Painful Heat Stimuli Research Articles

Sex and Gender are Not the Same: Why Identity Is Important for People Living with HIV and Chronic Pain.

BackgroundSex differences in pain sensitivity have been well documented, such that women often report greater sensitivity than men. However, clinical reports highlighting sex differences often equate gender and sex. This is a particularly critical oversight for those whose gender identity is different than their genetic sex.MethodsThis preliminary study sets to analyze differences in pain responses between cisgender and transgender individuals living with HIV and chronic pain. A total of 51 African-American participants (24 cisgender men, 20 cisgender women, 7 transgender women) with similar socioeconomic status were recruited. Genetic sex, gender identity, depression and anxiety, pain severity, pain interference and pain-related stigma were recorded. Participants also completed a quantitative sensory testing battery to assess pain in response to noxious heat and mechanical stimuli.ResultsTransgender women and cisgender women demonstrated a greater magnitude of temporal summation for heat pain stimuli or mechanical stimuli compared to cisgender men. Specifically, transgender women reported greater mechanical summation than either cisgender women or cisgender men. Transgender women and cisgender women similarly reported greater chronic pain severity compared to cisgender men.ConclusionThese data support the notion that gender identity may play a more significant role in pain sensation than genetic sex. These results further maintain that not only gender identity and genetic sex are distinct variables but that treatment should be based on identity as opposed to genetic sex.

Can Slow Deep Breathing Reduce Pain? An Experimental Study Exploring Mechanisms

Slow deep breathing (SDB) is commonly employed in the management of pain, but the underlying mechanisms remain equivocal. This study sought to investigate effects of instructed breathing patterns on experimental heat pain and to explore possible mechanisms of action. In a within-subject experimental design, healthy volunteers (n = 48) performed 4 breathing patterns: 1) unpaced breathing, 2) paced breathing (PB) at the participant's spontaneous breathing frequency, 3) SDB at 6 breaths per minute with a high inspiration/expiration ratio (SDB-H), and 4) SDB at 6 breaths per minute with a low inspiration/expiration ratio (SDB-L). During presentation of each breathing pattern, participants received painful heat stimuli of 3 different temperatures and rated each stimulus on pain intensity. Respiration, heart rate, and blood pressure were recorded. Compared to unpaced breathing, participants reported less intense pain during each of the 3 instructed breathing patterns. Among the instructed breathing patterns, pain did not differ between PB and SDB-H, and SDB-L attenuated pain more than the PB and SDB-H patterns. The latter effect was paralleled by greater blood pressure variability and baroreflex effectiveness index during SDB-L. Cardiovascular changes did not mediate the observed effects of breathing patterns on pain. PerspectivesSDB is more efficacious to attenuate pain when breathing is paced at a slow rhythm with an expiration that is long relative to inspiration, but the underlying mechanisms remain to be elucidated.

Heat pain modulation with virtual water during a virtual hand illusion

Immersive virtual reality is a powerful method to modify the environment and thereby influence experience. The present study used a virtual hand illusion and context manipulation in immersive virtual reality to examine top-down modulation of pain. Participants received painful heat stimuli on their forearm and placed an embodied virtual hand (co-located with their real one) under a virtual water tap, which dispensed virtual water under different experimental conditions. We aimed to induce a temperature illusion by a red, blue or white light suggesting warm, cold or no virtual water. In addition, the sense of agency was manipulated by allowing participants to have high or low control over the virtual hand’s movements. Most participants experienced a thermal sensation in response to the virtual water and associated the blue and red light with cool/cold or warm/hot temperatures, respectively. Importantly, the blue light condition reduced and the red light condition increased pain intensity and unpleasantness, both compared to the control condition. The control manipulation influenced the sense of agency, but did not influence pain ratings. The large effects revealed in our study suggest that context effects within an embodied setting in an immersive virtual environment should be considered within VR based pain therapy.

Synchronous Stimulation With Light and Heat Induces Body Ownership and Reduces Pain Perception

In this study, we investigated whether illusionary body ownership over artificial hands and non-corporeal objects modulates pain perception. Previous research has yielded to mixed results, but has separated painful stimulation used to test pain perception from the stimulation that was used to induce the illusion. Here, we used a variant of the rubber hand illusion (RHI) paradigm and induced the illusion directly via a combination of visual and painful stimuli. We presented heat pain stimuli at the real hand and visual stimuli beneath a rubber hand (part1), or a glass ball (part2). Illusion ratings were higher and pain ratings were lower in the synchronous compared to the asynchronous condition in both parts of the experiment. This study demonstrated the successful induction of a body illusion using a new visual–thermal method with painful stimuli. We showed that the RHI and interestingly also the glass ball has an analgesic effect on the perception of the heat pain stimuli. Our data suggests that induced ownership over artificial limbs but also over non-corporeal objects can reduce the perceived pain perception. This might be mediated via a partial referral of the perceived location of pain or respectively a distribution of pain over 2 locations. PerspectiveThis article presents a new visual–thermal method with painful stimuli for the induction of the Rubber Hand Illusion. An illusionary body ownership over artificial hands and non-corporeal has an analgesic effects on the perception of pain. Similar approaches might be useful to alleviate chronic pain, but needs further testing.

