Painful Thermal Stimuli Research Articles

Patients with Impaired Descending Nociceptive Inhibitory System Present Altered Cardiac Vagal Control at Rest

Background: Patients with chronic musculoskeletal pain have a higher chance of presenting impairment in cardiovascular autonomic modulation, which may have implications for cardiovascular events. The autonomic nervous system plays an important role in pain modulation. However, it is unclear whether patients with inefficient descending nociceptive inhibition have poorer cardiovascular autonomic modulation. Objective: To compare the cardiovascular autonomic modulation of patients with musculoskeletal pain who had normal versus impaired functioning of descending nociceptive inhibitory system (DNIS). Study Design: A cross-sectional study. Setting: Physiotherapy outpatient service. Methods: Fifty-six patients with musculoskeletal pain were included. Conditioned pain modulation was assessed by the difference of algometric values held in the dorsal forearm and tibialis anterior muscle, before and after a thermal pain stimulus was employed via the cold pressure test (CPT). Patients with inefficient DNIS in both sites were classified as impaired responders (n = 14). The others were classified as normal responders (n = 42). Cardiac autonomic modulation was monitored at rest by heart rate variability (HRV). The blood pressure response to the CPT was used as a proxy of sympathetic responsiveness. Results: Most of the patients were women (60%) and had chronic pain (75%). The groups had similar demographic characteristics. Patients with impaired DNIS showed lower HRV [RMSSD (P = 0.020), SDRR (P = 0.009), HF (ms2 ) (P = 0.027), LF (ms2 ) (P = 0.004), and total power (P = 0.002)]. The blood pressure response to CPT was similar between groups (systolic pressure, P = 0.813; diastolic pressure, P = 0.709). Limitation: Physical activity level, emotional changes, and visceral pathologies can alter the autonomic nervous system and may represent potential confounders. The low number of patients may have biased the results. Conclusion: Patients with impaired DNIS presented lower resting HRV, indicating an altered vagal control of the heart. In contrast, the blood pressure response to a sympathoexcitatory stimulus was preserved. The study was approved by the Research Ethics Committee of Augusto Motta University Centre (CAAE number: 46245215.9.0000.5235), and all patients signed the Informed Consent Form. Key words: Musculoskeletal pain, autonomic nervous system, heart rate, chronic pain, diffuse noxious inhibitory control, blood pressure, sympathetic nervous system, parasympathetic nervous system

Acute pain intensity monitoring with the classification of multiple physiological parameters

Current acute pain intensity assessment tools are mainly based on self-reporting by patients, which is impractical for non-communicative, sedated or critically ill patients. In previous studies, various physiological signals have been observed qualitatively as a potential pain intensity index. On the basis of that, this study aims at developing a continuous pain monitoring method with the classification of multiple physiological parameters. Heart rate (HR), breath rate (BR), galvanic skin response (GSR) and facial surface electromyogram were collected from 30 healthy volunteers under thermal and electrical pain stimuli. The collected samples were labelled as no pain, mild pain or moderate/severe pain based on a self-reported visual analogue scale. The patterns of these three classes were first observed from the distribution of the 13 processed physiological parameters. Then, artificial neural network classifiers were trained, validated and tested with the physiological parameters. The average classification accuracy was 70.6%. The same method was applied to the medians of each class in each test and accuracy was improved to 83.3%. With facial electromyogram, the adaptivity of this method to a new subject was improved as the recognition accuracy of moderate/severe pain in leave-one-subject-out cross-validation was promoted from 74.9 ± 21.0 to 76.3 ± 18.1%. Among healthy volunteers, GSR, HR and BR were better correlated to pain intensity variations than facial muscle activities. The classification of multiple accessible physiological parameters can potentially provide a way to differentiate among no, mild and moderate/severe acute experimental pain.

