Repetitive Mechanical Stimuli Research Articles

Neural oscillatory markers of respiratory sensory gating in human cortices

BackgroundHuman respiratory sensory gating is a neural process associated with inhibiting the cortical processing of repetitive respiratory mechanical stimuli. While this gating is typically examined in the time domain, the neural oscillatory dynamics, which could offer supplementary insights into respiratory sensory gating, remain unknown. The purpose of the present study was to investigate central neural gating of respiratory sensation using both time- and frequency-domain analyses. MethodsA total of 37 healthy adults participated in this study. Two transient inspiratory occlusions were presented within one inspiration, while responses in the electroencephalogram (EEG) were recorded. N1 amplitudes and oscillatory activities to the first stimulus (S1) and the second stimulus (S2) were measured. The perceived level of breathlessness and level of unpleasantness elicited by the occlusions were measured after the experiment. ResultsAs expected, the N1 peak amplitude to the S1 was significantly larger than to the S2. The averaged respiratory sensory gating S2/S1 ratio for the N1 peak amplitude was 0.71. For both the evoked- and induced-oscillations, time-frequency analysis showed higher theta activations in response to S1 relative to S2. A positive correlation was observed between the perceived unpleasantness and induced theta power. ConclusionsOur results suggest that theta oscillations, evoked as well as induced, reflect the “gating” of respiratory sensation. Theta oscillation, particularly theta induced power, may be indicative of emotional processing of respiratory mechanosensation. The findings of this study serve as a foundation for future investigations into the underlying mechanisms of respiratory sensory gating, particularly in patient populations.

Sustainable mechanochemical growth of double-network hydrogels supported by vascular-like perfusion.

Double-network (DN) gels are unique mechanochemical materials owing to their structures that can be dynamically remodelled during use. The mechanical energy applied to DN gels is efficiently transferred to the chemical bonds of the brittle network, generating mechanoradicals that initiate the polymerisation of pre-loaded monomers, thereby remodelling the materials. To attain continuous remodelling or growth in response to repetitive mechanical stimuli, a sustainable supply of chemical reagents to such dynamic materials is essential. In this study, inspired by the vascular perfusion transporting nutrients to cells, we constructed a circulatory system for a continuous supply of chemicals to channel-containing DN hydrogels (c-DN gels). The perfusion of monomer solutions through the channel and permeability of the c-DN gels not only replenishes the monomers consumed by the polymerisation but also replenishes the water loss caused by the surface evaporation of hydrogel, thereby freeing the mechanochemical process of DN gels from the constraints of the underwater environment. The facile chemical supply enabled us to modulate the mechanical enhancement of the c-DN gel and attain muscle-like strengthening under repeated mechanical training in deoxygenated air. We also studied the kinetics of polymer growth and strengthening and deciphered unique features of mechanochemical reaction in DN gels including the extremely long-living radicals and delayed mechanical strengthening.

The impact of emotional context on neural substrates of respiratory sensory gating.

Psychological challenges have been found to impact respiratory symptom perception in healthy individuals as well as in patients with various neurological disorders. Human respiratory sensory gating is an objective measure to examine respiratory sensory information processing of repetitive respiratory mechanical stimuli in the central nervous system. With this electrophysiological method, patients with higher anxiety levels showed reduced respiratory sensory gating function in the cortex, and increased symptom perception. In addition, positive emotional contexts were found to increase the respiratory sensory gating function using RREPs. However, neural substrates related to emotional impacts on respiratory sensory gating remain still unclear. In the present study, we examined the emotion processing of respiratory sensory gating using functional magnetic resonance imaging. We hypothesized that positive compared with neutral stimuli would result in reduced brain activations in cortical areas with the paired occlusion paradigm. Thirty-five healthy adults participated in this event-designed fMRI experiment. Paired inspiratory occlusions (two transient occlusions with a 500 ms inter-stimulus-interval are delivered during one inspiration) were provided using an external trigger outside of the scanner. At least 40 paired inspiratory occlusions were collected for each trial. The experiment contained three runs during which participants underwent 12 min for the paired inspiratory occlusion paradigm while watching a fixation cross (the control condition), neutral and positive emotional picture series. The order of emotional picture series was randomized across the participants. Our results revealed an overall trend of reduction of brain activity from the neutral (minus fixation) condition, to the pleasant (minus fixation) condition. For bilateral thalamus and primary visual cortices, there was no significant difference in neural activation between the two contrasts of pleasant (ContrastP-F) and neutral condition (ContrastN-F). The activation of the mid-cingulate and the orbitofrontal cortex was lower in ContrastP-F compared to ContrastN-F. In conclusion, our results suggest that emotional context, especially positive valence, modulates neural correlates in middle cingulate cortex and orbitofrontal cortex in terms of respiratory sensory gating. Future studies are recommended to test emotional impacts on respiratory sensations in patients with neurological disorders.