Neural oscillations and connectivity characterizing the state of tonic experimental pain in humans.

Pain is a complex phenomenon that is served by neural oscillations and connectivity involving different brain areas and frequencies. Here, we aimed to systematically and comprehensively assess the pattern of neural oscillations and connectivity characterizing the state of tonic experimental pain in humans. To this end, we applied 10‐min heat pain stimuli consecutively to the right and left hand of 39 healthy participants and recorded electroencephalography. We systematically analyzed global and local measures of oscillatory brain activity, connectivity, and graph theory‐based network measures during tonic pain and compared them to a nonpainful control condition. Local measures showed suppressions of oscillatory activity at alpha frequencies together with stronger connectivity at alpha and beta frequencies in sensorimotor areas during tonic pain. Furthermore, sensorimotor areas contralateral to stimulation showed significantly increased connectivity to a common area in the medial prefrontal cortex at alpha frequencies. Together, these observations indicate that the state of tonic experimental pain is associated with a sensorimotor‐prefrontal network connected at alpha frequencies. These findings represent a step further toward understanding the brain mechanisms underlying long‐lasting pain states in health and disease.

Deficient Inhibitory Endogenous Pain Modulation Correlates With Periaqueductal Gray Matter Metabolites During Chronic Whiplash Injury.

This study examined predictive correlations between periaqueductal gray (PAG) and anterior cingulate cortex (ACC) metabolite levels with deficient inhibitory endogenous pain modulation (EPM), including sensory and affective measures of pain during chronic whiplash injury (WHI). Healthy patients, and participants with chronic WHI, without (WHI-noP) or with pain (WHI-P), were screened with the Douleur Neuropathique 4 tool (DN4). EPM was assessed with C6 tonic heat pain stimuli with a Conditioned Pain Modulation (CPM) protocol. Magnetic resonance spectroscopy quantified ACC and PAG metabolite levels. WHI-P participants were characterized with high pain intensity and interference, and lower quality of life scores, compared with WHI-noP. Inhibitory CPM at 30 seconds was identified in the healthy noninjured (-45±16%; P<0.001) and WHI-noP groups (-36±8%; P<0.001). However, inhibitory EPM was not detected in the WHI-P group (-25±15%; P=0.06). Best fit and stepwise multiple regression revealed that the PAG glutamate/myoinositol metabolite ratio (P=0.01) and total creatine levels (P=0.02) predicted loss of EPM in the WHI-P group (r=0.71, α=0.97). Although myoinositol predicted loss of EPM in the ACC (P=0.04), this was below statistical power (r=0.31; α=0.56). The ACC N-acetyl-aspartate/myoinositol ratio (P=0.006) predicted chronic pain (DN4, r=0.53; α=0.87). The results of this study demonstrate deficient EPM at 30 seconds during tonic heat pain stimulation in WHI-P participants, compared with noninjured healthy volunteers or individuals with WHI-noP. In addition, quantification of PAG and ACC metabolites related to glutamate and glia predicted central chronic pain mechanisms related to loss of inhibitory EPM, while ACC metabolites characterized chronic pain described by descriptors and sensory changes.

Skin Conductance Response to Gradual-Increasing Experimental Pain.

Patient self-reporting of pain is not always possible, in those cases automated objective pain assessment could lead to reliable pain assessment. In this context, physiological measurements have been studied and one of the promising signals is skin conductance (SC). In this study, 1Hz SC signal acquisition is performed while gradually increasing heat and electrical pain stimuli are induced. Three labeled study periods are defined based on pain stimuli presence, self-reported pain threshold and pain tolerance. Different classification and regression models are compared, together with selected SC features. The model performances are evaluated using c-index. Results show good predictability, especially for the slow tonic component decomposed from the SC signal.

The relationship between sensitivity to pain and conditioned pain modulation in healthy people

BackgroundThe relationship between sensitivity to pain and conditioned pain modulation (CPM) – a paradigm reflecting the activity of the endogenous descending analgesic system - is still unclear. This study aimed at investigating CPM magnitude in two distinct subgroups of healthy subjects, presenting low vs. high sensitivity to pain (LSP vs. HSP, respectively), by employing two different thermal paradigms of CPM. MethodNinety-five healthy subjects (out of 293 tested) were identified as LSP (n = 48) or HSP (n = 47) according to their tolerance time to noxious cold stimulation (Cold Pressor Test, 1 °C). All subjects were exposed to two different paradigms of CPM: 1) Fixed temperature ‘test-pain’ (TP) where phasic, fixed painful heat stimuli of 47 °C were administered before and during a prolonged ‘conditioning stimulus’ (cold water at 12 °C for 30 s); and 2) Individually based 'pain-60' where TP was determined as the temperature that induced pain at a magnitude of 60 on a 0–100 rating scale (with the same conditioning stimulus). ResultUsing both thermal paradigms, LSP subjects showed decreased CPM magnitudes in comparison to HSP (p < 0.0001 in both paradigms). Within each group, no differences in the magnitudes of CPM were found between the two paradigms. ConclusionThese findings show that regardless of the thermal CPM paradigm employed, healthy individuals exhibiting low sensitivity to pain have a low pain inhibition profile and vice-versa. It is suggested that in healthy subjects, pain sensitivity predisposes the magnitude of CPM and not the other way around.

