Interaction between local blood flow and tolerance to prolonged pain in the elderly.

PURPOSE: We aimed to explore the link between local vasodilation and pain perception in elderly subjects, testing the hypothesis that altered local cutaneous blood flow participates in the decrease in pain tolerance with age. METHOD: Sixty-eight young and 83 older participants performed a pain tolerance test in which they hold their hand in an airtight box in which air temperature was regulated at 65 °C until the pain became unbearable. Participants continuously estimated pain intensity. Skin temperature and local blood flow in the box-exposed hand were continuously monitored. RESULTS: In the young group, 97% of subjects resisted pain until the end of the test, whereas only 53% in the elderly group managed to do so, indicating that pain tolerance is impaired in the elderly. Among all participants, the skin temperature associated with the first pain sensation was below the threshold for nociceptor activation (43 °C). Interestingly, blood flow in the elderly group was correlated with pain judgment, whereas no such correlation was observed in the young. CONCLUSION: Our results suggest that the local vasodilator response induced by local heating may be involved in pain perception and may influence thermal pain tolerance with aging. These results could contribute to a better understanding of vascular deficits and the development of chronic pain in vascular pathologies.

An electronical stimulator for quantitative sensory testing and evoked potential analysis of tactile Aß nerve fibers.

OBJECTIVE: We aimed to determine the ability of an innovative device, the Cutaneous Mechanical Stimulator (CMS), to evaluate touch sensory pathways in Human. METHODS: Two experiments were conducted in 23 healthy volunteers aged 20-30 years. In the first, mechanical detection thresholds (MDTs) were assessed using Semmes-Weinstein monofilaments and the CMS. In the second experiment, touch-evoked potentials (TEPs) elicited by tactile stimulation of the CMS on the left hand dorsum and left foot dorsum were recorded. Electroencephalographic (EEG) data were recorded at each cutaneous stimulation site in blocks of 20 tactile stimulations delivered by the CMS. The data were segmented into 1000-ms epochs. RESULTS: MDTs measured by monofilaments and by the CMS were equivalent. Analyses of TEPs showed N2 and P2 components. The latencies of the N2 components on the hand dorsum and foot dorsum resulted in an estimated average conduction velocity of about 40 m.s-1, within the range of Aß fibers. CONCLUSIONS: These findings showed that the CMS could assess touch sensory pathways in young adults. SIGNIFICANCE: The CMS can offer new research perspectives, as this device allows easy assessment of the MDT and enables estimation of fiber conduction velocities after tactile stimulation by the device synchronized with EEG recordings.

Preserved distraction analgesia but greater impact of pain on task performance in older adults compared with younger subjects.

OBJECTIVE: In this study, we compared two working memory conditions to study the analgesic effect of a distraction in elderly vs young people and the effect of pain on performance on the distracting task. METHODS: Younger (n=27) and older (n= 34) subjects performed 1- and 2-Back working memory tasks, representing low and high cognitive loads, respectively. Infrequent, brief hot nociceptive and cold non-nociceptive stimulations were delivered 100 ms before visual N-Back stimuli. Contact heat-evoked and cold-evoked potentials (N2P2 component) were analyzed in the absence of cognitive tasks and during the N-Back tasks. We compared the pain and cold intensity ratings and reaction times in trials preceded by nociceptive and cold stimulations and in trials not preceded by thermal stimulations between groups and between N-Back conditions. RESULTS: In both groups, performing the 1- and 2-Back working memory tasks reduced the perceived intensity of nociceptive and cold stimuli. In elderly subjects performing 2-Back memory tasks, response times to trials after nociceptive stimulation were longer than those to trials after cold or non-stimulation. By contrast, thermal stimulations had no effect on reaction times in young subjects. The amplitude of the N2P2 component was lower in the older than in the younger group in the absence of a cognitive task. In the older group, N-Back tasks had no effect on the N2P2 amplitude, whereas they reduced N2P2 amplitude in the young. CONCLUSION: Distraction analgesia is preserved in elderly subjects. However, this successful pain modulation seems to be accompanied by performance costs in the distracting tasks.