Lysozyme over‐expression during nerve injury excites Aδ & C fibres in a fibre specific manner to incite neuropathic pain

Human lysozyme is one of the most extensively studied proteins yet its exact physiological functions still remain a mystery. Here, we highlight a hitherto unrecognized role of lysozyme in neuropathic pain and neuronal excitability. Injection of lysozyme alone in healthy rats leads to heightened sensitivity in them towards both mechanical and thermal pain stimuli. Also, in rat models of neuropathic pain, lysozyme is over – expressed and its down – regulation by siRNA or inhibition of its activity by its disaccharide inhibitor ‐ chitobiose relieves pain confirming a causal role of lysozyme in neuropathic pain. Moreover, as the catalytically incompetent lysozyme or its chemically inhibited counterparts fail to provoke pain indicate that it deploys its catalytic site for eliciting pain. Bath application of lysozyme remarkably increased both the spontaneous excitatory potentials and currents (sEPSPs & sEPSCs) and the amplitudes of afferent mediated evoked excitatory synaptic inputs (eFPSPs & eEPSCs) in Aδ fibres in a fibre specific manner in the dorsal horn neurons. It also increased paired pulsed ratio only in the C‐fibres. When complexed with chitobiose it does not lead to any change in neuronal excitability. Thus, lysozyme excites neurons by deploying its catalytic region in a fibre specific manner. Further, we show that it deploys its catalytic site to recruit Annexin A2 to transduce TLR4→NFkβ signaling pathway which may culminate in the fusion of neurotransmitter vesicles at the synapse to manifest neuronal excitability and eventually pain. Thus, glycan inhibitors of lysozyme and antagonists of the pathway recruited by it to inflict pain pave not only the way for novel approaches for dissecting the molecular mechanism of neuropathic pain but also for treating this unmet medical need efficaciously.Support or Funding InformationCouncil of Scientific and Industrial Research, India to ASThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

The good, the bad, and the suffering. Transient emotional episodes modulate the neural circuits of pain and empathy

People's sensitivity to first-hand pain is affected by their ongoing emotions, with positive states (joy, amusement) exerting analgesic-like effects, and negative states (sadness, fear) often enhancing the subjective experience. It is however less clear how empathetic responses to others’ pain are affected by one's own emotional state. Following embodied accounts that posit a shared representational code between self and others’ states, it is plausible that pain empathy might be influenced by emotions in the same way as first-hand pain. Alternatively, other theories in psychology suggest that social resources (including empathetic reactions) might be enhanced by positive states, but inhibited by negative states, as only in the former case, one's mindset is sufficiently broad to take into consideration others’ needs. To disambiguate between these opposing predictions, we conducted two experiments in which volunteers observed positive, neutral, or negative video clips, and subsequently either received painful thermal stimuli on their own body (first-hand pain), or observed images of wounded hands (others’ pain). We measured subjective pain ratings as well as physiological responses and brain activity using fMRI. We found that, contrary to the case of first-hand pain, others’ pain produced weaker galvanic responses and lower neural activity in anterior insula and middle cingulate cortex following negative (relative to neutral and positive) videos. Such inhibition was partially counteracted by personal empathy traits, as individuals with higher scores retained greater sensitivity to others’ pain after negative emotion induction, in both behavioral and neural responses in medial prefrontal cortex. Furthermore, multivoxel pattern analysis confirmed similar neural representation for first-hand and others’ pain in anterior insula, with representation similarity increasing the more the video preceding the observation of others’ suffering was positive. These findings speak against the idea that emotion induction affects first-hand and others’ pain in an isomorphic way, but rather supports the idea that contrary to negative emotions, positive emotions favors a broader access to social resources.

Sex Differences in the Psychophysical Response to Contact Heat in Moderate Cognitive Impairment Alzheimer's Disease: A Cross-Sectional Brief Report.

Background:People with Alzheimer’s disease (AD) report pain less frequently and receive less pain medication than people without AD. Recent studies have begun to elucidate how pain may be altered in those with AD. However, potential sex differences in pain responsiveness have never been explored in these patients. It is unclear whether sex differences found in prior studies of healthy young and older individuals extend to people with AD.Objective:The purpose of this study was to examine sex differences in the psychophysical response to experimental thermal pain in people with AD.Methods:Cross-sectional analysis of 14 male and 14 female age-matched (≥65 years of age, median = 74) and AD severity-matched (Mini-Mental State Exam score <24, median = 16) communicative people who completed thermal psychophysics.Results:There was a statistically significant main effect of sex for both temperature and unpleasantness ratings that persisted after controlling for average and current pain (mixed-effects general liner model: temperature: p = 0.004, unpleasantness: p < 0.001). Females reported sensing mild pain and moderate pain percepts at markedly lower temperatures than did males (mild: Cohen’s d = 0.72, p = 0.051, moderate: Cohen’s d = 0.80, p = 0.036). By contrast, males rated mild and moderate thermal pain stimuli as more unpleasant than did females (mild: Cohen’s d = 0.80, p = 0.072, moderate: Cohen’s d = 1.32, p = 0.006). There were no statistically significant correlations of temperature with perceived unpleasantness for mild or moderate pain (rs = 0.29 and rs = 0.20 respectively, p > 0.05).Conclusions:Results suggest experimental pain-related sex differences persist in older adults with AD in a different manner than those previously demonstrated in cognitively intact older adults. These findings could potentially aid in developing targeted pain management approaches in this vulnerable population. Further studies are warranted to replicate the findings from this pilot work.

