There was few human study evaluated the analgesic effect of acupuncture on central nervous system (CNS). The electrical temporal summation (TS) pain model has been validated and provides the opportunity to study the central inhibition effect of acupuncture in healthy humans. The present study aimed to: 1. systematically review available randomised, controlled trials (RCTs) of acupuncture on experimentally induced pain in healthy humans; 2. conduct a RCT to assess the effect of manual acupuncture (MA) and electro-acupuncture (EA) on TS of pain and the spatial (i.e. the local and remote sites to acupuncture stimulation) and the temporal (i.e. immediately after and 24-hours after the intervention) characteristics of this effect. The systematic review was carried out in accordance with the requirements of a Cochrane Systematic Review. The methodological quality and credibility of the acupuncture intervention of the included RCTs were assessed. The Review Management software (RevMan version 4.2, The Cochrane Library) was used for data extraction and data analysis. 605 papers were identified from four databases (Pubmed, Cochrane Library, CINAHL and EMBASE). Only nine papers met the inclusion criteria. The methodological quality and credibility of the acupuncture invention were satisfactory. The pain models and interventions applied varied substantially from study to study. Consequently, meta-analyses were not conducted. Comparing acupuncture with non-invasive control, significant acupuncture analgesia was reported. These studies also demonstrated that invasive controls produced analgesia. For the RCT of acupuncture on TS, 27 healthy volunteers were recruited and randomly assigned to either EA, MA or sham-acupuncture (SA) group, with nine volunteers in each group. To test pain thresholds, transcutaneous electrical stimulation was delivered to two sites on the anterior aspects of both legs and one site on the dorsum of the non-dominant forearm. Pain thresholds to single electrical stimulation (SPT) and to TS stimulation (TST) were assessed before, 30-minutes after and 24-hours after the intervention. Acupuncture was given to Zusanli (ST36) and Fenglong (ST 40) on the dominant leg. The level of anxiety was assessed before and after acupuncture with Spielberg State and Anxiety Inventory. The three groups were comparable at baseline. The level of anxiety did not change significantly after acupuncture. EA significantly increased SPT and TST on the treatment leg 24-hour after the treatment when compared with SA (p less than 0.05), but did not increase those measured on the non-treatment leg or the forearm. The fact that such an effect increased within 24 hours after acupuncture might indicate the potential role of neurohumoral mechanisms in acupuncture analgesia. The analgesia effect of EA on TS tended to be localised at the needling site. This observation is different from the understanding of the wide-spread effect of acupuncture. The discrepancy could be due to the small sample size of the current study. In conclusion, this is the first study that demonstrates EA elicits a strong inhibition on the CNS in health humans. Such a central effect lasts more than 24 hours, and limits to the site where acupuncture is applied. These findings need to be confirmed in other TS models.

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No description available.

Adverse childhood events have been identified as a risk factor for developing chronic pain conditions in adulthood. However, previous studies have inconsistently supported the link between adverse childhood events and hypersensitivity to laboratory-induced pain. Therefore, this study intended to investigate the effects of adverse childhood events on temporal summation of second pain (TSSP). A group of 38 healthy and pain-free college students participated in laboratory pain tests after being screened for childhood trauma history. Half of participants (47.5% female) were positive for childhood trauma and the other half (63.2% female) reported no adverse childhood event. The laboratory pain tests measured TSSP using 10 thermal pulses per trial over four consecutive trials. The trauma group showed a tendency of greater sensitization within TSSP trials and lack of habituation over repeated TSSP trials. In sum, adverse childhood events predisposed adults to enhanced TSSP, which is potentially linked to an increased likelihood to develop chronic pain problems.

No description available.