Investigating cold Aδ fibers in the 0-40 °C temperature range: A quantitative sensory testing and evoked potentials study.

OBJECTIVE: To evaluate the activity of cold Aδ-type fibers to thermal stimuli above human skin temperature (i.e., >32 °C). METHODS: Twenty young adults aged 20-24 years participated in this study. The cold-detection threshold was measured from a basal temperature of 40 °C using an adaptive staircase method with high-speed cooling ramps (170 °C/s). A total of 150 stimulations at 36 °C, 32 °C, 28 °C, 24 °C, 20 °C, 16 °C, 12 °C, 8 °C, 4 °C and 0 °C (15 each) were performed. After each stimulation, subjects estimated the intensity of cold sensation using a visual analog scale, and evoked potentials were recorded. RESULTS: The average cold-detection threshold was 35 °C (SD = 1.8). Regardless of the stimulation temperature, subjects reported a cooling sensation. Interestingly, reported increments in sensation were prominent for stimulation temperatures between 32 °C and 20 °C, but below this latter temperature sensations varied only very slightly. Evoked potential recordings revealed that decreasing temperature stimuli from a baseline of 40 °C induced a previously unreported N2P2 component with a mean N2 peak latency of 275 ms (SD = 13.1). The peak-to-peak amplitude of the N2P2 complex increased as the intensity of the cooling stimulation increased, exhibiting a profile comparable to subject-perceived intensity, namely, a major increase up to 20 °C, followed by a plateau to 0 °C. CONCLUSIONS: The cool sensations reported by subjects were likely conveyed by Aδ fibers rather than by slow-conducting C fibers. Moreover, our rapid stimulation technique starting from a high temperature (40 °C) was capable of a) generating cold sensations at stimulation temperatures between 36 °C and 32 °C, and b) revealing the optimal activation range of Aδ fibers (20 °C-28 °C). Any decrease in temperature below this range did not result in a significant increase in sensation and thus probably did not evoke a significant increase in Aδ fiber activity. SIGNIFICANCE: The regular assessment of cold sensation in peripheral neuropathies (i.e., with temperatures below 32 °C), could be completed by investigating cold-detection thresholds at temperatures ranging from 40 °C to 32 °C. Indeed, the absolute threshold of cold perception appears to start at 35 °C. Changes in the activation threshold of cold fibers were more easily detectable at this level.

Accurate Determination of the Cold Detection Threshold with High-Speed Cooling of the Skin.

OBJECTIVE: This study used high-speed cooling of the skin and exact control of stimulus duration to measure the cold detection threshold in healthy participants. The objective was to compare the method of limits, in which the temperature is slowly and gradually increased/decreased until the subject perceives the stimulation, and the method of levels, in which the subject must detect brief thermal stimulations close to the threshold of perception. METHODS: Twenty healthy volunteers (nine women, 11 men) aged 20-30 years participated in the study. The method of limits and method of levels were performed in all subjects in a counterbalanced order. Four cold detection thresholds were measured with the method of levels, with a temperature ramp of 300°C/sec and stimulus durations of 50 ms, 100 ms, 300 ms, and 500 ms. Three thresholds were measured with the method of limits, with temperature ramps of 1°C/sec, 2°C/sec, and 4°C/sec. RESULTS: On average, the cold detection thresholds were -0.47°C below skin temperature with the method of levels and -1.67°C the method of limits. Interindividual variability was significantly lower with the method of levels than with the method of limits. CONCLUSIONS: These results suggest that the method of levels is more accurate than the method of limits for measuring cold detection threshold. The improvement of cold detection threshold measurement may provide new perspectives to more precisely assess the function of A-delta fibers and the spino-thalamic pathway.

Involvement of Frontal Functions in Pain Tolerance in Aging: Evidence From Neuropsychological Assessments and Gamma-Band Oscillations.