Thermal Stimulation Changes Diffusivity of the Spinothalamic Tract

Study Design.An experimental study.Objective.This study aimed to investigate task-dependent changes in fractional anisotropy (FA) within the spinal cord during painful stimulation.Summary of Background Data.Earlier experiments by Mandl et al (2008, 2013) used non-invasive functional diffusion tensor imaging (fDTI) to detect white matter fibers that were active during functional tasks. In two studies, it was observed that FA of involved white matter tracts exhibited repeatable task-related increases. In this study, we attempted to extend the fDTI work in the spinal cord.Methods.Twenty-three healthy, right-handed men (mean age 22 yrs, standard deviation [SD] = 4) were invited to participate in this study. Diffusion-weighted images were collected over spinal levels C2 to T4 during a painful thermal stimulus applied to the left thenar eminence. In order to investigate task-related activity, FA values within the contralateral (right) spinothalamic tract were analyzed using a generalized estimating equations (GEE) procedure. As a control, we also examined activity in the ipsilateral and contralateral corticospinal tracts, which are not considered to be involved in nociception.Results.Significant task-related decreases in FA were observed in the right spinothalamic tract at vertebral levels C2–C5 (Wald X2(1) = 17.754, P < 0.001). There was no change in control regions at levels C7–T2 of the same tract, which are located below the level of input from dermatome C6, Wald X2(1) = 0.185, P = 0.667. Results in all other regions assessed, that is, the left spinothalamic tract and bilateral corticospinal tract, were also not significant (P > 0.05).Conclusion.The current findings suggest that task-related changes in FA associated with the transmission of pain signals along the spinal cord can be detected using fDTI. We observed decreased FA values in the contralateral (right) spinothalamic tract following painful stimulation, while no such activity was apparent in control regions.Level of Evidence: 5

Offset analgesia: The role of peripheral and central mechanisms.

Offset Analgesia (OA) can be evoked by a three-heat-stimulus train (T1-T2-T3), with T1 (5s) and T3 (20s) having the same temperature (e.g. 48°C) and T2 (5s) being slightly higher (1-3°C). OA is defined as a disproportional pain reduction caused by the slight temperature decrease from T2 to T3. As the pain modulatory mechanisms behind OA are still poorly understood, the current study aimed to investigate the role of peripheral and central mechanisms by applying heat stimuli to the same location and to different unilateral and bilateral locations. Young healthy volunteers participated in the study. A 'standard-OA' paradigm (48-49-48°C) was applied to the non-dominant volar forearm (T1-T2-T3 applied on the same location). 'Unilateral-OA' trials were applied on three different locations of the non-dominant volar forearm (the same dermatome). 'Bilateral-OA' trials were applied by shifting T1-T2-T3 between dominant and non-dominant volar forearms. A constant stimulus of 48°C was applied as control for the evoked pain. The pain intensities were continuously recorded using an electronic visual analogue scale. The largest pain intensity reduction was reported for the 'standard-OA' paradigm (p<0.001) compared with the control stimulus. Both 'Unilateral-OA' and 'Bilateral-OA' trials caused a significant pain reduction (p<0.05) compared with the control; however, the pain reduction was less than that evoked by 'standard-OA' (p<0.05). This study showed that OA could be elicited when the stimuli were applied both to the same and to different locations (ipsi- and contralateral) indicating that peripheral as well as central mechanisms are involved in mediating OA. This study investigated offset analgesia by applying thermal painful stimuli to the ipsi- and bilateral forearms in healthy subjects and found that both peripheral and central mechanisms seem to mediate offset analgesia.