<p>In order to understand how the brain functions, under normal as well as pathological conditions, it is important to study the mechanisms underlying information integration. Depending on the nature of an input arriving at a synapse, different strategies may be used by the neuron to integrate and respond to the input. Naturally, if a short train of high-frequency synaptic input arrives, it may be beneficial for the neuron to be equipped with a fast mechanism that is highly sensitive to inputs on a short time scale. If, on the contrary, inputs arriving with low frequency are to be processed, it may be necessary for the neuron to possess slow mechanisms of integration. For example, in certain working memory tasks (e. g. delay-match-to-sample), sensory inputs may arrive separated by silent intervals in the range of seconds, and the subject should respond if the current input is identical to the preceeding input. It has been suggested that single neurons, due to intrinsic mechanisms outlasting the duration of input, may be able to perform such calculations. In this work, I have studied a mechanism thought to be particularly important in supporting the integration of low-frequency synaptic inputs. It is mediated by a cascade of events that starts with activation of group I metabotropic glutamate receptors (mGlu1/5), and ends with a membrane depolarization caused by a current that is mediated by canonical transient receptor potential (TRPC) ion channels. This current, denoted I_TRPC, is the focus of this thesis.</p><p>A specific objective of this thesis is to study the role of I_TRPC in the integration of synaptic inputs arriving at a low frequency, < 10 Hz. Our hypothesis is that, in contrast to the well-studied, rapidly decaying AMPA and NMDA currents, I_TRPC is well-suited for supporting temporal summation of such synaptic input. The reason for choosing this range of frequencies is that neurons often communicate with signals (spikes) around 8 Hz, as shown by single-unit recordings in behaving animals. This is true for several regions of the brain, including the entorhinal cortex (EC) which is known to play a key role in producing working memory function and enabling long-term memory formation in the hippocampus.</p><p>Although there is strong evidence suggesting that I_TRPC is important for neuronal communication, I have not encountered a systematic study of how this current contributes to synaptic integration. Since it is difficult to directly measure the electrical activity in dendritic branches using experimental techniques, I use computational modeling for this purpose. I implemented the components necessary for studying I_TRPC, including a detailed model of extrasynaptic glutamate concentration, mGlu1/5 dynamics and the TRPC channel itself. I tuned the model to replicate electrophysiological in vitro data from pyramidal neurons of the rodent EC, provided by our experimental collaborator. Since we were interested in the role of I_TRPC in temporal summation, a specific aim was to study how its decay time constant (τ_decay) is affected by synaptic stimulus parameters.</p><p>The hypothesis described above is supported by our simulation results, as we show that synaptic inputs arriving at frequencies as low as 3 - 4 Hz can be effectively summed. We also show that τ_decay increases with increasing stimulus duration and frequency, and that it is linearly dependent on the maximal glutamate concentration. Under some circumstances it was problematic to directly measure τ_decay, and we then used a pair-pulse paradigm to get an indirect estimate of τ_decay.</p><p>I am not aware of any computational model work taking into account the synaptically evoked I_TRPC current, prior to the current study, and believe that it is the first of its kind. We suggest that I_TRPC is important for slow synaptic integration, not only in the EC, but in several cortical and subcortical regions that contain mGlu1/5 and TRPC subunits, such as the prefrontal cortex. I will argue that this is further supported by studies using pharmacological blockers as well as studies on genetically modified animals.</p> / QC 20101005

