Vibrotactile subjective magnitude as a function of hand preference

Reply to the letter to the editor by G. Michaux

IntroductionApplication of noxious stimulation to one body area reduces pain sensitivity in a remote body area through activation of an endogenous pain-inhibitory network, a behavioral phenomenon referred to as conditioned pain modulation (CPM). The efficiency of CPM is predictive of a variety of health outcomes, while impaired CPM has been associated with various chronic pain conditions. Current methods used to assess CPM vary widely, and interest in CPM method development remains strong. Here, we evaluated a novel method for assessing CPM in healthy controls and fibromyalgia (FM) patients using thumb pressure as both a test and conditioning stimulus.MethodsSixteen female FM patients and 14 matched healthy controls underwent CPM testing with thumbnail pressure as the test stimulus, and either cold water or noxious pressure as the conditioning stimulus. CPM magnitude was evaluated as the difference in pain rating of the test stimulus applied before and during the conditioning stimulus.ResultsIn healthy controls, application of either pressure or cold water conditioning stimulation induced CPM as evidenced by a significant reduction in test stimulus pain rating during conditioning (P=0.007 and P=0.021, respectively). In contrast, in FM patients, neither conditioning stimulus induced a significant CPM effect (P>0.274). There was a significant difference in CPM magnitude for FM patients compared to healthy controls with noxious pressure conditioning stimulation (P=0.023); however, no significant difference in CPM was found between groups using cold water as a conditioning stimulus (P=0.269).ConclusionThe current study demonstrates that thumbnail pressure can be used as both a test and conditioning stimulus in the assessment of CPM. This study further confirms previous findings of attenuated CPM in FM patients compared with healthy controls.

Reliability of conditioned pain modulation in healthy individuals and chronic pain patients: a systematic review and meta-analysis.

Electrical-induced pain diminishes somatosensory evoked magnetic cortical fields.

A heteronymous H reflex in the temporalis muscle can be elicited by selective stimulation of the masseteric nerve. The present study aimed at defining the optimal amplitude of the H reflex to detect inhibitory changes induced by stimulation of the perioral afferents and at providing new information on the control of masticatory muscles. Sixteen healthy volunteers participated in the experiment. A conditioning stimulus (CS) to the perioral skin was applied at various delays before an ipsilateral selective masseteric nerve stimulation (test stimulus: TS) while the subject was clenching the teeth at 25% of the maximal voluntary contraction. Two intensities of CS and TS were employed, high and low. The peak-to-peak amplitude of the H reflex (TS) and the root-mean-square value of the preceding electromyography were measured and the data analyzed by three-way analysis of variance and Tukey's posthoc tests. For both intensities used the heteronymous H reflex in the temporalis muscle was significantly decreased by prior activation of perioral afferents for delays from 5 to 60 ms. With a delay of 5 and 35 ms the preceding EMG level was not changed, while it was reduced at 20 and 60 ms delay. The intensities used to elicit the heteronymous H reflex of the temporalis muscle were appropriate to detect a reduction in motoneuron excitability. The reduction in the H reflex without a change in the preceding EMG at 5 and 35 ms delays could be due to presynaptic inhibition of the masseteric afferents exerted by the ipsilateral perioral afferents.

Background and ObjectivesZZWhile vestibular evoked myogenic potentials (VEMPs) can be measured from extra-ocular muscle as well as cervical muscle, there are uncertainties about the patterns and discomfort level of ocular vestibular evoked myogenic potentials (oVEMPs). This study is to identify the properties of oVEMPs parameters and degree of subjective discomfort when compared to cervical vestibular evoked myogenic potentials (cVEMPs) in healthy subjects. Subjects and MethodZZTwenty volunteers with normal hearing were enrolled in this study. The oVEMPs were recorded from electrodes placed beneath the eyes using ipsilateral and contralateral acoustic stimulation with 500 Hz short tone bursts with subjects in sitting position and maximal upward gaze. The cVEMPs were measured using 500 Hz short tone bursts with subject in supine position and their head elevated and turned away from the test side. The latency, interlatency and interamplitude of oVEMPs responses were compared to those of cVEMPs. The subjective discomfort levels of oVEMPs and cVEMPs were compared using a questionnaire survey. ResultsZZThe cVEMPs appeared as positive-negative biphasic responses in all 40 ears whereas oVEMPs were measured in 27 ears (67.5%) with ipsilateral stimulation and 20 ears (85%) with contralateral stimulation which appeared as negative-positive biphasic responses. The oVEMPs had smaller amplitude than the cVEMPs. The oVEMPs thresholds tended to have higher level than the cVEMPs thresholds. The 18 subjects (90%) reported that the discomfort level of oVEMPs measurement was lower or equal to that of cVEMPs measurement. ConclusionZZoVEMPs test may be used as a complementary and comfortable diagnostic tool for evaluating the integrity of vestibular-ocular system. Korean J Otorhinolaryngol-Head Neck Surg 2009;52:968-73 Key WordsZZVestibulo-ocular reflex·Evoked potentials·Saccule·Otolith.

