Tonic Heat Research Articles

Data-driven dynamic profiles of tonic heat pain perception in pain-free volunteers are associated with differences in anandamide levels

Our laboratory previously developed a method for assessing experimentally induced pain perception through a 2-min constant heat pain stimulation. However, the traditional analysis relying on group means struggles to interpret the considerable inter-individual variability due to the dynamic nature of the response. Recently, trajectory analysis techniques based on extended mixed models have emerged, providing insights into distinct response profiles. Notably, these methods have never been applied to pain paradigms before. Furthermore, various socio-demographic and neurobiological factors, including endocannabinoids, may account for these inter-individual differences. This study aims to apply the novel analysis to dynamic pain responses and investigate variations in response profiles concerning socio-demographic, psychological, and blood endocannabinoid concentrations. 346 pain-free participants were enrolled in a psychophysical test involving a continuous painful heat stimulation lasting for 2 min at a moderate intensity. Pain perception was continuously recorded using a computerized visual scale. Dynamic pain response analyses were conducted using the innovative extended mixed model approach. In contrast to the traditional group-mean analysis, the extended mixed model revealed three pain response trajectories. Trajectory 1 is characterized by a delay peak pain. Trajectory 2 is equivalent to the classic approach (peak pain follow by a constant and moderate increase of pain perception). Trajectory 3 is characterized by extreme responses (steep peak pain, decrease, and increase of pain perception), Furthermore, age and blood anandamide levels exhibited significant variations among these three trajectories. Using an innovative statistical approach, we found that a large proportion of our sample had a response significantly different from the average expected response. Endocannabinoid system seems to play a role in pain response profile.

Vagal tone, pain sensitivity and exercise-induced hypoalgesia: The effect of physical activity level.

Vagal activity has analgesic effects that are attributed to exercise-induced hypoalgesia (EIH). High vagal tone and low pain sensitivity are reported in individuals who routinely exercise yet, their association is unclear. Furthermore, it is unknown if the heightened vagal tone following high physical activity predicts and intensifies EIH. Fifty-one healthy participants (27 low-moderately physically active; 27 females) underwent a resting-state electrocardiogram followed by heart rate variability analysis. Pain measurements, including pressure (PPT) and heat (HPT) pain thresholds, ratings of tonic heat pain (THP) and conditioned pain modulation (CPM) paradigm, were conducted pre- and post-exercise on a cycle ergometer. The highly active group demonstrated higher vagal tone compared to the low-moderately active (root mean square of successive differences between R-R intervals: 63.96.92 vs. 34.78 ms, p = 0.018; percentage of successive R-R intervals that exceed 50 ms: 24.41 vs. 11.52%, p = 0.012). Based on repeated-measure ANOVA, the highly active group showed higher PPT at pre-exercise, compared to the low-moderately active group (382 kPa vs. 327 kPa; p = 0.007). Post-exercise, both groups demonstrated EIH, increased HPT (p = 0.013) and decreased THP ratings (p < 0.001). Linear regression revealed that only in the low-moderately active group, higher vagal tone was associated with more efficient pre-exercise CPM and a greater reduction in THP ratings post-exercise (p ≤ 0.01). Highly active individuals demonstrate greater vagal tone and lower pain sensitivity but no greater EIH. Vagal tone moderates pain inhibition efficiency and EIH only in low-moderately active individuals. These findings suggest that physical activity level moderates the vagal-pain association via the endogenous analgesia system. Highly physically active individuals exhibit greater vagal tone and reduced sensitivity to experimental pain, yet they do not benefit more from exercise-induced hypoalgesia (EIH) compared to low-moderately active individuals. Moreover, low-moderately active individuals with greater vagal tone exhibited more efficient endogenous pain inhibition and greater EIH, suggestive of the moderation effect of physical activity level on vagal-pain associations.

