disturbances. To obtain high-accuracy tracking control, the control system includes the robust controller combined with the disturbance observers and anticipatory activation of anti-windup (AW) compensation, which means the controller is more complex. Then, to design a sensorless robust speed control for the motor, the rotor position and speed observer require higher accuracy. High-gain back-EMF observer combined with an improved phase-locked loop is proposed to estimate rotor angular position and speed even when the motor speed is reversed. Overall stability of closed-loop system control, including a sensorless speed control approach for motors using back-EMF estimation combined with saturation of the currents and lumped disturbance observers, is mathematically proven. Finally, the simulation results under measurement noise show that the proposed control system are obtained the effectiveness, feasibility, and robustness.

Pain Science in Practice (Part 5): Central Sensitization II.

SYNOPSIS: Central sensitization is an umbrella-term for facilitated synaptic plasticity. This editorial explains wind-up, classical central sensitization, and long-term potentiation. Wind-up and LTP are generally considered homosynaptic, while classical central sensitization is classified as heterosynaptic. Wind-up is very short lived and unlikely to play a significant role in chronic musculoskeletal pain, however, both LTP and classical central sensitization could potentially be involved in chronic pain. J Orthop Sports Phys Ther 2023;53(2):55-58. doi:10.2519/jospt.2023.11571.

Anti-windup ADRC design for temperature control systems with output delay against asymmetric input constraint.

To tackle the asymmetric input constraint typically involved with industrial temperature control systems, e.g., there is a tuning range from 0 to 100% in the heating power, an anti-windup active disturbance rejection control (ADRC) is proposed for the practical application, in particular for dealing with output delay. Based on an artificial symmetric transformation for the asymmetric input constraint along with a delay-free output prediction, an anti-windup extended state observer (AESO) is firstly constructed to simultaneously estimate the delay-free system state and external disturbance for control design. When the input saturation constraint occurs, the proposed AESO could also offer anti-windup compensation. Then, a feedback controller is analytically derived by assigning repetitive-type poles for the characteristic equation of the closed-loop structure, followed by a set-point prefilter design to ensure no overshoot and output tracking deviation. Tractable linear matrix inequality based conditions are rigorously established to guarantee the asymptotic stability of the resulting closed-loop system under a specified initial condition. A benchmark example from a recent reference is used to verify the superiority of the proposed control method over some existing anti-windup control designs. Moreover, a real application to the temperature control of a jacketed crystallizer is shown in comparison with a recently developed control method with no anti-windup compensation.

Temporal Summation and Aftersensations of Second Pain in Women with Myofascial Temporomandibular Disorder Differ by Presence of Temporomandibular Joint Pain.

Purpose: Mechanisms underlying myofascial temporomandibular disorder (mTMD) are poorly understood. One theory is dysfunction in the central mediation of pain, specifically in enhanced facilitatory pain modulation. Because mechanisms leading to central sensitization may differ for joint and muscle pain, this study of mTMD addressed phenotypic heterogeneity by temporomandibular (TM) joint pain in the examination of quantitative sensory testing (QST). Patients and Methods: The stimulus dependent increase in second pain (temporal summation (TS)) and associated aftersensations (AS) were examined across groups of women with mTMD with TM joint pain and without, and a demographically matched control group. Results: TS was slightly more evident in mTMD without joint pain vs with (p = 0.035), but AS were most robustly persistent in the group with joint pain vs without (p < 0.002). Conclusion: While both subgroups demonstrated evidence of central sensitization relative to controls on one of two measures, differences in QST results, if replicated, may point to possible differences in the mechanisms that yield central sensitization. Alternatively, it may represent methodological artifacts that need to be addressed. Therefore, greater consideration should be given to symptom-based phenotypes in studies examining TS and AS.

The Effect of Palmitoylethanolamide on Pain Intensity, Central and Peripheral Sensitization, and Pain Modulation in Healthy Volunteers-A Randomized, Double-Blinded, Placebo-Controlled Crossover Trial.