Reduced pain tolerance may be one of the possible explanations for high prevalence of chronic pain among older people. We hypothesized that age-related alterations in pain tolerance are associated with functioning deterioration of the frontal cortex during normal aging. Twenty-one young and 41 elderly healthy participants underwent a tonic heat pain test, during which cerebral activity was recorded using electroencephalography (EEG). Elderly participants were divided into two subgroups according to their scores on executive tests, high performers (HPs; n = 21) and low performers (LPs; n = 20). Pain measures [exposure times (ETs) and perceived pain ratings] and cerebral activity were compared among the three groups. ETs were significantly lower in elderly LPs than in young participants and elderly HPs. Electroencephalographic analyses showed that gamma-band oscillations (GBOs) were significantly increased in pain state for all subjects, especially in the frontal sites. Source analysis showed that GBO increase in elderly LPs was contributed not only by frontal but also by central, parietal, and occipital regions. These findings suggest that better preservation of frontal functions may result in better pain tolerance by elderly subjects.

Thermal sensitivity in humans at the depth of thermal receptor endings beneath the skin: validation of a heat transfer model of the skin using high-temporal resolution stimuli.

PURPOSE: The bioheat transfer equation predicts temperature distribution in living tissues such as the skin. This study aimed at psychophysically validating this model in humans. METHODS: Three experiments were performed. In the first, participants were asked to judge the thermal intensity of stimuli with combinations of intensity and duration that yielded, according to the model, identical temperatures at the thermoreceptor's depth. In experiment 2, participants' thermal detection thresholds for stimuli of different durations were measured to verify whether these thresholds correspond, according to the model, to equivalent temperatures at the thermoreceptor's location. In experiment 3, an alternative forced choice method was used, in which subjects indicated which of the two consecutive thermal stimulations was more intense. RESULTS: The model predicted results that agreed with subjects' perceptions. Participants judged stimuli of different combinations of intensities and durations yielding identical temperature at the receptor level as having equivalent intensity. Moreover, although cold detection thresholds for stimuli of different durations differed for temperatures of the stimulating probe, stimulations using the model's parameters showed equivalence at the depth of the thermal receptors. Furthermore, stimuli with temperature/duration combinations for which the model predicts temperature equivalence at the depth of the receptors corresponded to subjective equalization. CONCLUSION: These findings indicate that heat transfer models provide good estimates of temperatures at the thermal receptors. Use of these models may facilitate comparisons among studies using different stimulation devices and may facilitate the establishment of standards involving all stimulation parameters.

Effects of thermosensory aging well demonstrated by cold stimulations with high temporal resolution.

INTRODUCTION: The method of limits (MLi) is the most commonly used paradigm to measure the threshold of thermal stimuli. However, the threshold measured by MLi is dependent on reaction time (RT). Because RT in adults increases with age, the inclusion of RT in the MLi paradigm may result in an overestimation of thermal threshold in the older individuals. METHODS: A device with a very rapid cooling rate (300°C/s) was employed to measure cool thresholds by using the method of levels (MLe), a method independent of RT, in 11 older patients and 14 younger adults. RESULTS: Compared with the MLi, the MLe resulted in a greater than 2°C gain in threshold measurement accuracy in older patients. DISCUSSION: The MLe confirmed that cool perception threshold is dependent on age. The use of MLe provides new opportunities for the study of mechanisms underlying age-associated alterations in thermal perception. Muscle Nerve 60: 141-146, 2019.

Modification of Descending Analgesia in Aging: Critical Role of the Prefrontal Cortex.

