Intense and sustained pain reduces cortical responses to auditory stimuli: Implications for the interpretation of the effects of heterotopic noxious conditioning stimulation in humans.

Phasic pain stimuli are inhibited when they are applied concomitantly with a conditioning tonic stimulus at another body location (heterotopic noxious conditioning stimulation, HNCS). While the effects of HNCS are thought to rely on a spino-bulbo-spinal mechanism in animals (termed diffuse noxious inhibitory controls, DNIC), the underlying neurophysiology in humans may involve other pathways. In this study, we investigated the role of concomitant supraspinal mechanisms during HNCS by presenting auditory stimuli during a conditioning tonic painful stimulus (the cold pressor test, CPT). Considering that auditory stimuli are not conveyed through the spinal cord, any changes in brain responses to auditory stimuli during HNCS can be ascribed entirely to supraspinal mechanisms. Electroencephalography (EEG) was recorded during HNCS, and auditory stimuli were administered in three blocks, before, during and after HNCS. Nociceptive withdrawal reflexes (NWRs) were recorded at the same time points to investigate spinal processing. Our results showed that AEPs were significantly reduced during HNCS. Moreover, the amplitude of the NWR was significantly diminished during HNCS in most participants. Given that spinal and supraspinal mechanisms operate concomitantly during HNCS, the possibility of isolating their individual contributions in humans is questionable. We conclude that the net effects of HCNS are not independent from attentional/cognitive influences.

Can quantitative sensory tests predict failed back surgery?: A prospective cohort study.

BACKGROUND: Failed back surgery syndrome (FBSS) is a pain condition refractory to therapy, and is characterised by persistent low back pain after spinal surgery. FBSS is associated with severe disability, low quality of life and high unemployment. We are currently unable to identify patients who are at risk of developing FBSS. Patients with chronic low back pain may display signs of central hypersensitivity as assessed by quantitative sensory tests (QST). This can contribute to the risk of developing persistent pain after surgery. OBJECTIVE: We tested the hypothesis that central hypersensitivity as assessed by QST predicts FBSS. DESIGN: Prospective cohort study. SETTING: Three tertiary care centres. PATIENTS: 141 patients scheduled for up to three segment spinal surgery for chronic low back pain (defined as at least 3 on a numerical rating scale on most days during the week and with a minimum duration of 3 months) due to degenerative changes. OUTCOMES: We defined FBSS as persistent pain, persistent disability or a composite outcome defined as either persistent pain or disability. The primary outcome was persistent pain 12 months after surgery. We applied 14 QST using electrical, pressure and temperature stimulation to predict FBSS and assessed the association of QST with FBSS in multivariable analyses adjusted for sociodemographic, psychological and clinical and surgery-related characteristics. RESULTS: None of the investigated 14 QST predicted FBSS, with 95% confidence intervals of crude and adjusted associations of all QST including one as a measure of no association. Results remained robust in all sensitivity and secondary analyses. CONCLUSION: The study indicates that assessment of altered central pain processing using current QST is unlikely to identify patients at risk of FBSS and is therefore unlikely to inform clinical decisions.

Membrane properties in small cutaneous nerve fibers in humans.

INTRODUCTION: Assessment of membrane properties is important for understanding the mechanisms of painful peripheral neuropathy, developing new diagnostic techniques, and screening/profiling of analgesics that target ion channels. METHODS: Small cutaneous nerves were activated electrically by small diameter (0.2 mm) cathodes, and large nerves were activated by ordinary patch electrodes. This new perception threshold tracking method combines perception threshold assessment and stimulation paradigms from conventional threshold tracking. RESULTS: The strength-duration time-constant of large fibers (580 µs ± 160 µs) was lower than the time constant of small fibers (1060 µs ± 690 µs; P < 0.01, paired t-test). Threshold electrotonus showed similar threshold reductions to sub-threshold prepulses, except for 80 ms hyperpolarizing prepulses, to which small fibers showed less threshold reduction than large fibers (repeated-measures analysis of variance, Bonferroni, P = 0.006). CONCLUSIONS: This is a reliable method to investigate the membrane properties of small cutaneous nerve fibers in humans and may be used in clinical settings as a diagnostic or profiling tool. Muscle Nerve 55: 195-201, 2017.