The autonomic and nociceptive response to acute experimental stress is impaired in people with knee osteoarthritis: A preliminary study

ObjectiveAlterations in autonomic function are evident in some chronic pain conditions but have not been thoroughly examined in people with osteoarthritis (OA). The study aimed to examine resting autonomic nervous system (ANS) function in people with knee OA, and the response of the autonomic and nociceptive systems to acute stress. MethodsA preliminary cross-sectional study was undertaken involving people with knee OA (n = 14), fibromyalgia (n = 13), and pain-free controls (n = 15). The sympathetic and parasympathetic components of the ANS were assessed through measures of pre-ejection period (PEP), skin conductance level (SCL), and high frequency heart rate variability (HF HRV). The nociceptive system was assessed through pain ratings associated with a tonic heat pain stimulus. In separate sessions, ANS and heat pain measures were assessed at rest and in response to nociceptive and mental arithmetic stressors. ResultsThe knee OA group showed reduced HF HRV at rest and reduced modulation in response to stress. Resting PEP and SCL were normal in the knee OA group but PEP modulation was impaired in both chronic pain groups during nociceptive stress. The expected reduction in tonic heat pain ratings in response to stress was lacking in the knee OA and FM groups. ConclusionPreliminary evidence shows impaired parasympathetic nervous system function at rest and in response to nociceptive and mental stress in people with knee OA, with some evidence of altered sympathetic nervous system function. Impaired ANS function could contribute to ongoing pain experienced, and interventions that target ANS function could be beneficial.

Brain mechanisms associated with facial encoding of affective states.

Affective states are typically accompanied by facial expressions, but these behavioral manifestations are highly variable. Even highly arousing and negative valent experiences, such as pain, show great instability in facial affect encoding. The present study investigated which neural mechanisms are associated with variations in facial affect encoding by focusing on facial encoding of sustained pain experiences. Facial expressions, pain ratings, and brain activity (BOLD-fMRI) during tonic heat pain were recorded in 27 healthy participants. We analyzed facial expressions by using the Facial Action Coding System (FACS) and examined brain activations during epochs of painful stimulation that were accompanied by facial expressions of pain. Epochs of facial expressions of pain were coupled with activity increase in motor areas (M1, premotor and SMA) as well as in areas involved in nociceptive processing, including primary and secondary somatosensory cortex, posterior and anterior insula, and the anterior part of the mid-cingulate cortex. In contrast, prefrontal structures (ventrolateral and medial prefrontal) were less activated during incidences of facial expressions, consistent with a role in down-regulating facial displays. These results indicate that incidences of facial encoding of pain reflect activity within nociceptive pathways interacting or possibly competing with prefrontal inhibitory systems that gate the level of expressiveness.

Aerobic Upper-Limb Exercise-Induced Hypoalgesia: Does It Work?

Background: Aerobic exercise reduces pain sensitivity, a phenomenon known as exercise-induced hypoalgesia (EIH); however, little is known about EIH when the upper limbs are aerobically exercised. This study aimed to test the acute effect of a single aerobic upper-limb exercise on pain threshold and pain intensity in healthy participants, with two different protocols for controlling intensity. Methods: 31 participants performed two 20 min exercise sessions a week apart. In each session, the intensity was controlled by a target heart rate (THR) of 60% of heart rate reserve or by a rate of perceived exertion (RPE) of 7/10 on the Borg scale. Pain threshold for pressure (PPT) heat (HPT) and pain intensity in response to Tonic Heat Pain (THP) were measured pre- and post-exercise. To examine the effect of exercise in each protocol on pain sensitivity, rmANOVA was conducted. Results: Pain sensitivity remained unchanged following arm exercise in both protocols (PPT, p = 0.67; HPT, p = 0.56; and THP p = 0.39). Higher HR in the THR protocol was demonstrated with a significant protocol X time, interaction effect (F(3) = 11.194 p &lt; 0.004). Conclusions: Moderate–high-intensity upper-limb aerobic exercise did not affect pain sensitivity in healthy individuals. Exercise intensity when controlled by THR showed a higher mean heart rate compared to exercise intensity based on RPE.

Electroencephalographic characteristics of children and adolescents with chronic musculoskeletal pain.