Hypnotic analgesia reduces brain responses to pain seen in others

Brain responses to pain experienced by oneself or seen in other people show consistent overlap in the pain processing network, particularly anterior insula, supporting the view that pain empathy partly relies on neural processes engaged by self-nociception. However, it remains unresolved whether changes in one’s own pain sensation may affect empathic responding to others’ pain. Here we show that inducing analgesia through hypnosis leads to decreased responses to both self and vicarious experience of pain. Activations in the right anterior insula and amygdala were markedly reduced when participants received painful thermal stimuli following hypnotic analgesia on their own hand, but also when they viewed pictures of others’ hand in pain. Functional connectivity analysis indicated that this hypnotic modulation of pain responses was associated with differential recruitment of right prefrontal regions implicated in selective attention and inhibitory control. Our results provide novel support to the view that self-nociception is involved during empathy for pain, and demonstrate the possibility to use hypnotic procedures to modulate higher-level emotional and social processes.

Effects of explicit cueing and ambiguity on the anticipation and experience of a painful thermal stimulus.

Many factors can influence the way in which we perceive painful events and noxious stimuli, but less is known about how pain perception is altered by explicit knowledge about the impending sensation. This study aimed to investigate the impact of explicit cueing on anxiety, arousal, and pain experience during the anticipation and delivery of noxious thermal heat stimulations. Fifty-two healthy volunteers were randomised to receive explicit instructions about visual cue-stimulus temperature pairings, or no explicit instructions about the cue-stimulus pairs. A pain anxiety task was used to investigate the effects of explicit cueing on anticipatory anxiety, pain experience and electrophysiological responses. Participants who received explicit instructions about the cue-stimulus pairs (i.e., the relationship between the colour of the cue and the temperature of the associated stimuli) reported significantly higher subjective anxiety prior to the delivery of the thermal heat stimuli (p = .025, partial eta squared = .10). There were no effects of explicit cueing on subsequent pain intensity, unpleasantness, or the electrophysiological response to stimulus delivery. The perceived intensity and unpleasantness of the stimuli decreased across the blocks of the paradigm. In both groups anticipating the ambiguous cue elicited the largest change in electrophysiological arousal, indicating that not knowing the impending stimulus temperature led to increased arousal, compared to being certain of receiving a high temperature thermal stimulus (both p < .001). Perceived stimulus intensity varied between ambiguous and non-ambiguous cues, depending on the temperature of the stimulus. Together these findings highlight the impact and importance of explicit cueing and uncertainty in experimental pain studies, and how these factors influence the way healthy individuals perceive and react to noxious and innocuous thermal stimuli.

Individuals with sickle cell disease have a significantly greater vasoconstriction response to thermal pain than controls and have significant vasoconstriction in response to anticipation of pain.

The painful vaso-occlusive crises (VOC) that characterize sickle cell disease (SCD) progress over hours from the asymptomatic steady-state. SCD patients report that VOC can be triggered by stress, cold exposure, and, pain itself. We anticipated that pain could cause neural-mediated vasoconstriction, decreasing regional blood flow and promoting entrapment of sickle cells in the microvasculature. Therefore, we measured microvascular blood flow in the fingers of both hands using plethysmography and laser-Doppler flowmetry while applying a series of painful thermal stimuli on the right forearm in 23 SCD patients and 25 controls. Heat pain applied to one arm caused bilateral decrease in microvascular perfusion. The vasoconstriction response started before administration of the thermal pain stimulus in all subjects, suggesting that pain anticipation also causes significant vasoconstriction. The time delay between thermal pain application and global vasoconstriction ranged from 5 to 15.5 seconds and increased with age (P < .01). Although subjective measures, pain threshold and pain tolerance were not different between SCD subjects and controls, but the vaso-reactivity index characterizing the microvascular blood flow response to painful stimuli was significantly higher in SCD patients (P = .0028). This global vasoconstriction increases microvascular transit time, and may promote entrapment of sickle cells in the microvasculature, making vaso-occlusion more likely. The rapidity of the global vasoconstriction response indicates a neural origin that may play a part in the transition from steady-state to VOC, and may also contribute to the variability in VOC frequency observed in SCD patients.

Influence of pain on motor preparation in the human brain.