Mechanical temporal summation is associated with greater muscle co-contraction during walking in knee osteoarthritis

Purpose: People with knee osteoarthritis (OA) walk with altered motor patterns, including excessive muscular co-contraction, that can lead to disease worsening. Factors related to increased muscular co-contraction during walking in people with knee OA are not well known, but one is suggested to be pain sensitization. An abnormally augmented pain response to repetitive mechanical stimuli can be present in people with chronic pain. Mechanical loading during activities like walking could activate peripheral and central nociceptive pathways ; if the central nervous system is sensitized, it is possible that could then affect motor function leading to altered muscle activity.

Structural Response of the Piezo Channel to Force Application at Different Frequencies

Piezo proteins are the major mechanosensitive ion channels in mammalians that translate the mechanical cues into electrical signals. Recent functional studies have revealed they act as frequency filters of repetitive mechanical stimuli. However, a structural view of the channel's response upon exposure to repetitive force at various frequencies remains elusive. Previously, we demonstrated that high-speed atomic force microscopy (HS-AFM) is an excellent tool to visualize the force-induced conformational changes in Piezo1.

Inactivation of Mechanically Activated Piezo1 Ion Channels Is Determined by the C-Terminal Extracellular Domain and the Inner Pore Helix

SUMMARYPiezo proteins form mechanically activated ion channels that are responsible for our sense of light touch, proprioception, and vascular blood flow. Upon activation by mechanical stimuli, Piezo channels rapidly inactivate in a voltage-dependent manner through an unknown mechanism. Inactivation of Piezo channels is physiologically important, as it modulates overall mechanical sensitivity, gives rise to frequency filtering of repetitive mechanical stimuli, and is itself the target of numerous human disease-related channelopathies that are not well understood mechanistically. Here, we identify the globular C-terminal extracellular domain as a structure that is sufficient to confer the time course of inactivation and a single positively charged lysine residue at the adjacent inner pore helix as being required for its voltage dependence. Our results are consistent with a mechanism for inactivation that is mediated through voltage-dependent conformations of the inner pore helix and allosteric coupling with the C-terminal extracellular domain.

Transduction of Repetitive Mechanical Stimuli by Piezo1 and Piezo2 Ion Channels

Several cell types experience repetitive mechanical stimuli, including vein endothelial cells during pulsating blood flow, inner ear hair cells upon sound exposure, and skin cells and their innervating dorsal root ganglion (DRG) neurons when sweeping across a textured surface or touching a vibrating object. While mechanosensitive Piezo ion channels have been clearly implicated in sensing static touch, their roles in transducing repetitive stimulations are less clear. Here, we perform electrophysiological recordings of heterologously expressed mouse Piezo1 and Piezo2 responding to repetitive mechanical stimulations. We find that both channels function as pronounced frequency filters whose transduction efficiencies vary with stimulus frequency, waveform, and duration. We then use numerical simulations and human disease-related point mutations to demonstrate that channel inactivation is the molecular mechanism underlying frequency filtering and further show that frequency filtering is conserved in rapidly adapting mouse DRG neurons. Our results give insight into the potential contributions of Piezos in transducing repetitive mechanical stimuli.