The pathophysiology of pediatric musculoskeletal (MSK) pain is unclear, contributing to persistent challenges to its management. This study hypothesizes that children and adolescents with chronic MSK pain (CPs) will show differences in electroencephalography (EEG) features at rest and during thermal pain modalities when compared with age-matched controls. One hundred forty-two CP patients and 45 age-matched healthy controls (HCs) underwent a standardized thermal tonic heat and cold stimulations, while a 21-electrode headset collected EEG data. Cohorts were compared with respect to their EEG features of spectral power, peak frequency, permutation entropy, weight phase-lag index, directed phase-lag index, and node degree at 4 frequency bands, namely, delta (1-4 Hz), theta (4-8 Hz), alpha (8-13 Hz), and beta (13-30 Hz), at rest and during the thermal conditions. At rest, CPs showed increased global delta (P = 0.0493) and beta (P = 0.0002) power in comparison with HCs. These findings provide further impetus for the investigation and prevention of long-lasting developmental sequalae of early life chronic pain processes. Although no cohort differences in pain intensity scores were found during the thermal pain modalities, CPs and HCs showed significant difference in changes in EEG spectral power, peak frequency, permutation entropy, and network functional connectivity at specific frequency bands (P < 0.05) during the tonic heat and cold stimulations. This suggests that EEG can characterize subtle differences in heat and cold pain sensitivity in CPs. The complementation of EEG and evoked pain in the clinical assessment of pediatric chronic MSK pain can better detect underlying pain mechanisms and changes in pain sensitivity.

Are changes in nociceptive withdrawal reflex magnitude a viable central sensitization proxy? Implications of a replication attempt

ObjectiveThe nociceptive withdrawal reflex (NWR) has been proposed to read-out central sensitization (CS). Replicating a published study, it was assessed if the NWR magnitude reflects sensitization by painful heat. Additionally, NWR response rates were compared for two stimulation, the sural nerve at the lateral malleolus (SU) and the medial plantar nerve on the foot sole (MP), and three recording sites, biceps femoris (BF), rectus femoris (RF), and tibialis anterior (TA) muscles. Methods16 subjects underwent one experiment with six blocks of eight transcutaneous electrical stimulations to elicit the NWR while surface electromyography was collected. Tonic heat was concurrently applied in the same dermatome. Temperatures rose from 32 °C in the first to 46 °C in the last block following the previously published protocol. ResultsTonic heat did not influence NWR magnitude. The highest NWR response rate was obtained for MP–TA combination (79%). Regarding elicitation in all three muscles, SU stimulation outperformed MP (59% vs 57%). ConclusionsThe replication failed. NWR magnitude as a CS proxy in healthy subjects needs continued investigation. With respect to response rates, MP–TA proved efficient, whereas SU stimulation seemed preferable for multiple muscle recordings. SignificanceUnclear methodological descriptions in the original study affected CS and NWR replication. The NWR magnitude changes induced by CS may closely depend on the different stimulation methods used.

PC026 / #642 EFFICACY OF ANODAL SUBOCCIPITAL DIRECT CURRENT STIMULATION FOR ENDOGENOUS PAIN MODULATION AND TONIC THERMAL PAIN CONTROL IN HEALTHY PARTICIPANTS: A RANDOMIZED CONTROLLED CLINICAL TRIAL: TRACK 3: RESTORATIVE THERAPIES / NONINVASIVE STIMULATION / NEUROSTIMULATION FOR HEAD AND FACE PAIN

Suboccipital nerve stimulation activates the dorsal rostral pons and anterior cingulate cortex [1, 2], centers that are implicated in mediating endogenous pain modulation (EPM) [3, 4]. Indeed, direct current stimulation (DCS)-mediated pain modulation following suboccipital nerve stimulation in people with chronic pain [5, 6] suggests that the effect of noninvasive DCS applied at the suboccipital (SO) level may indirectly influence EPM. The aim of this study was to evaluate whether a single-session of anodal SO-DCS could potentiate EPM measured as conditioned pain modulation of tonic heat pain intensity in healthy participants, and to compare this effect with observations induced with M1 cortical direct current stimulation [7].

Indicators of central sensitization in chronic neuropathic pain after spinal cord injury.