Design and test of an automated version of the modified Jebsen test of hand function using Microsoft Kinect.

BACKGROUND: The present paper describes the design and evaluation of an automated version of the Modified Jebsen Test of Hand Function (MJT) based on the Microsoft Kinect sensor. METHODS: The MJT was administered twice to 11 chronic stroke subjects with varying degrees of hand function deficits. The test times of the MJT were evaluated manually by a therapist using a stopwatch, and automatically using the Microsoft Kinect sensor. The ground truth times were assessed based on inspection of the video-recordings. The agreement between the methods was evaluated along with the test-retest performance. RESULTS: The results from Bland-Altman analysis showed better agreement between the ground truth times and the automatic MJT time evaluations compared to the agreement between the ground truth times and the times estimated by the therapist. The results from the test-retest performance showed that the subjects significantly improved their performance in several subtests of the MJT, indicating a practice effect. CONCLUSIONS: The results from the test showed that the Kinect can be used for automating the MJT.

Ipsilateral resistance exercise prevents exercise-induced central sensitization in the contralateral limb: a randomized controlled trial.

PURPOSE: This study aimed to investigate the hypothesis that a repeated bout of eccentric exercise (ECC2) would result in smaller increase in the sensitivity of spinal nociceptive system, and smaller decrease in the local muscle blood oxygenation response in both the ipsilateral and the contralateral tibialis anterior muscle (TA) when compared with the initial bout (ECC1). It was hypothesized that the magnitude of the repeated bout effect (RBE) would be greater for the ipsilateral side than the contralateral side. METHODS: Twenty-six healthy young men performed two bouts of high-intensity eccentric exercise of TA separated by 2 weeks. Half of the participants used the same leg for both bouts (IPSI) and the other half used the contralateral leg for ECC2 (CONTRA). Nociceptive withdrawal reflex threshold (NWRT) and local muscle blood oxygenation were assessed for the exercised TA muscle before, immediately after, and one day after exercise. RESULTS: Significant decreases in NWRT and muscle oxygenation were observed after ECC1 (p < 0.05), but NWRT did not change after ECC2 in both groups. Smaller decreases in muscle oxygenation were observed after ECC2 than ECC1 in both groups with a similar magnitude of the difference between bouts, but an increase in muscle oxygen re-perfusion before ECC2 was only observed in the IPSI group. CONCLUSION: These results suggest that contralateral RBE was associated with spinal facilitation of the neuronal pathways situated at a homologous innervation level, and it is unlikely that oxygen re-perfusion improvement plays a major role in the contralateral RBE.

Adaptation of local muscle blood flow and surface electromyography to repeated bouts of eccentric exercise.

The aim of this randomized controlled crossover study was to investigate the effect of a bout of unaccustomed eccentric exercise (ECC) followed by a consecutive bout of the same intensity on local muscle blood flow, amplitude, and frequency of the electromyographic (EMG) signal from the exercised tibialis anterior muscle. Sixteen healthy male participants (age, 25.7 (0.6) years; body mass index 24.8 (1) kg·m(-2) participated in this study. Two identical bouts of high-intensity ECC were performed on the tibialis anterior muscle 7 days apart. Control sessions involving no exercise were performed 4 weeks either before or after the exercise sessions. Changes in local total blood flow [ΔtHb], EMG root mean square, and median power frequency were recorded during isometric maximum voluntary contraction of ankle dorsiflexion. Measurements were performed before, immediately after, and the day after both ECCs (ECC1 and ECC2). The participants rested quietly in a chair in the control session. Eccentric exercise 1 led to a significant decrease in [ΔtHb] on the day after (p ≤ 0.05), whereas ECC2 did not. Median power frequency decreased significantly in ECC2 compared with ECC1 (p < 0.01). Root mean square was unchanged in all the instants. The present study showed that adaptation is depicted in the local muscle blood flow and the frequency contents of the EMG after an unaccustomed ECC inducing muscle soreness. These alterations provide a potential mechanism for a rapid adaptation, which decreases susceptibility of the muscle to develop further soreness in the subsequent ECC bout.