Flexible cell culture device made of membrane-type silicone composites for simulating human body

Human tissues are exposed to various mechanical stimuli, and the types and magnitudes of the mechanical stimuli acting on cells and tissues are important factors in controlling the development pathway of cells and tissues. Therefore, giving repetitive mechanical stimuli to culturing cells may provide beneficial effects, such as differentiating target cells or accelerating cell development, by controlling the type of stimulus and its magnitude. Electroactive polymers (EAPs) respond to electrical voltage with significant changes in shape or size and can transfer appropriate (1–20%) mechanical stimuli to cells. In this study, we designed a new type of flexible cell culture device made of silicone (composite) film, and evaluated the actuating strain of the driving portion of the cell culture device according to the pre-stretching condition and the clay nanoparticle (i.e., organically modified montmorillonite, or OMMT) content. The effect of OMMT particles on the electro-mechanical performance of the silicone (composite) film actuators was investigated by adding 0–5% OMMT particles to silicone elastomer using the solvent-assisted mixing method. The effects of these two major variables on actuation strain were quantitatively investigated, and the most appropriate conditions for the driving part of a cell culture device were determined.

Evoked temporal summation in cats to highlight central sensitization related to osteoarthritis-associated chronic pain: a preliminary study.

In cats, osteoarthritis causes significant chronic pain. Chronicity of pain is associated with changes in the central nervous system related to central sensitization, which have to be quantified. Our objectives were 1) to develop a quantitative sensory testing device in cats for applying repetitive mechanical stimuli that would evoke temporal summation; 2) to determine the sensitivity of this test to osteoarthritis-associated pain, and 3) to examine the possible correlation between the quantitative sensory testing and assessment using other pain evaluation methods. We hypothesized that mechanical sub-threshold repetitive stimuli would evoke temporal summation, and that cats with osteoarthritis would show a faster response. A blinded longitudinal study was performed in 4 non-osteoarthritis cats and 10 cats with naturally occurring osteoarthritis. Quantification of chronic osteoarthritis pain-related disability was performed over a two week period using peak vertical force kinetic measurement, motor activity intensity assessment and von Frey anesthesiometer-induced paw withdrawal threshold testing. The cats afflicted with osteoarthritis demonstrated characteristic findings consistent with osteoarthritis-associated chronic pain. After a 14-day acclimation period, repetitive mechanical sub-threshold stimuli were applied using a purpose-developed device. Four stimulation profiles of predetermined intensity, duration and time interval were applied randomly four times during a four-day period. The stimulation profiles were different (P<0.001): the higher the intensity of the stimulus, the sooner it produced a consistent painful response. The cats afflicted with osteoarthritis responded more rapidly than cats osteoarthritis free (P = 0.019). There was a positive correlation between the von Frey anesthesiometer-induced paw withdrawal threshold and the response to stimulation profiles #2 (2N/0.4 Hz) and #4 (2N/0.4 Hz): Rhos = 0.64 (P = 0.01) and 0.63 (P = 0.02) respectively. This study is the first report of mechanical temporal summation in awake cats. Our results suggest that central sensitization develops in cats with naturally occurring osteoarthritis, providing an opportunity to improve translational research in osteoarthritis-associated chronic pain.