Central sensitization is considered a key mechanism underlying neuropathic pain (NP) after spinal cord injury (SCI). Two novel proxies for central sensitization were investigated in thoracic SCI subjects with (SCI-NP) and without NP (SCI-nonNP) compared to healthy controls (HC). Specifically, temporal summation of pain (TSP) was investigated by examining pain ratings during a 2-min tonic heat application to the volar forearm. Additionally, palmar heat-induced sympathetic skin responses (SSR) were recorded in order to reveal changes in pain-autonomic interaction above the lesion level. Pain extent was assessed as the percentage of the body area and the number of body regions being affected by NP. Enhanced TSP was observed in SCI-NP (+66%) compared to SCI-nonNP (-75%, p= 0.009) and HC (-59%, p= 0.021). In contrast, no group differences were found (p= 0.685) for SSR habituation. However, pain extent in SCI-NP was positively correlated with deficient SSR habituation (body area: r= 0.561, p= 0.024; body regions: r= 0.564, p= 0.023). These results support the value of TSP and heat-induced SSRs as proxies for central sensitization in widespread neuropathic pain syndromes after SCI. Measures of pain-autonomic interaction emerged as a promising tool for the objective investigation of sensitized neuronal states in chronic pain conditions. We present two surrogate readouts for central sensitization in neuropathic pain following SCI. On the one hand, temporal summation of tonic heat pain is enhanced in subjects with neuropathic pain. On the other hand, pain-autonomic interaction reveals potential advanced measures in chronic pain, as subjects with a high extent of neuropathic pain showed diminished habituation of pain-induced sympathetic measures. A possible implication for clinical practice is constituted by an improved assessment of neuronal hyperexcitability potentially enabling mechanism-based treatment.

Indifference or hypersensitivity? Solving the riddle of the pain profile in individuals with autism.

Excitatory-inhibitory (E/I) imbalance is a mechanism that underlies autism spectrum disorder, but it is not systematically tested for pain processing. We hypothesized that the pain modulation profile (PMP) in autistic individuals is characterized by less efficient inhibitory processes together with a facilitative state, indicative of a pronociceptive PMP. Fifty-two adults diagnosed with autism and 52 healthy subjects, age matched and sex matched, underwent quantitative sensory testing to assess the function of the (1) pain facilitatory responses to phasic, repetitive, and tonic heat pain stimuli and (2) pain inhibitory processes of habituation and conditioned pain modulation. Anxiety, pain catastrophizing, sensory, and pain sensitivity were self-reported. The autistic group reported significantly higher pain ratings of suprathreshold single ( P = 0.001), repetitive (46°C- P = 0.018; 49°C- P = 0.003; 52°C- P < 0.001), and tonic ( P = 0.013) heat stimuli that were cross correlated ( r = 0.48-0.83; P < 0.001) and associated with sensitivity to daily life pain situations ( r = 0.39-0.45; P < 0.005) but not with psychological distress levels. Hypersensitivity to experimental pain was attributed to greater autism severity and sensory hypersensitivity to daily stimuli. Subjects with autism efficiently inhibited phasic but not tonic heat stimuli during conditioned pain modulation. In conclusion, in line with the E/I imbalance mechanism, autism is associated with a pronociceptive PMP expressed by hypersensitivity to daily stimuli and experimental pain and less-efficient inhibition of tonic pain. The latter is an experimental pain model resembling clinical pain. These results challenge the widely held belief that individuals with autism are indifferent to pain and should raise caregivers' awareness of pain sensitivity in autism.

Temporal Summation in Fibromyalgia Patients: Comparing Phasic and Tonic Paradigms.

IntroductionFibromyalgia (FM) is associated with dysfunctional pain modulation mechanisms, including central sensitization. Experimental pain measurements, such as temporal summation (TS), could serve as markers of central sensitization and have been previously studied in these patients, with conflicting results. Our objective in this study was to explore the relationships between two different protocols of TS (phasic and tonic) and test the associations between these measures and other clinical variables.Materials and MethodsIn this cross-sectional analysis of a randomized clinical trial, patients were instructed to determine their pain-60 test temperature, then received one train of 15 repetitive heat stimuli and rated their pain after the 1st and 15th stimuli: TSPS-phasic was calculated as the difference between those. We also administered a tonic heat test stimulus at the same temperature continuously for 30 s and asked them to rate their pain levels after 10 s and 30 s, calculating TSPS-tonic as the difference between them. We also collected baseline demographic data and behavioral questionnaires assessing pain, depression, fatigue, anxiety, sleepiness, and quality of life. We performed univariable analyses of the relationship between TSPS-phasic and TSPS-tonic, and between each of those measures and the demographic and clinical variables collected at baseline. We then built multivariable linear regression models to find predictors for TSPS-phasic and TSPS-tonic, while including potential confounders and avoiding collinearity.ResultsFifty-two FM patients were analyzed. 28.85% developed summation during the TSPS-phasic protocol while 21.15% developed summation during the TSPS-tonic protocol. There were no variables associated TSPS phasic or tonic in the univariable analyses and both measures were not correlated. On the multivariate model for the TSPS-phasic protocol, we found a weak association with pain variables. BPI-pain subscale was associated with more temporal summation in the phasic protocol (ß = 0.38, p = 0.029), while VAS for pain was associated with less summation in the TSPS-tonic protocol (ß = −0.5, p = 0.009).ConclusionOur results suggest that, using heat stimuli with pain-60 temperatures, a TSPS-phasic protocol and a TSPS-tonic protocol are not correlated and could index different neural responses in FM subjects. Further studies with larger sample sizes would be needed to elucidate whether such responses could help differentiating subjects with FM into specific phenotypes.