Probabilistic model for individual assessment of central hyperexcitability using the nociceptive withdrawal reflex: a biomarker for chronic low back and neck pain.

BACKGROUND: The nociceptive withdrawal reflex (NWR) has been proven to be a valuable tool in the objective assessment of central hyperexcitability in the nociceptive system at spinal level that is present in some chronic pain disorders, particularly chronic low back and neck pain. However, most of the studies on objective assessment of central hyperexcitability focus on population differences between patients and healthy individuals and do not provide tools for individual assessment. In this study, a prediction model was developed to objectively assess central hyperexcitability in individuals. The method is based on statistical properties of the EMG signals associated with the nociceptive withdrawal reflex. The model also supports individualized assessment of patients, including an estimation of the confidence of the predicted result. RESULTS: up to 80% classification rates were achieved when differentiating between healthy volunteers and chronic low back and neck pain patients. EMG signals recorded after stimulation of the anterolateral and heel regions and of the sole of the foot presented the best prediction rates. CONCLUSIONS: A prediction model was proposed and successfully tested as a new approach for objective assessment of central hyperexcitability in the nociceptive system, based on statistical properties of EMG signals recorded after eliciting the NWR. Therefore, the present statistical prediction model constitutes a first step towards potential applications in clinical practice.

Pain sensitivity is normalized after a repeated bout of eccentric exercise.

PURPOSE: The purpose of this study was to investigate the effect of repeated bouts of eccentric exercise on the nociceptive withdrawal reflex (NWR) threshold, a measure of sensitivity in the spinal nociceptive system. METHODS: Sixteen healthy students (age 25.7 ± 0.6 years, BMI 24.8 ± 1 kg m(-2)) participated in this randomized, controlled, crossover study. Two identical bouts of high-intensity eccentric exercises were performed on the tibialis anterior muscle 7 days apart. Control sessions involving no exercise were performed 4 weeks apart the exercise sessions. Pressure pain thresholds (PPT) and the NWR threshold were recorded before, immediately after, and 1 day after both bouts of exercise. RESULTS: Pressure pain thresholds decreased significantly at two of the muscle belly sites on the day after initial bout compared with baseline. NWR threshold decreased by 25 ± 4 % immediately after initial bout and by 30 ± 5 % the next day (p < 0.05) as an indication of generalized pain hypersensitivity. On the contrary, no changes were found in both pain thresholds after second bout of eccentric exercise indicating that both localized and generalized pain sensitivity were normalized. CONCLUSION: In conclusion, this study for the first time documented that an initial bout of unaccustomed high-intensity eccentric exercise, which results in muscle soreness can induce central sensitization. A repeated bout of exercise, however, facilitates inherent protective spinal mechanisms against the development of muscle soreness.

Orbital reflectometry of oxide heterostructures.

The occupation of d orbitals controls the magnitude and anisotropy of the inter-atomic electron transfer in transition-metal oxides and hence exerts a key influence on their chemical bonding and physical properties. Atomic-scale modulations of the orbital occupation at surfaces and interfaces are believed to be responsible for massive variations of the magnetic and transport properties, but could not thus far be probed in a quantitative manner. Here we show that it is possible to derive quantitative, spatially resolved orbital polarization profiles from soft-X-ray reflectivity data, without resorting to model calculations. We demonstrate that the method is sensitive enough to resolve differences of ~3% in the occupation of Ni e(g) orbitals in adjacent atomic layers of a LaNiO(3)-LaAlO(3) superlattice, in good agreement with ab initio electronic-structure calculations. The possibility to quantitatively correlate theory and experiment on the atomic scale opens up many new perspectives for orbital physics in transition-metal oxides.