OBJECTIVE: Aging has been associated with increases in pain threshold and reductions in tolerance threshold, as well as a deficiency in endogenous pain inhibition. Top-down pain modulation mainly involves the frontal cortex network, which is also one of the most vulnerable brain regions in aging. As the frontal cortex also sustains executive functions, we aimed to determine whether reductions in executive functions subtended by the frontal network are associated with the lack of descending inhibitor control in pain-free elderly participants. METHODS: Executive functions were assessed in pain-free elderly participants using neuropsychological tests. Endogenous inhibition of pain was investigated using the paradigm of conditioned pain modulation. We compared pain thresholds before and after the conditioned pain modulation procedure in older and younger participants and in seniors with poor and good performances on executive tests. RESULTS: Younger participants showed a significant inhibitory effect of phasic pain during prolonged pain stimulation. Older participants with good performance on executive tests showed an absence of inhibiting effect, whereas older participants with poor performance showed a facilitating effect, indicating a significant link between cognitive functions and mechanisms of endogenous inhibition of pain. DISCUSSION: These results highlight a significant link between cognitive functions and mechanisms of endogenous inhibition of pain and open new perspectives in investigations of chronic pain in aging.

Observational study found that even small variations in light can wake up very preterm infants in a neonatal intensive care unit.

AIM: This prospective observational study evaluated the behavioural responses of very preterm infants to spontaneous light variations. METHODS: We measured spontaneous light variations in the incubators of 27 very preterm infants, with a median gestational age of 28 weeks (range 26-31 weeks), over 10 hours. All of them had been admitted to the neonatal care unit of the Strasbourg University Hospital, France, between April 2008 and July 2009. Two independent raters examined changes in the infants' behavioural states using video recordings. The percentage of awakenings was recorded when there were light variations and during control periods with no changes. RESULTS: We analysed 275 periods following light variations and 275 control periods. The overall percentage of awakenings was greater during periods following a change in light than during control periods (16.3% vs 11%, p = 0.03). The extent of light protection affected the percentage of awakenings. In mild light protection, there were more awakenings following changes in light than in control periods (25.6% vs 6.7%, p = 0.01). This difference was not found in high light protection. CONCLUSION: Very preterm infants can be woken up by small variations in light, when the light protection in their incubator is insufficient.

Reduced parahippocampal theta activity during spatial navigation in low, but not in high elderly performers.

OBJECTIVE: Cognitive aging varies widely among individuals. Whereas optimal cognitive agers show highly preserved cognitive functions throughout life, other subjects experience cognitive deficits in various cognitive domains. Among them, elderly individuals frequently report difficulties in spatial navigation. In this study, we aimed to determine whether elderly participants with different cognitive profiles would perform differently at a navigation task, and explore underlying medial hippocampal activity. METHOD: Two groups of elderly subjects were selected, high- and low-performing (HP and LP, respectively), based on their performance on a detailed neuropsychological examination. A group of young adults was recruited as controls. Cerebral activity was recorded by electroencephalography (EEG) during a virtual navigation task in which participants had 3 trials to find their way in mazes. We analyzed theta activity during navigation in the mazes and performed source reconstruction analyses. RESULTS: The LP group was less accurate than the HP group during the navigation task. Theta activity during navigation was greater in HP subjects compared with controls, whereas that theta activity was reduced in LP subjects. Moreover, theta activity in the left parahippocampal gyrus increased across trials in HP, but not in LP, subjects. CONCLUSION: Elderly participants performed differently at a navigation task according to their cognitive profile: elderly with cognitive deficits seem to have greater difficulties in spatial navigation than HP elderly. Navigational difficulties in elderly with cognitive deficits might be related to functional alteration of the parahippocampal gyrus. (PsycINFO Database Record

An autonomous, automated and mobile device to concurrently assess several cognitive functions in group-living non-human primates.

Research methods in cognitive neuroscience using non-human primates have undergone notable changes over the last decades. Recently, several research groups have described freely accessible devices equipped with a touchscreen interface. Two characteristics of such systems are of particular interest: some apparatuses include automated identification of subjects, while others are mobile. Here, we designed, tested and validated an experimental system that, for the first time, combine automatization and mobility. Moreover, our system allows autonomous learning and testing of cognitive performance in group-living subjects, including follow-up assessments. The mobile apparatus is designed to be available 24h a day, 7days a week, in a typical confined primate breeding and housing facility. Here we present as proof of concept, the results of two pilot studies. We report that rhesus macaques (Macaca mulatta) learned the tasks rapidly and achieved high-level of stable performance. Approaches of this kind should be developed for future pharmacological and biomedical studies in non-human primates.