I Am Touched by Your Pain: Limb-Specific Modulation of the Cortical Response to a Tactile Stimulation During Pain Observation

The observation of pain in other individuals is known to impact the cerebral activity in regions dedicated to one’s nociception, as well as the behavior toward the person in pain. However, it remains unclear whether this shared representation for pain modulates somatosensory processing to nonpainful stimuli and whether this modulation is limb specific. Twenty right-handed healthy participants viewed a series of pictures depicting right hands or right feet in painful or nonpainful situations while light repetitive (25 Hz) mechanical stimuli were applied to the hand. The cortical excitability to these nonpainful stimuli was measured through the energy in the 25-Hz frequency band of electroencephalographic data. Following picture onset, a combination of nonspecific and specific modulation of cortical excitability was found. The former was widespread over the parieto-central region and likely related to factors such as attention. The latter was mostly restricted to 3 electrodes over the parietal cortex contralateral to the stimulation of the hand, and was specifically associated with the observation of others’ hand in painful scenarios. This result confirms that the observation of pain can modulate somatosensory cortical excitability in an effector-specific way. The findings add to the accumulating evidence that other people’s somatic pain is mapped onto the observer’s sensori-motor system and offers a new paradigm to investigate potential neurophysiological changes in care providers who are often overexposed to others' pain. Perspective This electroencephalography study demonstrates with a quick, easily implementable, and noninvasive paradigm that the change in cortical somatosensory excitability during pain observation is limb-specific, and confirms from a neuroscience perspective that being exposed to others’ pain implies more than the sharing of an affective experience.

Elevated Pain Sensitivity in Chronic Pain Patients at Risk for Opioid Misuse

This study employed quantitative sensory testing (QST) to evaluate pain responses in chronic spinal pain patients at low risk and high risk for opioid misuse, with risk classification based on scores on the Screener and Opioid Assessment for Patients with Pain-Revised (SOAPP-R). Patients were further subgrouped according to current use of prescription opioids. Of the 276 chronic pain patients tested, approximately 65% were taking opioids; a median split was used to further categorize these patients as being on lower or higher doses of opioids. The high-risk group (n = 161) reported higher levels of clinical pain, had lower pressure and thermal pain thresholds at multiple body sites, had lower heat pain tolerance, and rated repetitive mechanical stimuli as more painful relative to the low-risk group (n = 115; P’s < .01). In contrast, QST measures did not differ across opioid groups. Multiple linear regression analysis suggested that indices of pain-related distress (ie, anxiety and catastrophizing about pain) were also predictive of hyperalgesia, particularly in patients taking opioids. Collectively, regardless of opioid status, the high-risk group was hyperalgesic relative to the low-risk group; future opioid treatment studies may benefit from the classification of opioid risk, and the examination of pain sensitivity and other factors that differentiate high- and low-risk groups. Perspective This study demonstrates that chronic spinal pain patients at high risk for misuse of prescription opioids are more pain-sensitive than low-risk patients, whether or not they are currently taking opioids. Indices of pain-related distress were important predictors of pain sensitivity, particularly among those patients taking opioids for pain.

Intrinsic membrane properties of spinal dorsal horn neurones modulate nociceptive information processingin vivo

The dorsal horn of the spinal cord is the first central relay where nociceptive inputs are processed. Based on the expression and modulation of intrinsic electrophysiological properties in in vitro slice preparations, dorsal horn neurones (DHNs) display different discharge patterns (tonic, plateau or rhythmic), which shape the neurone's response to sensory inputs. However, it is unclear whether intrinsic properties play any role in sensory processing in vivo. Using in vivo patch clamp recordings in the adult rat, we here examine whether these intrinsic properties are present, and to what extent they determine the DHN response to natural stimulation. We focused primarily on wide dynamic range neurones in deep laminae. These cells displayed a multicomponent peripheral receptive field, comprising an excitatory firing zone, a low-probability firing fringe, and adjacent inhibitory zones. Deep DHNs presented similar intrinsic properties to those observed in vitro, including plateau potentials. These plateaus, underlying high frequency accelerating discharges and after-discharges, were triggered by mechanical stimulation of the excitatory receptive field. Persistent activities induced by activation of plateau potentials were interrupted by stimulation of peripheral inhibitory zones. Moreover, we show that plateau activation is necessary for the expression of windup in response to repetitive, nociceptive stimulation. Finally, using the spinal nerve ligation model of neuropathy, we demonstrate a significant increase in the proportion of plateau neurones in deep dorsal laminae. Our data, therefore, establish that intrinsic amplification properties are expressed within intact spinal circuits and suggest their involvement in neuropathy-induced hyperexcitability of deep DHNs.