Gutzwiller theory of band magnetism in LaOFeAs.

We use the Gutzwiller variational theory to calculate the ground-state phase diagram and quasiparticle bands of LaOFeAs. The Fe3d-As4p Wannier-orbital basis obtained from density-functional theory defines the band part of our eight-band Hubbard model. The full atomic interaction between the electrons in the iron orbitals is parametrized by the Hubbard interaction U and an average Hund's-rule interaction J. We reproduce the experimentally observed small ordered magnetic moment over a large region of (U,J) parameter space. The magnetically ordered phase is a stripe spin-density wave of quasiparticles.

Surface EMG crosstalk during phasic involuntary muscle activation in the nociceptive withdrawal reflex.

The human nociceptive withdrawal reflex is typically assessed using surface electromyography (sEMG). Based on sEMG, the reflex receptive field (RRF) can be mapped. However, EMG crosstalk can cause erroneous results in the RRF determination. Single differential (SD) vs. double differential (DD) surface EMG were evaluated. Different electrode areas and inter-electrode-distances (IED) were evaluated. The reflexes were elicited by electrical stimulation of the sole of the foot. EMG was obtained from both tibialis anterior (TA) and soleus (SOL) using both surface and intramuscular EMG (iEMG). The amount of crosstalk was significantly higher in SD recordings than in DD recordings (P < 0.05). Crosstalk increased when electrode measuring area increased (P < 0.05) and when IED increased (P < 0.05). Reflex detection sensitivity decreases with increasing measuring area and increasing IED. These results stress that for determination of RRF and similar tasks, DD recordings should be applied.

Test-retest reliability of the nociceptive withdrawal reflex and electrical pain thresholds after single and repeated stimulation in patients with chronic low back pain.

Recent studies have shown that the nociceptive withdrawal reflex threshold (NWR-T) and the electrical pain threshold (EP-T) are reliable measures in pain-free populations. However, it is necessary to investigate the reliability of these measures in patients with chronic pain in order to translate these techniques from laboratory to clinic. The aims of this study were to determine the test-retest reliability of the NWR-T and EP-T after single and repeated (temporal summation) electrical stimulation in a group of patients with chronic low back pain, and to investigate the association between the NWR-T and the EP-T. To this end, 25 patients with chronic pain participated in three identical sessions, separated by 1 week in average, in which the NWR-T and the EP-T to single and repeated stimulation were measured. Test-retest reliability was assessed using intra-class correlation coefficient (ICC), coefficient of variation (CV), and Bland-Altman analysis. The association between the thresholds was assessed using the coefficient of determination (r (2)). The results showed good-to-excellent reliability for both NWR-T and EP-T in all cases, with average ICC values ranging 0.76-0.90 and average CV values ranging 12.0-17.7%. The association between thresholds was better after repeated stimulation than after single stimulation, with average r (2) values of 0.83 and 0.56, respectively. In conclusion, the NWR-T and the EP-T are reliable assessment tools for assessing the sensitivity of spinal nociceptive pathways in patients with chronic pain.

Cold pain hypersensitivity predicts trajectories of pain and disability after low back surgery: a prospective cohort study.

Improving the ability to predict persistent pain after spine surgery would allow identification of patients at risk and guide treatment decisions. Quantitative sensory tests (QST) are measures of altered pain processes, but in our previous study, preoperative QST did not predict pain and disability at single time-points. Trajectory analysis accounts for time-dependent patterns. We hypothesized that QST predict trajectories of pain and disability during 1 year after low back surgery. We performed a trajectory analysis on the cohort of our previous study (n = 141). Baseline QST included electrical, pressure, heat, and cold stimulation of the low back and lower extremity, temporal summation, and conditioned pain modulation. Pain intensity and Oswestry Disability Index were measured before, and 2, 6, and 12 months after surgery. Bivariate trajectories for pain and disability were computed using group-based trajectory models. Multivariable regressions were used to identify QST as predictors of trajectory groups, with sociodemographic, psychological, and clinical characteristics as covariates. Cold pain hypersensitivity at the leg, not being married, and long pain duration independently predicted worse recovery (complete-to-incomplete, incomplete-to-no recovery). Cold pain hypersensitivity increased the odds for worse recovery by 3.8 (95% confidence intervals 1.8-8.0, P < 0.001) and 3.0 (1.3-7.0, P = 0.012) in the univariable and multivariable analyses, respectively. Trajectory analysis, but not analysis at single time-points, identified cold pain hypersensitivity as strong predictor of worse recovery, supporting altered pain processes as predisposing factor for persisting pain and disability, and a broader use of trajectory analysis. Assessment of cold pain sensitivity may be a clinically applicable, prognostic test.