Gamma oscillatory activity is impaired in episodic memory encoding with age.

The present study proposes to investigate age-related episodic memory impairment in encoding. We collected ERPs in young and old participants performing a word-encoding task. For subsequently remembered words, young adults had greater activity at the left and anterior electrode sites, whereas old adults had greater posterior activity. Performance correlated positively with central sites in young adults but with left parietal hemisphere activity in old adults. Plus, a large left frontoparietal network increased its activity during the successful encoding for the Beta (13-30 Hz) and Gamma (30-100 Hz) bands in young adults. Old adults had increased activity in the right posterior parietal region for forgotten words in the Gamma band. Using a source localization analysis, we found that age leads to a decrease in Gamma band cerebral activity during encoding of words in the left hemisphere and the bilateral parahippocampal regions. These findings indicate that encoding impairment with age may be associated with dysfunctional Gamma oscillatory activity across a widespread network of left cortical regions.

Decreased theta power at encoding and cognitive mapping deficits in elderly individuals during a spatial memory task.

The purpose of this study was to investigate the role of theta activity in cognitive mapping, and to determine whether age-associated decreased theta power may account for navigational difficulties in elderly individuals. Cerebral activity was recorded using electroencephalograph in young and older individuals performing a spatial memory task that required the creation of cognitive maps. Power spectra were computed in the frontal and parietal regions and correlated with recognition performance. We found that accuracy of cognitive mapping was positively correlated with left frontal theta activity during encoding in young adults but not in older individuals. Compared with young adults, older participants were impaired in the creation of cognitive maps and showed reduced theta and alpha activity at encoding. These results suggest that encoding processes are impaired in older individual, which may explain age-related cognitive mapping deficits.

Age-Related Decline in Cognitive Pain Modulation Induced by Distraction: Evidence From Event-Related Potentials.

Distraction is known to reduce perceived pain but not always efficiently. Overlapping cognitive resources play a role in both pain processing and executive functions. We hypothesized that with aging, the analgesic effects of cognitive modulation induced by distraction would be reduced as a result of functional decline of frontal networks. Twenty-eight elderly and 28 young participants performed a tonic heat pain test with and without distraction (P + D vs P condition), and 2 executive tasks involving the frontal network (1-back [working memory] and go/no-go [response inhibition]), during which event-related potentials were recorded. A significant age-related difference in modulatory effect was observed during the pain-distraction test, with the older group reporting higher pain perception than the younger group during the P + D than during the P condition. Greater brain activity of early processes (P2 component) in both go/no-go and 1-back tasks correlated with less perceived pain during distraction in younger participants. For later processes, more cognitive control and attentional resources (increased N2 and P3 amplitude) needed for working memory processes were associated with greater pain perception in the older group. Inhibition processes were related to conscious distraction estimation in both groups. These findings indicate that cognitive processes subtended by resources in the frontal network, particularly working memory processes, are elicited more in elderly than in younger individuals for pain tolerance when an irrelevant task is performed simultaneously. Perspective: This study suggests that age-related declines in pain modulation are caused by functional degeneration of frontal cerebral networks, which may contribute to a higher prevalence of chronic pain. Analyzing the impact of frontal network function on pain modulation may assist in the development of more effective targeted treatment plans.

Very preterm infants can detect small variations in light levels in incubators.

AIM: This prospective observational study was designed to improve our understanding of the responses of very preterm infants to light level variations in incubators and to evaluate what determined those reactions. METHODS: The physiological responses of 27 very preterm infants were analysed following variations in the light level environments of their incubators over 10 hours. Heart and respiratory rates, systemic oxygen saturation and regional cerebral oxygen saturations were recorded using near-infrared spectroscopy, and the variation of each parameter was analysed. RESULTS: We analysed 332 light level changes. Heart rate increased by 3.8 beats per minute (range -2.6 to 12.6), respiratory rate by six cycles per minute (-1.5 to 26) and regional cerebral oxygen saturation by 1.1% (-0.5% to 3.9%) (p < 0.05 each) when delta lux was over 50. Only respiratory rate decreased significantly, by -8.4 cycles per minute (-28 to -0.4), when delta lux was 50 or lower (p < 0.05). The initial level of illumination altered the very preterm infants' responses, with higher reactivity for higher ambient light levels. CONCLUSION: Very preterm infants reacted to moderate variations in illumination in their incubator, within recommended ranges of light levels, suggesting that they may detect even small light level variations.