Do burn injuries during infancy affect pain and sensory sensitivity in later childhood?

Studies in animals and humans suggest that neonatal and early infant pain or stress experiences can induce long-term alterations in somatosensory and pain processing. We studied pain and sensory sensitivity in school-aged children (9–16 years) who had suffered moderate (N=24) or severe (N=24) burn injuries in infancy (6–24 months of age) and 24 controls. Quantitative sensory testing entailing detection and pain thresholds for thermal and mechanical stimuli and perceptual sensitization to tonic heat and repetitive mechanical stimuli was performed. Two testing sites (thenar, trigeminal region), both not affected by the burn injury, were used to determine whether there are global changes in pain sensitivity. The result pattern suggests a differential impact of burn severity. Compared to controls, moderately burned children showed significantly higher mechanical detection thresholds (thenar) and significantly lower mechanical pain thresholds and significantly greater perceptual sensitization to repetitive mechanical stimuli (both testing sites). No significant alterations were observed for thermal stimuli. In contrast, severely burned children showed, compared to controls, primarily alterations in thermal pain sensitivity (elevated pain thresholds at both testing sites, significantly greater perceptual sensitization at the thenar). In these children, mechanical pain sensitivity and detection thresholds were not consistently altered. This differential pattern of altered sensory and pain sensitivity may reflect differences in experienced stress, pain and analgesic treatment between moderately and severely burned children. Most importantly, our findings suggest that early traumatic and painful injuries, such as burns, can induce global, long-term alterations in sensory and pain processing.

Depression and changed pain perception: Hints for a central disinhibition mechanism

Although patients with a depressive disorder report often of pain, their sensitivity to experimental pain is controversial, probably due to differences in sensory testing methods and to the lack of normal values. Therefore, we used a standardized and validated comprehensive sensory testing paradigm to assess the peripheral and central nervous system performance in depressive patients compared to healthy controls and chronic pain patients with fibromyalgia syndrome (FMS), in which depression is a common comorbidity. Twenty-five depressive psychiatric inpatients (pain-free: n = 20), 35 FMS outpatients and 25 healthy controls underwent quantitative sensory testing (QST), including thermal and mechanical detection and pain thresholds, pain sensitivity and responsiveness to repetitive noxious mechanical stimuli (wind-up). In depressive disorder (to a lesser extent also in FMS), significantly decreased cold pain thresholds and an increased wind-up were found, although the mechanical pain thresholds and pain sensitivity were comparable to those of the healthy controls. All the detection thresholds were within the normal range in all the groups. In depressive disorder, there were no significant side differences in the detection and pain thresholds. The results contradict the former assumption of a general insensitivity to experimental pain in depressive disorder. In the mostly pain-free patients signs of an enhanced central hyperexcitability are even more pronounced than usually found in chronic pain patients (e.g. FMS), indicating common mechanisms in depressive disorder and chronic pain in accordance with the assumption of non-pain associated mechanisms in depressive disorder for central hyperexcitability, e.g. by inhibited serotonergic function. Furthermore, this trial demonstrates the feasibility of QST in depressive patients.

Somatic Pain Sensitivity in Children With Recurrent Abdominal Pain

Evidence is accumulating that recurrent abdominal pain (RAP) in children is associated with visceral hyperalgesia. However, it is not known whether somatic sensitivity is altered as well. Therefore, the aim of our study was to assess somatic pain sensitivity in children with RAP and healthy controls at the abdomen and a distal site (thenar). We examined 20 children with RAP (age 8-14) and 23 healthy control children (age 9-14). Heat and mechanical pain thresholds as well as measures of perceptual sensitization in response to repetitive mechanical or tonic thermal noxious stimulation were assessed. At the abdominal site, pain sensitivity in children with RAP did not differ significantly when compared to controls. At the thenar, pain thresholds of children in the RAP group were not significantly different from control children. However, children with RAP showed less perceptual sensitization in response to tonic heat and repetitive mechanical stimuli (ps <or= 0.05) than controls. We found no evidence for somatic hyperalgesia in RAP arguing against generalized hyperalgesia in these children. Somatic hypoalgesia at the thenar might either be related to a dysregulation of sensory processing and/or attentional avoidance of pain-related stimuli.