Neurophysiological correlates of nociceptive heterosynaptic long-term potentiation in humans.

Long-term potentiation (LTP) is a cellular model of synaptic plasticity and reflects an increase of synaptic strength. LTP is also present in the nociceptive system and is believed to be one of the key mechanisms involved in the manifestations of chronic pain. LTP manifested as an increased response in pain perception can be induced in humans using high-frequency electrical stimulation (HFS). The aim of this study was to induce spinal heterosynaptic LTP using HFS and investigate its heterotopic effects on event-related potentials (ERPs) to repeated nonpainful cutaneous stimuli as a possible electrophysiological cortical correlate of sensitization. Twenty-two healthy subjects were randomly assigned to one of the two experimental conditions: HFS and control stimulation. Before and after the stimulation, both conditions received heterotopic mechanical (pinprick) and paired nonpainful electrical test stimuli to quantify and confirm the effects of HFS on the behavioral level. ERPs to paired nonpainful electrical stimulation were measured simultaneously. Conditioning HFS resulted in significant heterotopic effects after 30 min, including increased perceived intensity in response to (pinprick) mechanical and paired nonpainful electrical stimulation compared with control. The paired nonpainful electrical stimuli were accompanied by significantly enhanced responses regarding the ERP N1-P2 peak-to-peak and P300 amplitude compared with control. These findings suggest that HFS is capable of producing heterosynaptic spinal LTP that can be measured not only behaviorally but also using ERPs.

Spatial temperature distribution in human hairy and glabrous skin after infrared CO2 laser radiation.

BACKGROUND: CO2 lasers have been used for several decades as an experimental non-touching pain stimulator. The laser energy is absorbed by the water content in the most superficial layers of the skin. The deeper located nociceptors are activated by passive conduction of heat from superficial to deeper skin layers. METHODS: In the current study, a 2D axial finite element model was developed and validated to describe the spatial temperature distribution in the skin after infrared CO2 laser stimulation. The geometry of the model was based on high resolution ultrasound scans. The simulations were compared to the subjective pain intensity ratings from 16 subjects and to the surface skin temperature distributions measured by an infrared camera. RESULTS: The stimulations were sensed significantly slower and less intense in glabrous skin than they were in hairy skin (MANOVA, p < 0.001). The model simulations of superficial temperature correlated with the measured skin surface temperature (r > 0.90, p < 0.001). Of the 16 subjects tested; eight subjects reported pricking pain in the hairy skin following a stimulus of 0.6 J/cm2 (5 W, 0.12 s, d1/e2 = 11.4 mm) only two reported pain to glabrous skin stimulation using the same stimulus intensity. The temperature at the epidermal-dermal junction (depth 50 µm in hairy and depth 133 µm in glabrous skin) was estimated to 46°C for hairy skin stimulation and 39°C for glabrous skin stimulation. CONCLUSIONS: As compared to previous one dimensional heat distribution models, the current two dimensional model provides new possibilities for detailed studies regarding CO2 laser stimulation intensity, temperature levels and nociceptor activation.

New method for quantification and statistical analysis of nociceptive reflex receptive fields in humans.