The protective function of pain depends on appropriate motor responses to avoid injury and promote recovery. The preparation and execution of motor responses is thus an essential part of pain. However, it is not yet fully understood how pain and motor processes interact in the brain. Here we used electroencephalography to investigate the effects of pain on motor preparation in the human brain. Twenty healthy human participants performed a motor task in which they performed button presses to stop increasingly painful thermal stimuli when they became intolerable. In another condition, participants performed button presses without concurrent stimulation. The results show that the amplitudes of preparatory event-related desynchronizations at alpha and beta frequencies did not differ between conditions. In contrast, the amplitude of the preparatory readiness potential was reduced when a button press was performed to stop a painful stimulus compared with a button press without concomitant pain. A control experiment with nonpainful thermal stimuli showed a similar reduction of the readiness potential when a button press was performed to stop a nonpainful thermal stimulus. Together, these findings indicate that painful and nonpainful thermal stimuli can similarly influence motor preparation in the human brain. Pain-specific effects on motor preparation in the human brain remain to be demonstrated.NEW & NOTEWORTHY Pain is inherently linked to motor processes, but the interactions between pain and motor processes in the human brain are not yet fully understood. Using electroencephalography, we show that pain reduces movement-preparatory brain activity. Further results indicate that this effect is not pain specific but independent of the modality of stimulation.

Disrupted offset analgesia distinguishes patients with chronic pain from healthy controls.

Offset analgesia (OA) represents a disproportionately large decrease of pain perception after a brief, temporary increment of thermal pain stimulus and was reported attenuated in patients with neuropathic pain. We examined whether OA depends on the increment duration before offset, and whether individual features of OA distinguish patients with chronic pain and healthy controls. We used a Peltier-type thermal stimulator and OA paradigms including 5-, 10-, or 15-s duration of 1°C-increment (T2) over 45°C. We first examined OA response, on the left volar forearm, at 3 different T2's in 40 healthy volunteers, and OA and constant stimulus responses in 12 patients with chronic pain and 12 matched healthy controls. We measured magnitude of OA ([INCREMENT]OA) and maximum visual analogue scale (VAS) latency (time to peak VAS) during constant stimulus for each individual. Pain perception kinetics were compared with analysis of variance and sought for correlations with psychophysical parameters with a significance threshold at P < 0.05. In healthy controls, longer T2 at 10 or 15 seconds resulted in larger [INCREMENT]OA compared with T2 at 5 seconds (P = 0.04). In patients, [INCREMENT]OA was significantly smaller than controls at T2 = 5 or 10 seconds (P < 0.05) but grew comparable at T2 = 15 seconds with controls. Maximum VAS latency was longer in patients than in controls and negatively correlated with [INCREMENT]OA in patients. An OA index ([INCREMENT]OA/[maximum VAS latency]) proved diagnostic of chronic pain with an area under the receiver operating characteristic curve at 0.897. Patients with chronic pain showed impairment of OA and reduced temporal sharpening of pain perception, which might imply possible disturbance of the endogenous pain modulatory system.

A mass spectrometer for pain-response monitoring in rats

A mass spectrometer with a membrane interface has been used for measuring the relative concentration of carbon dioxide (CO2) released from rat skin in response to thermal irritation and pain stimulus during intraperitoneal propofol–lidocaine anesthesia. It is established that the local anesthetic lidocaine directly influences the central nervous system and induces antinociceptive reaction to thermal irritation.

Morphine responsiveness to thermal pain stimuli is aging-associated and mediated by dopamine D1 and D3 receptor interactions

Morphine actions involve the dopamine (DA) D1 and D3 receptor systems (D1R and D3R), and the responses to morphine change with age. We here explored in differently aged wild-type (WT) and D3R knockout mice (D3KO) the interactions of the D1R/D3R systems with morphine in vivo at three different times of the animals’ lifespan (2months, 1year, and 2years). We found that: (1) thermal pain withdrawal reflexes follow an aging-associated phenotype, with relatively longer latencies at 2months and shorter latencies at 1year, (2) over the same age range, a dysfunction of the D3R subtype decreases reflex latencies more than aging alone, (3) morphine altered reflex responses in a dose-dependent manner in WT animals and changed at its higher dose the phenotype of the D3KO animals from a morphine-resistant state to a morphine-responsive state, (4) block of D1R function had an aging-dependent effect on thermal withdrawal latencies in control animals that, in old animals, was stronger than that of low-dose morphine. Lastly, (5) block of D1R function in young D3KO animals mimicked the behavioral phenotype observed in the aged WT. Our proof-of-concept data from the rodent animal model suggest that, with age, block of D1R function may be considered as an alternative to the use of morphine, to modulate the response to painful stimuli.