Long-term alteration of pain sensitivity in school-aged children with early pain experiences

While animal studies suggest that neonatal pain experiences induce long-term alterations in pain sensitivity, no such data exist in humans. Changes in pain sensitivity in school-aged children (9–14 years) who were born preterm or fullterm, had been hospitalized for a prolonged period of time after birth and had undergone repeated painful procedures while being treated in a Neonatal Intensive Care Unit (NICU) were determined. A retrospective cohort study of 19 preterm (⩽31 weeks gestational age) and 20 fullterm children (⩾37 weeks gestational age) treated at least 3 days in a NICU at a University Hospital and 20 fullterm control children without NICU experience was performed. Perceptual sensitization to tonic heat and repetitive mechanical stimuli as well as heat pain and mechanical pain thresholds were obtained at the thenar and a trigeminal site. Length of hospitalization and NICU treatment was significantly higher in preterm than fullterm children. Nonetheless, both preterm and fullterm children with NICU experience showed greater perceptual sensitization to tonic heat and elevated heat pain thresholds at both sites. Mechanical pain threshold and perceptual sensitization did not differ between groups. Consistent with findings in animals, repeated pain experiences during the neonatal period were associated with alterations in thermal pain responsivity in school-aged preterm and fullterm children that was characterized by enhanced perceptual sensitization to prolonged painful stimulation and hypoalgesia to brief heat pain stimuli. Our findings suggest that repeated pain experiences in neonates may induce activity-induced changes in the functioning of pain pathways that persist well beyond infancy.

Contact heat-evoked temporal summation: Tonic versus repetitive-phasic stimulation

Temporal summation (TS) is usually evoked by repetitive mechanical or electrical stimuli, and less commonly by tonic heat pain. The present study aimed to examine the TS induction by repetitive-phasic versus tonic heat pain stimuli. Using 27 normal volunteers, we compared the extent of summation by three calculation methods: start-to-end pain rating difference, percent change, and double-logarithmic regression of successive ratings along the stimulation. Subjects were tested twice, and the reliability of each of the paradigms was obtained. In addition, personality factors related to pain catastrophizing and anxiety level were also correlated with the psychophysical results. Both paradigms induced significant TS, with similar increases for the repetitive-phasic and the tonic paradigms, as measured on 0–100 numerical pain scale (from 52.9 ± 11.7 to 80.2 ± 15.5, p < 0.001; and from 38.5 ± 13.3 to 75.8 ± 18.3, p < 0.001, respectively). The extent of summation was significantly correlated between the two paradigms, when calculated by absolute change ( r = 0.543, p = 0.004) and by regression ( r = 0.438, p = 0.025). Session-to-session variability was similar for both paradigms, relatively large, yet not biased. As with other psychophysical parameters, this poses some limitations on TS assessment in individual patients over time. The extent of TS induced by both paradigms was found to be associated with anxiety level and pain catastrophizing. Despite some dissimilarity between the repetitive-phasic and the tonic paradigms, the many similarities suggest that the two represent a similar physiological process, even if not precisely the same. Future clinical applications of these tests will determine the clinical relevance of the TS paradigms presented in this study.