A method for quantifying nociceptive withdrawal reflex receptive fields in human volunteers and patients is described. The reflex receptive field (RRF) for a specific muscle denotes the cutaneous area from which a muscle contraction can be evoked by a nociceptive stimulus. The method is based on random stimulations presented in a blinded sequence to 10 stimulation sites. The sensitivity map is derived by interpolating the reflex responses evoked from the 10 sites. A set of features describing the size and location of the RRF is presented based on statistical analysis of the sensitivity map within every subject. The features include RRF area, volume, peak location and center of gravity. The method was applied to 30 healthy volunteers. Electrical stimuli were applied to the sole of the foot evoking reflexes in the ankle flexor tibialis anterior. The RRF area covered a fraction of 0.57+/-0.06 (S.E.M.) of the foot and was located on the medial, distal part of the sole of the foot. An intramuscular injection into flexor digitorum brevis of capsaicin was performed in one spinal cord injured subject to attempt modulation of the reflex receptive field. The RRF area, RRF volume and location of the peak reflex response appear to be the most sensitive measures for detecting modulation of spinal nociceptive processing. This new method has important potential applications for exploring aspects of central plasticity in volunteers and patients. It may be utilized as a new diagnostic tool for central hypersensitivity and quantification of therapeutic interventions.

Independent psychophysical measurement of experimental modulations in the somatotopy of cutaneous heat-pain stimuli.

Distortions of the body image have been repeatedly reported for various clinical conditions, but direct experimental analyses of the perceptual changes involved are still scarce. In addition, most experimental studies rely on cerebral activation patterns to assess neuroplastic changes in central representation, although the relationship between cerebral topography and the topology of the perceptual space is not clear. This study examines whether the direct psychophysical mapping approach we introduced recently (Trojan et al., Brain Res 2006;1120:106-113) is capable of tracking perceptual distortions in the somatotopic representation of heat-pain stimuli. Eleven healthy participants indicated the perceived positions of CO(2) laser stimuli, repetitively presented to the dorsal forearm, with a 3D tracking system in two consecutive sessions, separated by the topical application of capsaicin cream. In line with earlier reports, we expected that the resulting individual perceptual maps (i.e., one-dimensional projections of the perceived positions onto the forearm surface) would be subject to modulation through the altered sensory input, to be measured in terms of altered topological parameters. We found that the topology and metrics of the somatotopic representation were well preserved in the second session, but that the perceptual map was compressed to a smaller range in 9 out of 11 participants. By providing dimensional measures of perceptual representations, perceptual maps constitute an independent, genuinely psychological complement to the topography of cortical activations measured with neuroimaging methods. In addition, we expect them to be useful in diagnosing pathological changes in body perception accompanying chronic pain and other disorders.

Modulation of nociceptive withdrawal reflexes evoked by single and repeated nociceptive stimuli in conscious dogs by low-dose acepromazine.

OBJECTIVES: To investigate the modulation of the nociceptive withdrawal reflex (NWR) and temporal summation (TS) by low-dose acepromazine (ACP) in conscious dogs. To assess the short- and long-term stability of the reflex thresholds. STUDY DESIGN: Randomized, blinded, placebo-controlled cross-over experimental study. ANIMALS: Eight adult male Beagles. METHODS: The NWR was elicited using single transcutaneous electrical stimulation of the ulnar nerve. Repeated stimuli (10 pulses, 5 Hz) were applied to evoke TS. The responses of the deltoideus muscle were recorded and quantified by surface electromyography and the behavioural reactions were scored. Each dog received 0.01 mg kg(-1) ACP or an equal volume saline intravenously (IV) at 1 week intervals. Measurements were performed before (baseline) and 20, 60 and 100 minutes after drug administration. Sedation was scored before drug administration and then at 10 minutes intervals. Data were analyzed with Friedman repeated measures analysis of variance on ranks and Wilcoxon signed rank tests. RESULTS: Acepromazine resulted in a mild tranquilization becoming obvious at 20 minutes and peaking 30 minutes after injection. Single (I(t)) and repeated stimuli (TS(t)) threshold intensities, NWR and TS characteristics and behavioural responses were not affected by the ACP at any time point. Both I(t) and TS(t) were stable over time. CONCLUSIONS AND CLINICAL RELEVANCE: In dogs, 0.01 mg kg(-1) ACP IV had no modulatory action on the NWR evoked by single or repeated stimuli, suggesting no antinociceptive activity on phasic nociceptive stimuli. The evidence of the stability of the NWR thresholds supports the use of the model as an objective tool to investigate nociception in conscious dogs. A low dose of ACP administered as the sole drug, can be used to facilitate the recordings in anxious subjects without altering the validity of this model.