Adaptation to tonic heat in healthy subjects and patients with sensory polyneuropathy.

Background Adaptation to a constant sensory stimulus involves many sites along the path of sensory volleys towards perception. The evaluation of such phenomenon may be of clinical interest. We studied adaptation to a constant temperature stimulus in healthy subjects to set normative data and in patients with sensory polyneuropathy (SPN), as proof of concept. Methods Twenty-six healthy subjects and 26 patients with SPN in the context of chemotherapy treatment with oxaliplatin for colon cancer were instructed to express through an electronic VAS system (eVAS); the level of sensation felt when a thermode set at either 39º, 41º, 43º, 45º or 47º was applied to their ventral forearm. Results The eVAS recordings showed typically an abrupt onset that slowed to approach maximum sensation and continued with a slow decrease indicating adaptation. The time to respond (TR), the velocity of the initial response (VR), the maximum sensation (MA), the time to reach MA (MAt), the onset of adaptation (AO) and the decrease in the sensation level with respect to MA at 30s after stimulus application (SL30), were dependent on the temperature level in all subjects. However, patients showed significantly delayed TR, slowed VR, decreased MA, delayed AO and reduced SL30, with respect to healthy subjects. Differences were more pronounced at low-temperature levels, with absent AO in 25 patients versus 2healthy subjects at temperatures of 39º and 41ºC. Conclusion The study of adaptation to a constant temperature stimulus can furnish valuable data for the assessment of patients with SPN. SIGNIFICANCE: We studied perceptual changes in the intensity of thermoalgesic sensation during 30s of constant temperature stimulation after an abrupt initial contact in healthy subjects and patients with sensory polyneuropathy. Patients showed delayed time to respond, decreased maximal sensation and reduced adaptation with respect to healthy subjects. Differences were more pronounced at low and intermediate temperatures (39ºC to 43ºC). The method is of easy implementation and shows clinically relevant abnormalities in patients with sensory polyneuropathy.

Intrinsic network activity reflects the fluctuating experience of tonic pain.

Although we know sensation is continuous, research on long-lasting and continuously changing stimuli is scarce and the dynamic nature of ongoing cortical processing is largely neglected. In a longitudinal study, 38 participants across four sessions were asked to continuously rate the intensity of an applied tonic heat pain for 20min. Using group-independent component analysis and dual regression, we extracted the subjects' time courses of intrinsic network activity. The relationship between the dynamic fluctuation of network activity with the varying time courses of three pain processing entities was computed: pain intensity, the direction of pain intensity changes, and temperature. We were able to dissociate the spatio-temporal patterns of objective (temperature) and subjective (pain intensity/changes of pain intensity) aspects of pain processing in the human brain. We found two somatosensory networks with distinct functions: one network that encodes the small fluctuations in temperature and consists mainly of bilateral primary somatosensory cortex (SI), and a second right-lateralized network that encodes the intensity of the subjective experience of pain consisting of SI, secondary somatosensory cortex, the posterior cingulate cortex, and the thalamus. We revealed the somatosensory dynamics that build up toward a current subjective percept of pain. The timing suggests a cascade of subsequent processing steps toward the current pain percept.

The Influence of Examiner Gender on Responses to Tonic Heat Pain Assessments: A Preliminary Investigation.