Primary hyperalgesia to mechanical and heat stimuli following subcutaneous bee venom injection into the plantar surface of hindpaw in the conscious rat: a comparative study with the formalin test

To elucidate the underlying mechanisms of pathological pain, it is important and necessary to develop an animal model characterized by both spontaneous tonic pain and hyperalgesia with a prolonged duration post-tissue injury. In this report, we investigated whether the two animal models of spontaneous tonic pain (the formalin test and the bee venom test) could develop a hyperalgesia to mechanical and thermal stimuli in the injured area following subcutaneous (s.c.) administration of the two chemical agents into the plantar surface of one hindpaw in the conscious rats. It was found that the persistent nociceptive response (flinching and lifting/licking the injected hindpaw) was monophasic and lasted for 1–2 h followed by a 72–96 h period of reduction in mechanical threshold and heat latency of withdrawal reflex in the bee venom injection area; however, in contrast, the spontaneous pain-related response was biphasic followed by a permanent hypoalgesia or analgesia in the formalin injection area although the duration and response intensity of spontaneous pain was comparable with those following bee venom treatment. Subcutaneous. bee venom injection also produced a distinct reduction of heat latency on the contralateral hindpaw, while s.c. formalin did not. On the other hand, s.c. bee venom injection produced a striking edema and redness of the plantar surface for nearly the same period as the development of hyperalgesia, while the edema and redness could not be obviously observed after the formalin treatment. In the control study, repetitive suprathreshold mechanical or heat stimuli applied to the plantar surface with or without saline treatment did not significantly influence the mechanical threshold or heat latency, suggesting that the phenomena of mechanical and heat hyperalgesia were not the effects of vehicle treatment or those of the stimulus modalities themselves. Taken together, our present results showed that in contrast to s.c. formalin injection, subcutaneous. bee venom injection produced little tissue damage but a striking inflammation accompanied by a prolonged spontaneous pain and a pronounced primary hyperalgesia to mechanical and heat stimuli in the treated hindpaw and a heat, but not mechanical, hyperalgesia in the contralateral hindpaw, implicating that bee venom model may have more advantages over the formalin test and probably other chemoirritants to study the neural mechanisms underlying pathological pain and, especially, the relationship between spontaneous pain and development of hyperalgesia.

Hierarchy of Habituation Induced by Mechanical Stimuli in Caenorhabditis elegans

C. elegans becomes habituated to repetitive mechanical stimuli. We compared the habituated states induced by three types of mechanical stimuli: touch on the head (head-touch), touch on the anterior body (body-touch), and mechanical tapping of the Petri dish, all of which evoke backward movement. The habituation patterns were similar, but differed in retention period and/or the rate of recovery. We found a hierarchy between the habituated states induced by the three types of mechanical stimuli in the decreasing order of head-touch, body-touch, and tap stimulus. Evidence is presented that the hierarchy is brought out by the magnitude of stimuli rather than by independent neural pathways.

The relationship between sensory thresholds and mechanical hyperalgesia in nerve injury

The paradoxical combination of sensory loss within the area where pain is felt together with pain evoked by non-noxious stimuli (allodynia) is a characteristic feature of neuropathic pain. This study examined the relationship between (mechanical and thermal) pain thresholds and dynamic and static hyperalgesia in 15 patients with traumatic nerve injury and brush-evoked pain. Sensory tests were carried out both in the allodynic skin area and in the unaffected contralateral mirror image skin. The sensory characteristics included: visual analogue scale (VAS) score of ongoing pain, detection and pain threshold to thermal and mechanical stimuli, and temporal summation to repetitive heat and pinprick stimuli. Temporal summation was evoked by pinprick stimuli at 2.0 Hz but not at 0.2 Hz in allodynic skin. No difference was observed in temporal summation to heat stimuli. There was a significant and inverse relation between heat and cold pain difference and mechanically evoked pain. Patients with heat hyperalgesia had a significantly higher VAS score of mechanical hyperalgesia than patients with heat hypoalgesia. There was no relationship between dynamic and static evoked hyperalgesia. These findings suggest a differential processing of repetitive thermal and mechanical stimuli in the central nervous system. Both dynamic and static mechanical hyperalgesia are maintained by activity in heat-sensitive nociceptors, but they are probably mediated by distinct mechanisms.