A new experimental model of muscle pain in humans based on short-wave diathermy.

BACKGROUND: Experimental models of pain in humans are crucial for understanding pain mechanisms. The most often used muscle pain models involve the injection of algesic substances, such as hypertonic saline solution or nerve growth factor or the induction of delayed onset muscle soreness (DOMS) by an unaccustomed exercise routine. However, these models are either invasive or take substantial time to develop, and the elicited level of pain/soreness is difficult to control. To overcome these shortcomings, we propose to elicit muscle pain by a localized application of short-wave diathermy (SWD). METHODS: In this crossover study, SWD was administered to 18 healthy volunteers to the wrist extensor muscle group, with a constant stimulation intensity and up to 4 min. Pressure pain threshold (PPT), pinprick sensitivity (PPS) and self-reported muscle soreness were assessed at baseline and at 0, 30 and 60 min after application of SWD. RESULTS: SWD evoked localized muscle pain/soreness in the wrist extensor muscle group and a decrease of PPT in the treated arm compared with the control arm that lasted for at least 60 min, reflecting ongoing hyperalgesia after SWD application. PPS was not significantly altered 30-60 min following SWD, suggesting a minimal contribution from skin tissue to sustained hyperalgesia. CONCLUSIONS: SWD was able to elicit muscle soreness and hyperalgesia up to 60 min after its application. Thus, this new model represents a promising tool for investigating muscle pain in humans. SIGNIFICANCE: This study presents an experimental model to elicit sustained muscle pain based on short-wave diathermy. The main advantages of the model are its noninvasiveness, the possibility to control stimulation parameters in a reliable way and the convenience of the time frame in which pain and hyperalgesia are developed.

Homotopic and heterotopic variation in skin blood flow and temperature following experimental muscle pain in humans.

The aim of the present study was to explore variation in skin blood flow and temperature following experimental muscle pain. In 14 male human subjects, 2 ml and 4.8 ml of hypertonic (5.8%) saline were injected into the left tibialis anterior (TA) muscle to induce muscle pain. The subjects rated the pain intensity on a 10 cm visual analogue scale (VAS). Using laser-Doppler flowmetry and thermography, the skin blood flow and temperature were assessed at four different skin areas: ipsilateral muscle pain area (5x5 cm), ipsilateral referred pain area (5x10 cm), and two corresponding mirror areas on the contralateral non-injected leg. Compared with 2 ml hypertonic saline injection, significantly longer pain duration (1599+/-119 s) and stronger pain intensity (VAS peak: 6.9+/-0.6 cm) were found after the injection of 4.8 ml hypertonic saline (P<0.001, respectively). In addition, 4.8 ml hypertonic saline evoked a significant increase in skin blood flow and higher skin temperature around the injection site, the referred pain area, and the contralateral area to the injection site (P<0.05). By contrast, 2 ml hypertonic saline injection only elicited an increase in skin blood flow, but not temperature, at the injection area and the contralateral mirror area to the injection site (P<0.05). These results suggested that the vasodilation in different skin areas following intramuscular injection of hypertonic saline was dose-dependent. Injection of 4.8 ml hypertonic saline after local intramuscular anesthesia (2% lidocaine) did not evoke any significant changes in skin blood flow or skin temperature in any of the four observation areas. This suggested that both homotopic and heterotopic vascular reactions triggered by hypertonic saline stimulation of thin muscle afferent fibers were a neurogenically associated reaction.