Peripheral and supraspinal loops activated by electrical stimulation of the tibial nerve were studied in alert monkeys. Weak conditioning stimuli below the threshold for muscle contraction and strong conditioning stimuli which elicited a direct motor response and an H-reflex were applied to the tibial nerve, while soleus EMG was recorded. The motoneuronal excitability was measured with a test H-reflex for different intervals between conditioning and test stimuli. A facilitation of the motoneuronal pool occurred with a latency of about 50 ms for weak, as well as strong, conditioning stimuli. The facilitation was superimposed on a long-lasting inhibition which was more pronounced when strong stimuli were used. The shape of the excitability curve of the motoneurons after strong conditioning stimuli was studied before and after various lesions. The shape of the curve did not change after an ipsilateral cerebellectomy except that the facilitation was more pronounced. A few days after pyramidotomy, the facilitation diminished in size but it recovered to its initial size after 3 months. Spinal hemisection did not abolish the facilitation. We concluded from these results that a peripheral loop was activated when conditioning stimuli above the threshold for a direct motor and reflex response were applied. The facilitation might be mediated by the muscle contraction and following activation of muscle afferents. Superimposed on thus loop is a previously demonstrated transcortical loop of similar latency.

To ensure animal welfare is not compromised, virtual fencing must be predictable and controllable, and this is achieved through associative learning. To assess the influence of predictability and controllability on physiological and behavioral responses to the aversive component of a virtual fence, two methods of training animals were compared. In the first method, positive punishment training involved sheep learning that after an audio stimulus, an electrical stimulus would follow only when they did not respond by stopping or turning at the virtual fence (predictable controllability). In the second method, classical conditioning was used to associate an audio stimulus with an electrical stimulus on all occasions (predictable uncontrollability). Eighty Merino ewes received one of the following treatments: control (no training and no stimuli in testing); positive punishment training with an audio stimulus in testing (PP); classical conditioning training with only an audio stimulus in testing (CC1); and classical conditioning training with an audio stimulus followed by electrical stimulus in testing (CC2). The stimuli were applied manually with an electronic collar. Training occurred on 4 consecutive days with one session per sheep per day. Sheep were then assessed for stress responses to the cues by measuring plasma cortisol, body temperature and behaviors. Predictable controllability (PP) sheep showed no differences in behavioral and physiological responses compared with the control treatment (P < 0.05). Predictable uncontrollability of receiving the aversive stimulus (CC2) induced a higher cortisol and body temperature response compared to the control but was not different to CC1 and PP treatments. CC2 treatment sheep showed a higher number of turning behaviors (P < 0.001), and more time spent running (P < 0.001) than the control and PP treatment groups, indicating that predictability without controllability was stressful. The behavior results also indicate that predicting the event without receiving it (CC1) was less stressful than predicting the event then receiving it (CC2), suggesting that there is a cost to confirmation of uncontrollability. These results demonstrate that a situation of predictability and controllability such as experienced when an animal successfully learns to avoid the aversive component of a virtual fence, induces a comparatively minimal stress response and does not compromise animal welfare.

Inhibitory and facilitatory connectivity from ventral premotor to primary motor cortex in healthy humans at rest--a bifocal TMS study.