Background: The influence of examiner gender on pain reporting has been previously explored in both research and clinical settings. However, previous investigations have been limited, with the majority of studies employing single, static assessments of pain (e.g., cold pressor test, verbal pain ratings). The impact of examiner gender on both static and dynamic heat-based pain assessments is currently unknown.Methods: Thirty eight participants (20 females aged 24.1 ± 4.44, and 18 males, aged 24.8 ± 4.54) completed two identical testing sessions, randomized to a male and female examiner in a cross-over design. Pain sensitivity was examined using heat pain thresholds, verbal pain ratings to tonic heat, computerized visual analog scale (CoVAS) rating to tonic heat, and participant-controlled temperature (PCT) heat pain assessments.Results: Female participants reported higher verbal pain to tonic heat with a female examiner compared to male participants, with similar trends for CoVAS responses to tonic heat. Conversely heat pain thresholds and PCT were not significantly influenced by experimenter gender.Conclusions: Overall, verbal ratings were the most impacted by examiner gender, with temperature-based methods such as PCT and pain thresholds showing little to no examiner gender effects. While the gender of the examiner may be an important consideration in the measurement of sex and gender differences in pain research, the choice of pain assessment method may be of similar consequence.

Modulating Brain Rhythms of Pain Using Transcranial Alternating Current Stimulation (tACS) - A Sham-Controlled Study in Healthy Human Participants

Chronic pain is a major health care problem. A better mechanistic understanding and new treatment approaches are urgently needed. In the brain, pain has been associated with neural oscillations at alpha and gamma frequencies, which can be targeted using transcranial alternating current stimulation (tACS). Thus, we investigated the potential of tACS to modulate pain and pain-related autonomic activity in an experimental model of chronic pain in 29 healthy participants. In 6 recording sessions, participants completed a tonic heat pain paradigm and simultaneously received tACS over prefrontal or somatosensory cortices at alpha or gamma frequencies or sham tACS. Concurrently, pain ratings and autonomic responses were collected. Using the present setup, tACS did not modulate pain or autonomic responses. Bayesian statistics confirmed a lack of tACS effects in most conditions. The only exception was alpha tACS over somatosensory cortex where evidence was inconclusive. Taken together, we did not find significant tACS effects on tonic experimental pain in healthy humans. Based on our present and previous findings, further studies might apply refined stimulation protocols targeting somatosensory alpha oscillations. Trial registrationThe study protocol was pre-registered at ClinicalTrials.gov (NCT03805854). PerspectiveModulating brain oscillations is a promising approach for the treatment of pain. We therefore applied transcranial alternating current stimulation (tACS) to modulate experimental pain in healthy participants. However, tACS did not modulate pain, autonomic responses, or EEG oscillations. These findings help to shape future tACS studies for the treatment of pain.

Efficacy of Anodal Suboccipital Direct Current Stimulation for Endogenous Pain Modulation and Tonic Thermal Pain Control in Healthy Participants: A Randomized Controlled Clinical Trial.

The aim of this study was to assess whether anodal DCS applied to the suboccipital (SO) target area could potentiate antinociception assessed primarily with conditioned pain modulation of tonic thermal test stimuli. Randomized double-blinded control trial. Rehabilitation hospital. Healthy participants. Forty healthy participants were randomized to receive either SO-DCS or M1-DCS. The 20-minute 1.5 mA anodal or sham DCS intervention were applied to each participant in randomized order during two test sessions. The primary outcome measure included heterotopic cold-pressor conditioned pain modulation (CPM) of tonic heat pain. Secondary measures included pressure pain threshold and tonic thermal pain intensity. Heterotopic CPM of tonic heat pain intensity was unaffected by either SO-DCS or active M1, including the secondary measures of pressure pain threshold and tonic thermal pain intensity. Although low-power non-significant interactions were identified for DCS intervention (active versus sham) and time (before and after), a significant within-group inhibition of tonic cold pain was identified following SO-DCS (P = .011, mean [SD]: -0.76 ± 0.88 points) and M1-DCS (P < .002: -0.84 ± 0.82 points), without a significant change following sham DCS. Although heterotopic CPM was not facilitated with either SO-DCS or M1-DCS, a general significant inhibition of tonic cold pain intensity was demonstrated following both interventions. The general effects of active DCS compared to sham on tonic cold pain-irrespective of the M1 or SO target-need to be confirmed using standard quantitative sensory testing.