Age-related decline in thermal adaptation capacities: an evoked potentials study.

Aging is associated with changes in thermosensitivity and decreases in the functionality of the autonomic thermoregulation. The underlying mechanisms are, however, not fully understood. Elderly subjects may undergo functional changes in the integration process of the thermal sensory system, especially in their thermal adaptation capacities. To verify this hypothesis, we compared thermal evoked responses in younger and older subjects exposed to thermoneutral (27 °C) and warm (30 °C) environments. In the warm environment, the amplitudes of thermal evoked potentials (EPs) were significantly lower in older than in younger subjects, whereas in the thermoneutral environment, the EP amplitudes were similar in both groups. These findings suggest that thermal adaptation capacities are reduced in elderly individuals, due to a dysfunction of C-fibers with aging, particularly expressed by lowered adaptation capacities to temperature variations.

Infants born very preterm react to variations of the acoustic environment in their incubator from a minimum signal-to-noise ratio threshold of 5 to 10 dBA.

INTRODUCTION: Very early preterm infants (VPIs) are exposed to unpredictable noise in neonatal intensive care units. Their ability to perceive moderate acoustic environmental changes has not been fully investigated. RESULTS: Physiological values of the 598 isolated sound peaks (SPs) that were 5-10 and 10-15 dB slow-response A (dBA) above background noise levels and that occurred during infants' sleep varied significantly, indicating that VPIs detect them. Exposure to 10-15 dBA SPs during active sleep significantly increased mean heart rate and decreased mean respiratory rate and mean systemic and cerebral oxygen saturations relative to baseline. DISCUSSION: VPIs are sensitive to changes in their nosocomial acoustic environment, with a minimal signal-to-noise ratio (SNR) threshold of 5-10 dBA. These acoustic changes can alter their well-being. METHODS: In this observational study, we evaluated their differential auditory sensitivity to sound-pressure level (SPL) increments below 70-75 dBA equivalent continuous level in their incubators. Environmental (SPL and audio recording), physiological, cerebral, and behavioral data were prospectively collected over 10 h in 26 VPIs (GA 28 (26-31) wk). SPs emerging from background noise levels were identified and newborns' arousal states at the time of SPs were determined. Changes in parameters were compared over 5-s periods between baseline and the 40 s following the SPs depending on their SNR thresholds above background noise.

On the selective activation of unmyelinated C-fibers using sinusoidal electrical stimulation: an ERP study.

OBJECTIVE: To verify the possibility of selective activation of C-fibers by a 5-Hz transcutaneous electrical stimulus. METHODS: Because Aß-, Aδ- and C-fibers have different conduction velocities, we verified the selective activation of A- and C-fibers on the basis of evoked potential latencies. We tested whether a 5-Hz sinusoidal electric stimulus could selectively activate C-fibers and consequently generate ultra-late N2/P2 components in the 750-1200 ms range. RESULTS: We found that a 5-Hz sine wave stimulus, whether of high or low intensity, elicited N2/P2 complexes only in the late latencies (160-390 ms), suggesting that A-fibers were concomitantly activated along with C-fibers. CONCLUSIONS: These findings are in agreement with those of previous simulation studies suggesting that activation of fibers of diameter less than 2.5 µm (i.e., C-fibers) at the 5-Hz frequency requires accompanying activity from Aß- and Aδ-fibers. SIGNIFICANCE: Transcutaneous electrical stimulation with sine wave currents of different frequencies does not seem to be a reliable method for the selective assessment of somatosensory pathways.