Sex differences in descending control of nociception (DCN) responses after chronic orofacial pain induction in rats and the contribution of kappa opioid receptors

BackgroundConditioned pain modulation (CPM) evaluates the effect of a painful conditioning stimulus (CS) on a painful test stimulus (TS). Using painful cutaneous electrical stimulation (PCES) as TS and painful cold water as CS, the pain relief was paralleled by a decrease in evoked potentials (PCES-EPs). We now aimed to compare the effect of CPM with cognitive distraction on PCES-induced pain and PCES-EP amplitudes.MethodsPCES was performed using surface electrodes inducing a painful sensation of 60 (NRS 0–100) on one hand. In a crossover design healthy subjects (included: n = 38, analyzed: n = 23) immersed the contralateral hand into 10 °C cold water (CS) for CPM evaluation and performed the 1-back task for cognitive distraction. Before and during the CS and 1-back task, respectively, subjects rated the pain intensity of PCES and simultaneously cortical evoked potentials were recorded.ResultsBoth CPM and cognitive distraction significantly reduced PCES-EP amplitudes (CPM: 27.6 ± 12.0 μV to 20.2 ± 9.5 μV, cognitive distraction: 30.3 ± 14.2 µV to 13.6 ± 5.2 μV, p < 0.001) and PCES-induced pain (on a 0–100 numerical rating scale: CPM: 58 ± 4 to 41.1 ± 12.3, cognitive distraction: 58.3 ± 4.4 to 38.0 ± 13.0, p < 0.001), though the changes in pain intensity and PCES-amplitude did not correlate. The changes of the PCES-EP amplitudes during cognitive distraction were more pronounced than during CPM (p = 0.001).ConclusionsCPM and cognitive distraction reduced the PCES-induced pain to a similar extent. The more pronounced decrease of PCES-EP amplitudes after distraction by a cognitive task implies that both conditions might not represent the general pain modulatory capacity of individuals, but may underlie different neuronal mechanisms with the final common pathway of perceived pain reduction.

The ocular following responses elicited by brief unexpected movements of the visual scene were studied in eight rhesus monkeys. Test patterns were random dots except in one experiment when sine-wave gratings were used. Test stimuli were velocity steps of 100-ms duration applied after spontaneous saccades. Two response measures were used: the initial peak in the eye velocity profile (ei), and the average final eye velocity over the period of 110-140 ms measured from stimulus onset (ef). Responses were best when the test ramps began soon after saccades and attenuated progressively as the postsaccadic delay interval was increased: postsaccadic enhancement of ocular following. The decline in ei was roughly exponential: average time constant, 60 ms; average asymptote, 22%. Later measures (ef) were generally less affected. We suggest that this transient enhancement aids the visual suppression of postsaccadic ocular drifts (glissades) and the tracking of moving images newly acquired with a saccade. The magnitude of the postsaccadic enhancement was dependent on the amount of retinal stimulation during the antecedent saccade; when this stimulation was compromised, as when a vertical saccade was made while viewing a grating pattern with vertically oriented stripes, subsequent enhancement of ocular following was much reduced. Further, saccade-like conditioning movements of the visual scene resulted in an enhancement of the ocular following, elicited by subsequent test ramps, that was similar in magnitude and time course to that in the wake of real saccades. We conclude that the postsaccadic enhancement of ocular following is largely due to the visual stimulation produced by the saccade sweeping the scene across the retina. Data obtained with the visual field partitioned into central and peripheral regions (center 20-60 degrees diam) and with gaze centered suggested that the short-latency ocular following system and the enhancement mechanism that modulates it both receive their major inputs from the central 40 degrees of the retina. Further, when this central region was partitioned, enhancement was obtained only when the conditioning and test stimuli were presented to the same region of retina. Visual enhancement showed only weak interocular transfer: the conditioning and test stimuli had to be seen by the same eye to produce appreciable enhancement. These data suggest that the enhancement involves local spatial interactions at an "early" point in the visual pathway before the inputs from the two eyes have converged. When the conditioning and test stimuli impinged on different regions of the retina, brief powerful suppression of ocular following was obtained.(ABSTRACT TRUNCATED AT 400 WORDS)