Palmitoylethanolamide (PEA) is marketed as a "dietary food for special medical purposes". Its broad-spectrum analgesic, anti-inflammatory, and neuroprotective effects make PEA an interesting substance in pain management. However, the underlying analgetic mechanisms have not yet been investigated in humans. The aim of our study is to provide a deeper understanding of the involved mechanisms, which is essential for differentiating therapeutic approaches and the establishment of mechanism-based therapeutic approaches. In this randomized, placebo-controlled, double-blinded crossover trial, 14 healthy volunteers were included. PEA (3 × 400 mg per day) or placebo were taken for 4 weeks. Our study investigated the mode of action of PEA using an established pain model, "Repetitive phasic heat application", which is well-suited to investigate analgesic and anti-hyperalgesic effects in healthy volunteers. Parameters for peripheral and central sensitization as well as for pain modulation were assessed. Repetitive heat pain was significantly decreased, and the cold pain tolerance was significantly prolonged after the PEA treatment. The pressure pain tolerance and the conditioned pain modulation were increased after the PEA treatment. The wind-up ratio and the average distance of allodynia were significantly decreased after the PEA treatment. The heat pain tolerance was significantly higher after the PEA treatment. The present study has demonstrated that PEA has clinically relevant analgesic properties, acting on both peripheral and central mechanisms as well as in pain modulation.

NMDA and P2X7 Receptors Require Pannexin 1 Activation to Initiate and Maintain Nociceptive Signaling in the Spinal Cord of Neuropathic Rats.

Pannexin 1 (Panx1) is involved in the spinal central sensitization process in rats with neuropathic pain, but its interaction with well-known, pain-related, ligand-dependent receptors, such as NMDA receptors (NMDAR) and P2X7 purinoceptors (P2X7R), remains largely unexplored. Here, we studied whether NMDAR- and P2X7R-dependent nociceptive signaling in neuropathic rats require the activation of Panx1 channels to generate spinal central sensitization, as assessed by behavioral (mechanical hyperalgesia) and electrophysiological (C-reflex wind-up potentiation) indexes. Administration of either a selective NMDAR agonist i.t. (NMDA, 2 mM) or a P2X7R agonist (BzATP, 150 µM) significantly increased both the mechanical hyperalgesia and the C-reflex wind-up potentiation, effects that were rapidly reversed (minutes) by i.t. administration of a selective pannexin 1 antagonist (10panx peptide, 300 µM), with the scores even reaching values of rats without neuropathy. Accordingly, 300 µM 10panx completely prevented the effects of NMDA and BzATP administered 1 h later, on mechanical hyperalgesia and C-reflex wind-up potentiation. Confocal immunofluorescence imaging revealed coexpression of Panx1 with NeuN protein in intrinsic dorsal horn neurons of neuropathic rats. The results indicate that both NMDAR- and P2X7R-mediated increases in mechanical hyperalgesia and C-reflex wind-up potentiation require neuronal Panx1 channel activation to initiate and maintain nociceptive signaling in neuropathic rats.

Sodium-calcium exchanger-3 regulates pain "wind-up": From human psychophysics to spinal mechanisms.

Repeated application of noxious stimuli leads to a progressively increased pain perception; this temporal summation is enhanced in and predictive of clinical pain disorders. Its electrophysiological correlate is "wind-up," in which dorsal horn spinal neurons increase their response to repeated nociceptor stimulation. To understand the genetic basis of temporal summation, we undertook a GWAS of wind-up in healthy human volunteers and found significant association with SLC8A3 encoding sodium-calcium exchanger type 3 (NCX3). NCX3 was expressed in mouse dorsal horn neurons, and mice lacking NCX3 showed normal, acute pain but hypersensitivity to the second phase of the formalin test and chronic constriction injury. Dorsal horn neurons lacking NCX3 showed increased intracellular calcium following repetitive stimulation, slowed calcium clearance, and increased wind-up. Moreover, virally mediated enhanced spinal expression of NCX3 reduced central sensitization. Our study highlights Ca2+ efflux as a pathway underlying temporal summation and persistent pain, which may be amenable to therapeutic targeting.

A Minimally Invasive Method for Observing Wind-Up of Flexion Reflex in Humans: Comparison of Electrical and Magnetic Stimulation.