Opposite patterns of change in perception of imagined and physically induced pain over the course of repeated thermal stimulations.

Individuals frequently show habituation to repeated noxious heat. However, given the defensive function of human pain processing, it is reasonable to assume that individuals anticipate that they would become increasingly sensitive to repeated thermal pain stimuli. No previous studies have, however, been addressed to this assumption. Therefore, in the current study, we investigated how healthy human individuals imagine the intensity of repeated thermal pain stimulations, and compared this with the intensity ratings given after physically induced thermal pain trials. Healthy participants (N=20) gave pain intensity ratings in two conditions: imagined and real thermal pain. In the real pain condition, thermal pain stimuli of two intensities (minimal and moderate pain) were delivered in four consecutive trials. The duration of the peak temperature was 20s, and stimulation was always delivered to the same location. In each trial, participants rated the pain intensity twice, 5 and 15s after the onset of the peak temperature. In the imagined pain condition, participants were subjected to a reference pain stimulus and then asked to imagine and rate the same sequence of stimulations as in the induced pain condition. Ratings of imagined pain and physically induced pain followed opposite courses over repeated stimulations: Ratings of imagined pain indicated sensitization, whereas ratings for physically induced pain indicated habituation. The findings were similar for minimal and moderate pain intensities. The findings suggest that, rather than habituating to pain, healthy individuals imagine that they would become increasingly sensitive to repeated thermal pain stimuli. This study identified opposite patterns of change in perception of imagined pain (sensitization) and physically induced pain (habituation). The findings show that individuals anticipate that they would become increasingly sensitive to repeated pain stimuli, which might also have clinical implications.

Orbitofrontal cortex mediates pain inhibition by monetary reward.

Pleasurable stimuli, including reward, inhibit pain, but the level of the neuraxis at which they do so and the cerebral processes involved are unknown. Here, we characterized a brain circuitry mediating pain inhibition by reward. Twenty-four healthy participants underwent functional magnetic resonance imaging while playing a wheel of fortune game with simultaneous thermal pain stimuli and monetary wins or losses. As expected, winning decreased pain perception compared to losing. Inter-individual differences in pain modulation by monetary wins relative to losses correlated with activation in the medial orbitofrontal cortex (mOFC). When pain and reward occured simultaneously, mOFCs functional connectivity changed: the signal time course in the mOFC condition-dependent correlated negatively with the signal time courses in the rostral anterior insula, anterior-dorsal cingulate cortex and primary somatosensory cortex, which might signify moment-to-moment down-regulation of these regions by the mOFC. Monetary wins and losses did not change the magnitude of pain-related activation, including in regions that code perceived pain intensity when nociceptive input varies and/or receive direct nociceptive input. Pain inhibition by reward appears to involve brain regions not typically involved in nociceptive intensity coding but likely mediate changes in the significance and/or value of pain.

Pilot Study of Functional Magnetic Resonance Imaging Responses to Somatic Pain Stimuli in Youth With Functional and Inflammatory Gastrointestinal Disease.

Brain-gut axis signaling modifies gastrointestinal symptomatology. Altered neural processing of intestinal pain signals involves interoceptive brain regions in adults with functional and inflammatory gastrointestinal disorders. Although these disorders frequently present in childhood, there are no published studies in youth. We determined whether neural processing of somatic pain stimuli differs in adolescents and young adults (AYA) with irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD), as compared to healthy controls (HC). IBS and IBD AYA (16-20 years) underwent anticipated and thermal pain stimuli of low and high intensity on their forearm and simultaneous blood oxygen level-dependent functional magnetic resonance imaging. Data from adult HC were used for comparison. Subjects answered surveys evaluating alexithymia, anxiety, depression, and pain catastrophizing. Group data were compared using linear mixed effects and analysis of variance. Study groups were similar by sex but not age. Significant group by pain condition interactions were observed in interoceptive brain regions during pain anticipation, and within perceptual brain regions during perceived pain. Higher activation within interoceptive brain regions during anticipated pain was observed in IBS compared with IBD and HC subjects. IBD patients demonstrated increased activation in perceptual brain regions during experienced pain as compared to IBS and HC. IBS and IBD AYA demonstrate altered neural processing of somatic pain compared with each other and with HC. Our results suggest that neuromodulatory interventions targeting interoceptive brain circuits in IBS and perceptual brain regions in IBD may be effective.