Extra- and intracellular recordings from the CA1 region of rat hippocampal slices were employed to examine the role of the slow afterhyperpolarization (sAHP) in modulating the increases in neuronal excitability observed on increasing extracellular pH (pHo) from 7.4 to 7.7. In the majority of experiments, an antidromic conditioning stimulus applied in the presence of D(-)-2-amino-5-phosphonopentanoic acid (D-APV), 6-cyano-7-nitroquinoxaline-2,3-dione disodium salt (CNQX) and bicuculline was employed to elicit a sAHP, and an antidromic test stimulus was applied during the sAHP. At pHo 7.4, a single conditioning stimulus elicited an action potential followed by a sAHP, which in turn inhibited the response to the test stimulus compared with the conditioning stimulus. Increasing the number of action potentials in the conditioning stimulus augmented the sAHP and further inhibited the test response, whereas isoproterenol inhibited the sAHP and prevented the relative inhibition of the test response. At pHo 7.7, a single conditioning stimulus elicited a burst of action potentials followed by a large sAHP, which in turn prevented the test stimulus from eliciting a burst of action potentials and, in extracellular recordings, further increased the inhibition of the test response. The latter effect did not solely reflect a high pHo-induced increase in the conditioning response (and, thus, the subsequent sAHP), but rather involved a more direct effect of high pHo to augment the sAHP. The results indicate that increasing pHo increases the excitability of CA1 neurons to an initial stimulus; however, a high pHo-dependent increase in the sAHP evoked by the initial stimulus limits the response to subsequent stimuli.

When investigating the role of facilitatory and inhibitory pain mechanisms such as conditioned pain modulation (CPM) and temporal summation of pain (TSP), it is important to take both into consideration in a single experimental model to provide the most information on subgroups of patients. Therefore, the objective of this study was to identify subgroups in a large population of pediatric patients with chronic pain based on their facilitatory and inhibitory pain mechanisms and compare them with control subjects. Five hundred twenty-one female subjects and 147 male subjects between 8 and 21 years old underwent a CPM assessment using a 2-minute tonic noxious heat stimulation as the test stimulus and a 2-minute cold-pressor task (CPT) (12°C) as the conditioning stimulus. The best partition of clusters of patients was 3 clusters accounting for 27.15% of the total variation in the data. Cluster 1 (n = 271) was best characterized by high pain intensity during the CPT, lack of TSP during the test stimuli, and efficient inhibitory CPM. Cluster 2 (n = 186) was best characterized by low pain intensity during the CPT, lack of TSP during the test stimuli, and efficient inhibitory CPM. Cluster 3 (n = 151) was best characterized by high pain intensity during the CPT, presence of TSP during the test stimuli, and inefficient inhibitory CPM. A single thermal CPM experimental design can identify combinations of facilitatory and inhibitory pain modulation responses. Findings from the current study add to the literature by describing different clinical phenotypes of central pain mechanisms of youth with chronic pain.

Despite extensive research on conditioned pain modulation (CPM), uncertainties remain regarding the role of cognitive mechanisms, such as attentional focus, distraction, and intrinsic a priori expectations, and the most optimal CPM protocol design (parallel vs. sequential). This study examined whether these cognitive factors influence CPM efficacy, and whether CPM magnitude differs between a parallel and sequential protocol. Seventy-two healthy adults participated in this randomised cross-over study undergoing CPM evaluation, that is, pain pressure threshold assessment (=test stimulus) in response to hot water immersion (=conditioning stimulus (CS)) during four experimental protocols, that is, a neutral parallel protocol, a neutral sequential protocol, a sequential protocol with attentional focus on the CS-induced pain intensity, and a sequential protocol with attentional distraction from the CS. Pain expectations were recorded before each protocol. Focusing attention on the CS during CPM assessment resulted in smaller CPM magnitudes compared to no attentional manipulation or distracting from the CS. Distracting from the CS did not affect CPM magnitude compared to no attentional manipulation, nor did a priori expectations. Although CPM magnitudes were not statistically different between the parallel and sequential CPM protocol, a sequential protocol provides higher mean magnitudes and responder rates. Since attentional focus on the CS reduces CPM efficacy, it is recommended to not rate the CS pain intensity during CS application to prevent a reduction of the inhibitory effect. Furthermore, a sequential protocol is recommended over a parallel protocol as a 'cleaner' representation of pain modulation free of attentional sources of biases. Conditioned pain modulation (CPM) is an important biomarker reflecting pain processing, however, there is a high variability in CPM response, making it important to gain insight into the influencing factors and mechanisms of CPM. The results of this study suggest that attentional focus on the conditioning stimulus influences CPM magnitude, whereas a distraction task and intrinsic a priori expectations do not. In both therapeutic and preventive approaches, it is of great interest for clinicians to positively address factors influencing CPM. ClinicalTrials.gov identifier: NCT05161286.