Conditioned Pain Modulation Decreases Over Time in Patients With Neuropathic Pain Following a Spinal Cord Injury

Background Neuropathic pain is a major problem following spinal cord injury (SCI). Central mechanisms involved in the modulation of nociceptive signals have been shown to be altered at the chronic stage, and it has been hypothesized that they might play a role in the development of chronic pain. Objective This prospective longitudinal study aimed to describe the evolution of pain modulation mechanisms over time after SCI, and to explore the relationships with the presence of clinical (neuropathic and musculoskeletal) pain. Methods Patients with an SCI were assessed on admission (n = 35; average of 38 days postinjury) and discharge (n = 25; average of 131 days postinjury) using the International Spinal Cord Injury Pain Basic Data Set. Conditioned pain modulation was assessed using the cold pressor test (10 °C; 120 s) as the conditioning stimulus and tonic heat pain, applied above the level of injury, as the test stimulus (120 s). Heat pain threshold was also assessed. Results A marked decrease in the efficacy of conditioned pain modulation was observed over time, with 30.2% of inhibition at admission and only 12.9% at discharge on average (P = .010). This decrease was observed only in patients already suffering from neuropathic pain at admission and was not explained by a general increase in sensitivity to thermal nociceptive stimuli. Conclusion These results suggest that the presence of neuropathic pain leads to a decrease in conditioned pain modulation over time, rather than supporting the hypothesis that inefficient conditioned pain modulation mechanisms are leading to the development of neuropathic pain.

Decreased Initial Peak Pain Sensation with Aging: A Psychophysical Study.

Background and PurposeAging is associated with an impairment of diverse physiological functions, including nociception. For example, older adults in comparison to young adults, show an overall increase in pain thresholds, reflecting a decline in pain sensitivity and changes in the nociceptive pathways. These results are, however, debated as they were not always replicated depending on the stimulus modality, duration, and location. The aim of the current study was to determine how the temporal evolution of pain intensity during a continuous tonic heat pain test is influenced by aging. More specifically, we wanted to 1) assess the effect of age on initial peak and late-phase pain and 2) determine whether potential age effects depend on the stimulation site.Participants and Methods13 young adults (average of 27.9 years old) and 13 older adults (average of 67.5 years old) participated in this study. Experimental heat pain was evoked on an appendicular (forearm) and axial (lower-back) body region, using a thermode (2-minute stimulation at a constant, individually-adjusted temperature). During the nociceptive stimulation, participants used a computerized visual analogue scale to continuously rate their pain.ResultsWe show that initial peak (0–30 seconds) pain sensation was significantly lower in older adults compared to young adults, while late-phase (30–120 seconds) pain sensation was similar across the two age groups. These results hold true for both stimulation sites, suggesting the existence of an age effect on both appendicular and axial body regions.ConclusionThe lower magnitude of initial peak pain observed in older adults, which affects both appendicular and axial body regions, could reflect generalized peripheral or central alterations of the nociceptive system in older adults. These alterations in older adults could have significant clinical impacts, such as an increased vulnerability to injury or an underestimation of the severity of their pain condition.

Individual differences in pain sensitivity in drug-naive patients with major depressive disorder: an fMRI study.

Patients with major depressive disorder (MDD) often report pain; however, the pain-related brain mechanism that contributes to MDD with pain remains largely unclear. In the current study, we aimed to observe the cortical responses by employing fMRI technique combined with thermal stimulation paradigm in 17 major depressive disorder patients with pain (MDDP), 19 major depressive disorder patients without pain (MDDNP), and 25 age- and gender-matched healthy control (HC) subjects. Participants completed the Hamilton Depression Rating Scale-17 (HAMD-17) and provided pain intensity ratings in response to noxious heat (51°C) during task-fMRI scanning by visual analogue scale (VAS). In our results, there was no difference in pain intensity ratings during tonic heat stimulation between the HC group and MDDNP group (p > 0.05), while the MDDNP group had significantly higher HAMD scores compared with the HC group (p <0.001). The MDDNP group had decreased brain activation in the postcentral gyrus (PCG) compared with the HC group, implying abnormal activation of the PCG may associate with the characterized depressive mood of painless MDD (p < 0.05). Additionally, there was no difference in HAMD scores between the MDDP group and MDDNP group (p > 0.05), while the MDDP group had significantly greater pain during tonic heat stimulation compared with the MDDNP group (p <0.01). The MDDP group showed enhanced activation in the PCG compared with theMDDNP group (p < 0.05), which may relate to the abnormal regulation of pain in painful MDD. Our results suggested that higher PCG activation may play an important role in facilitating the occurrence of pain in depression.

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.