High Frequency Migraine Is Associated with Lower Acute Pain Sensitivity and Abnormal Insula Activity Related to Migraine Pain Intensity, Attack Frequency, and Pain Catastrophizing.

Migraine is a pain disorder associated with abnormal brain structure and function, yet the effect of migraine on acute pain processing remains unclear. It also remains unclear whether altered pain-related brain responses and related structural changes are associated with clinical migraine characteristics. Using fMRI and three levels of thermal stimuli (non-painful, mildly painful, and moderately painful), we compared whole-brain activity between 14 migraine patients and 14 matched controls. Although, there were no significant differences in pain thresholds nor in pre-scan pain ratings to mildly painful thermal stimuli, patients did have aberrant suprathreshold nociceptive processing. Brain imaging showed that, compared to controls, patients had reduced activity in pain modulatory regions including left dorsolateral prefrontal, posterior parietal, and middle temporal cortices and, at a lower-threshold, greater activation in the right mid-insula to moderate pain vs. mild pain. We also found that pain-related activity in the insula was associated with clinical variables in patients, including associations between: bilateral anterior insula and pain catastrophizing (PCS); bilateral anterior insula and contralateral posterior insula and migraine pain intensity; and bilateral posterior insula and migraine frequency at a lower-threshold. PCS and migraine pain intensity were also negatively associated with activity in midline regions including posterior cingulate and medial prefrontal cortices. Diffusion tensor imaging revealed a negative correlation between fractional anisotropy (a measure of white matter integrity; FA) and migraine duration in the right mid-insula and a positive correlation between left mid-insula FA and PCS. In sum, while patients showed lower sensitivity to acute noxious stimuli, the neuroimaging findings suggest enhanced nociceptive processing and significantly disrupted modulatory networks, particularly involving the insula, associated with indices of disease severity in migraine.

Preserved Capacity for Placebo Analgesia in the Elderly.

In contrast to the commonly shared view that endogenous pain modulation declines with age we found a comparable capacity for placebo analgesia in a group of healthy older and younger adults.

Abstract PR334

Background & Objectives: Up to 24% of patient post hysterectomy in KK Women’s and Children’s Hospital in Singapore end up with chronic pain. This study aims to evaluate cerebral blood flow (CBF) changes in the pain network using Arterial Spin Labelling (ASL), a non-invasive MRI technique able to quantify tissue perfusion, in women post hysterectomy when they are subjected to a painful thermal stimulus. Materials & Methods: This study was approved by the institutional review board and written consent was obtained. Pain-free women post hysterectomy (aged 38 to 67 years; average 49.7 years; median 48 years) were invited for MRI brain imaging on a 3T MR scanner with a 32-channel phased-array receive-only head coil. All subjects had 44 degrees of heat applied to the left thigh via a thermode during the MRI ASL scan. Subject’s pain score during the pain stimulation process was continuously recorded by Computerized Visual Analog Scale (COVAS). Significant pain experience was defined as more than 30% increase in pain score on the COVAS system. During the thermal stimulation, a total of 81 pairs of control-labelled ASL images were acquired using 3D-PASL sequence with temporal resolution of 8 seconds for each pair. Heat stimulation was applied for the 8th to 59th pairs of control-labelled images, while the first 7 pairs and the last 22 pairs of control-labelled images were obtained without heat stimulation. Results: Nineteen women underwent the MRI scans with 44 degrees thermal stimulation successfully. Seven women experienced significant pain as captured on the COVAS system during the pain stimulation process, while 12 did not experience significant pain. Significantly increased CBF was reflected in the pain network centres in all who experienced pain on COVAS. Those who did not experience pain on COVAS only had significant increased CBF in the right insula and cingulate. There was only statistical difference in the thalamus (p=0.03), post central gyrus (p=0.04) and frontal pole (p=0.04) when the CBF changes in the pain network were compared between those who experienced significant pain against those who did not. Conclusion: In women subjected to heat/pain stimulus, ASL is able to demonstrate statistically significant increased CBF in the thalamus, post central gyrus and frontal pole which matches the subjective pain experienced by the patient as captured on COVAS score. The relatively increased CBF experienced in the right thalamus and right insula would correspond to the heat thermode being placed on the left thigh.