Wind-up like pain or temporal summation of pain is a phenomenon in which pain sensation is increased in a frequency-dependent manner by applying repeated noxious stimuli of uniform intensity. Temporal summation in humans has been studied by observing the increase in pain or flexion reflex by repetitive electrical or thermal stimulations. Nonetheless, because the measurement is accompanied by severe pain, a minimally invasive method is desirable. Gradual augmentation of flexion reflex and pain induced by repetitive stimulation of the sural nerve was observed using three stimulation methods-namely, bipolar electrical, magnetic, and monopolar electrical stimulation, with 11 healthy male subjects in each group. The effects of frequency, intensity, and number of repetitive stimuli on the increase in the magnitude of flexion reflex and pain rating were compared among the three methods. The reflex was measured using electromyography (EMG) from the short head of the biceps femoris. All three methods produced a frequency- and intensity-dependent progressive increase in reflex and pain; pain scores were significantly lower for magnetic and monopolar stimulations than for bipolar stimulation (P < 0.05). The slope of increase in the reflex was steep during the first 4-6 stimuli but became gentler thereafter. In the initial phase, an increase in the reflex during the time before signals of C-fibers arrived at the spinal cord was observed in experiments using high-frequency stimulation, suggesting that wind-up was caused by inputs of A-fibers without the involvement of C-fibers. Magnetic and monopolar stimulations are minimally invasive and useful methods for observing the wind-up of the flexion reflex in humans. Monopolar stimulation is convenient because it does not require special equipment. There is at least a partial mechanism underlying the wind-up of the flexion reflex that does not require C-fibers.

Making the PI and PID Controller Tuning Inspired by Ziegler and Nichols Precise and Reliable.

This paper deals with the design of a DC motor speed control implemented by an embedded controller. The design is simple and brings some important changes to the traditional Ziegler-Nichols tuning. The design also includes a novel anti-windup implementation of the controller and an integrated noise-reduction filter design. The proposed tuning method considers all important aspects of the control, such as pre-processing of the measured signals and filtering (to attenuate the measurement noise), time delays of the process, modeling and identification of the process, and constraints on the control signal. Three important aspects of designing PI and PID controllers for processes with noisy output on Arduino-type embedded computers are considered. First, it deals with the integrated design of the input filter and the controller parameters, since both are interdependent. Secondly, the method of setting the controllers from step responses by Ziegler and Nichols is modified for the case of digital signal processing (without drawing the tangent), while it recommends the suitability of its modification in terms of the use of both integral and static models. Third, the most suitable anti-windup solution for the given controller structure is proposed. In summary, the paper shows that an appropriate design of the embedded controller can achieve excellent closed-loop performance even in a noisy process environment with limited control signals.

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

The cause for the increased sensitivity of patients with fibromyalgia (FM) to painful stimuli is unclear but sensitization of dorsal horn spinal cord neurons has been suggested. There, critical changes of sensory information occur which depend on the plasticity of second-order neurons and descending pain modulation, including facilitation and inhibition. This study used repetitive stimuli that produce temporal-summation-of-second-pain (TSSP) and central sensitization, relevant mechanisms for patients with chronic pain. We examined spinal cord neural activation during TSSP in patients with FM and healthy controls (HC) and used its functional connectivity with several brainstem nuclei to model the observed blood-oxygen-level-dependent (BOLD) time-course with pain ratings. Sixteen HC and 14 FM participants received repetitive heat stimuli to the hand at 0.4 Hz to achieve TSSP during functional imaging with a 3 T-Philips Achieva MRI scanner. Stimuli were adjusted to each individual's pain sensitivity to achieve maximal pain ratings of 50 ± 10 on a numerical pain scale (0-100). Using a 16-channel neurovascular coil, multiple image series were obtained from the cervical spinal cord to the brainstem using single-shot turbo-spin echo sequences. During repetitive, sensitivity-adjusted heat stimuli, pain ratings of all subjects increased as predicted, consistent with TSSP. HC and FM participants had similar temporal patterns of spinal activation: initial BOLD increase followed by deactivation. Structural equation modeling showed that the observed spinal activity during TSSP was associated with more BOLD activity across/within the brainstem in FM subjects than HC, suggesting differences in pain modulation.NEW & NOTEWORTHY "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.