In order to understand how the brain functions, under normal as well as pathological conditions, it is important to study the mechanisms underlying information integration. Depending on the nature of an input arriving at a synapse, different strategies may be used by the neuron to integrate and respond to the input. Naturally, if a short train of high-frequency synaptic input arrives, it may be beneficial for the neuron to be equipped with a fast mechanism that is highly sensitive to inputs on a short time scale. If, on the contrary, inputs arriving with low frequency are to be processed, it may be necessary for the neuron to possess slow mechanisms of integration. For example, in certain working memory tasks (e. g. delay-match-to-sample), sensory inputs may arrive separated by silent intervals in the range of seconds, and the subject should respond if the current input is identical to the preceeding input. It has been suggested that single neurons, due to intrinsic mechanisms outlasting the duration of input, may be able to perform such calculations. In this work, I have studied a mechanism thought to be particularly important in supporting the integration of low-frequency synaptic inputs. It is mediated by a cascade of events that starts with activation of group I metabotropic glutamate receptors (mGlu1/5), and ends with a membrane depolarization caused by a current that is mediated by canonical transient receptor potential (TRPC) ion channels. This current, denoted ITRPC, is the focus of this thesis. A specific objective of this thesis is to study the role of ITRPC in the integration of synaptic inputs arriving at a low frequency, &lt; 10 Hz. Our hypothesis is that, in contrast to the well-studied, rapidly decaying AMPA and NMDA currents, ITRPC is well-suited for supporting temporal summation of such synaptic input. The reason for choosing this range of frequencies is that neurons often communicate with signals (spikes) around 8 Hz, as shown by single-unit recordings in behaving animals. This is true for several regions of the brain, including the entorhinal cortex (EC) which is known to play a key role in producing working memory function and enabling long-term memory formation in the hippocampus. Although there is strong evidence suggesting that ITRPC is important for neuronal communication, I have not encountered a systematic study of how this current contributes to synaptic integration. Since it is difficult to directly measure the electrical activity in dendritic branches using experimental techniques, I use computational modeling for this purpose. I implemented the components necessary for studying ITRPC, including a detailed model of extrasynaptic glutamate concentration, mGlu1/5 dynamics and the TRPC channel itself. I tuned the model to replicate electrophysiological in vitro data from pyramidal neurons of the rodent EC, provided by our experimental collaborator. Since we were interested in the role of ITRPC in temporal summation, a specific aim was to study how its decay time constant (τdecay) is affected by synaptic stimulus parameters. The hypothesis described above is supported by our simulation results, as we show that synaptic inputs arriving at frequencies as low as 3 - 4 Hz can be effectively summed. We also show that τdecay increases with increasing stimulus duration and frequency, and that it is linearly dependent on the maximal glutamate concentration. Under some circumstances it was problematic to directly measure τdecay, and we then used a pair-pulse paradigm to get an indirect estimate of τdecay. I am not aware of any computational model work taking into account the synaptically evoked ITRPC current, prior to the current study, and believe that it is the first of its kind. We suggest that ITRPC is important for slow synaptic integration, not only in the EC, but in several cortical and subcortical regions that contain mGlu1/5 and TRPC subunits, such as the prefrontal cortex. I will argue that this is further supported by studies using pharmacological blockers as well as studies on genetically modified animals. / QC 20101005

Introduction : L’altération des systèmes de récompense et de douleur serait impliquée dans le développement et le maintien de la douleur chronique. En contexte expérimental, l’arrêt d’une stimulation douloureuse et désagréable peut déclencher une sensation de plaisir (pleasant pain relief, PPR), mais contrairement aux mécanismes endogène d’inhibition de douleur (ICPM) la variabilité interindividuelle du PPR semble ne jamais avoir été étudiée. Objectifs : Étude 1) Investiguer la variabilité interindividuelle du PPR et de l’ICPM chez des sous-groupes de sujets sains ayant des réponses de douleur dynamiques similaires (analyses de trajectoires) durant un test à l’eau froide (CPT) Étude 2) Mesurer la connectivité au repos de régions du système de récompense en IRMf en lien avec le PPR. Méthode : 1) Une thermode Peltier et un CPT (10 ℃) ont été administrés séquentiellement (N=122). Le PPR a été mesuré pendant quatre minutes après l’arrêt du CPT et, 2) suite à l’application d’un gel froid en imagerie fonctionnelle (N=38). Résultats : 1) Quatre trajectoires ont été identifiées selon les réponses de douleur durant le CPT. Le PPR était corrélé aux trajectoires de douleur, mais pas l’efficacité d’ICPM. 2) Les connexions au repos, significativement corrélées au PPR, étaient les suivantes : noyau accumbens (NAcc) gauche-cortex cingulaire postérieur, NAcc gauche-cortex cingulaire antérieur dorsal, amygdale gauche-cortex préfrontal dorsolatéral, NAcc droit-cervelet crus II gauche et droit et cortex préfrontal ventromédian-cervelet crus II droit. Discussion : La sensibilisation et l’aspect désagréable moyen de douleur durant une stimulation nociceptive tonique ainsi que la connectivité au repos entre des régions modulant le plaisir (récompense) et la cognition affectent le degré de PPR. / Introduction: Alteration of reward and pain systems is related to the development of chronic pain. In experimental settings, the cessation of a painful and unpleasant stimulation has been shown to elicit a pleasant pain relief (PPR), but contrary to inhibitory conditioned pain modulation mechanisms (ICPM) inter-individual variability of PPR appears to have never been studied. Objectives: Study 1) Investigate inter-individual variability of PPR and ICPM in subgroups of healthy subjects with similar dynamic pain responses (trajectory analyses) during a cold pressor test (CPT) Study 2) Measure resting state functional connectivity with regions of the reward system related to PPR. Method: 1) Peltier thermode and CPT (10℃) were administered sequentially (N=122). The PPR was measured for four minutes after CPT offset 2) PPR was measured (N=38) following the application of a cold gel during functional imaging. Results: 1) Four trajectories were identified based on pain responses during CPT. PPR was correlated with pain trajectories, but not the efficacy of ICPM. 2) Resting state connections, significantly correlated with PPR, were the following: left nucleus accumbens (NAcc)-posterior cingulate cortex, left NAcc-dorsal anterior cingulate cortex, left amygdala-dorsolateral prefrontal cortex, right NAcc-left and right cerebellum crus II and ventromedial prefrontal cortex-right cerebellum crus II. Discussion: Sensitization and average pain unpleasantness during tonic nociceptive stimulation, as well as connectivity between regions modulating pleasure (reward) and cognition, affect the degree of PPR.

The moment-to-moment fluctuations in pain-evoked sensory and emotional qualities, and how the pain experience differs between sexes are not well understood. Therefore, this thesis sought to 1) characterise the temporal profiles of the most prominent noxious heat-evoked sensations, 2) characterise sex differences in these sensations, 3) evaluate the magnitude of sharp pain quality evoked in hairy and glabrous skin, and 4) determine the role of absolute stimulus temperatures on sex differences in pain adaptation and habituation. A broad-based heat pain model was developed for this study that incorporates a temporally-continuous assessment of multiple sensory and affective pain dimensions, including pain, burning, sharp, stinging, cutting, and annoyance evoked by two types (static, dynamic) of repeated prolonged noxious heat stimuli. The salient hypotheses were: 1) Burning sensations have a different temporal profile compared with sharp and other related qualities, 2) The temporal dynamics of heat pain intensity and annoyance differ between males and females, 3) Sex differences in heat pain are associated with specific pain qualities and specific types of skin, and 4) Moderate-high temperatures induce pain adaptation and habituation in females but not in males. The most prominent findings were 1) sharp, stinging and cutting sensations adapted when stimulus intensity was static, but burning sensations were evoked during static and dynamic stimulus phases, 2) pain and annoyance in women were greater than men during the dynamic phases of the first stimulus but less than men during static stimulus phases and on stimulus repetition, 3) the sex difference in pain adaptation occurred with percept-fixed stimulus intensities and with absolute stimulus temperatures, 4) the sex effects associated with dynamic stimuli occurred in hairy but not glabrous skin. These findings give new insights into the relationships between pain intensity, quality and affect and have strong implications for views on sex differences in pain sensitivity.

The moment-to-moment fluctuations in pain-evoked sensory and emotional qualities, and how the pain experience differs between sexes are not well understood. Therefore, this thesis sought to 1) characterise the temporal profiles of the most prominent noxious heat-evoked sensations, 2) characterise sex differences in these sensations, 3) evaluate the magnitude of sharp pain quality evoked in hairy and glabrous skin, and 4) determine the role of absolute stimulus temperatures on sex differences in pain adaptation and habituation. A broad-based heat pain model was developed for this study that incorporates a temporally-continuous assessment of multiple sensory and affective pain dimensions, including pain, burning, sharp, stinging, cutting, and annoyance evoked by two types (static, dynamic) of repeated prolonged noxious heat stimuli. The salient hypotheses were: 1) Burning sensations have a different temporal profile compared with sharp and other related qualities, 2) The temporal dynamics of heat pain intensity and annoyance differ between males and females, 3) Sex differences in heat pain are associated with specific pain qualities and specific types of skin, and 4) Moderate-high temperatures induce pain adaptation and habituation in females but not in males. The most prominent findings were 1) sharp, stinging and cutting sensations adapted when stimulus intensity was static, but burning sensations were evoked during static and dynamic stimulus phases, 2) pain and annoyance in women were greater than men during the dynamic phases of the first stimulus but less than men during static stimulus phases and on stimulus repetition, 3) the sex difference in pain adaptation occurred with percept-fixed stimulus intensities and with absolute stimulus temperatures, 4) the sex effects associated with dynamic stimuli occurred in hairy but not glabrous skin. These findings give new insights into the relationships between pain intensity, quality and affect and have strong implications for views on sex differences in pain sensitivity.