(265) The Relationship between Discrimination and Pain Tolerance and its Potential Mediation by Stress: Results from the Oklahoma Study of Native American Pain Risk (OK-SNAP)

Compared to other racial/ethnic minority groups, Native Americans (NAs) are more likely to report experiences of discrimination and also have the highest prevalence of pain conditions. Thus, there is a need to understand how and why these disproportionately high rates occur. Discrimination has been conceptualized within the biopsychosocial model as a chronic psychosocial stressor that can lead to dysfunction of regulatory processes, such as pain. A recent study found that perceived discrimination increased psychological distress that, in turn, led to increased chronic pain. To date, these relationships have not yet been evaluated in NAs. The present study examined perceived discrimination, stress, and pain tolerance in healthy, pain-free NAs (N=112) and NHWs (N=128). Discrimination was measured with the Everyday Discrimination Scale (EDS), stress was measured with the Perceived Stress Scale (PSS), and pain tolerance was measured in reaction to cold, heat, electrocutaneous, and ischemia pain stimuli. Results indicated NAs experienced more discrimination than NHWs (p

Sensory, Affective, and Catastrophizing Reactions to Multiple Stimulus Modalities: Results from the Oklahoma Study of Native American Pain Risk

Native Americans (NAs) have a higher prevalence of chronic pain than any other U.S. racial/ethnic group; however, little is known about the mechanisms for this pain disparity. This study used quantitative sensory testing to assess pain experience in healthy, pain-free adults (n = 137 NAs (87 female), n = 145 non-Hispanic whites (NHW; 68 female)) after painful electric, heat, cold, ischemic, and pressure stimuli. After each stimulus, ratings of pain intensity, sensory pain, affective pain, pain-related anxiety, and situation-specific pain catastrophizing were assessed. The results suggested that NAs reported greater sensory pain in response to suprathreshold electric and heat stimuli, greater pain-related anxiety to heat and ischemic stimuli, and more catastrophic thoughts in response to electric and heat stimuli. Sex differences were also noted; however, with the exception of catastrophic thoughts to cold, these finding were not moderated by race/ethnicity. Together, findings suggest NAs experience heightened sensory, anxiety, and catastrophizing reactions to painful stimuli. This could place NAs at risk for future chronic pain and could ultimately lead to a vicious cycle that maintains pain (eg, pain → anxiety/catastrophizing → pain). PerspectiveNAs experienced heightened sensory, anxiety, and catastrophizing reactions in response to multiple pain stimuli. Given the potential for anxiety and catastrophic thoughts to amplify pain, this characteristic may place them at risk for pain disorders and could lead to a vicious cycle that maintains pain.

Temporal Summation of Painful Heat Stimulation Is Facilitated in Trigeminal and Extratrigeminal Regions in Painful Myofascial Temporomandibular Disorders: Evidence from a Case-Control Study.

To determine whether patients with painful myofascial temporomandibular disorders (TMD) demonstrate facilitated temporal summation (TS) responses to painful heat stimuli applied to the painful trigeminal and extratrigeminal regions and whether there is a side difference in the trigeminal region for myofascial TMD pain patients compared to healthy controls. Twenty female Chinese myofascial TMD pain patients and 20 age-matched female volunteers participated in this case-control study. Thermal detection thresholds, thermal pain thresholds, and TS of 20 repetitive noxious thermal stimuli were measured on the skin above the masseter muscle on both sides and the thenar eminence of the less painful side/dominant hand. Numeric rating scale (NRS) scores of pain were provided after the 1st, 5th, 10th, 15th, and 20th stimuli, and TS was calculated as the highest NRS score minus the first NRS score in each test. Evidence of TS was found in the trigeminal and extratrigeminal regions for both groups, but with facilitated TS responses in myofascial TMD pain patients (P < .001). Within the myofascial TMD group and control group, there were no side-to-side differences (P > .289). Interestingly, the repetition of the TS test was associated with facilitated responses in myofascial TMD pain patients (P < .001). The current findings suggest TS of painful heat stimulation is facilitated in myofascial TMD pain patients with no side difference in the trigeminal region.

A test of positive suggestions about side effects as a way of enhancing the analgesic response to NSAIDs.

Side effects are frequent in pharmacological pain management, potentially preceding analgesia and limiting drug tolerability. Discussing side effects is part of informed consent, yet can favor nocebo effects. This study aimed to test whether a positive suggestion regarding side effects, which could act as reminders of the medication having been absorbed, might favor analgesia in a clinical interaction model. Sixty-six healthy males participated in a study “to validate pupillometry as an objective measure of analgesia”. Participants were unknowingly randomized double-blind to positive vs control information about side effects embedded in a video regarding the study drugs. Sequences of moderately painful heat stimuli applied before and after treatment with diclofenac and atropine served to evaluate analgesia. Atropine was deceptively presented as a co-analgesic, but used to induce side effects. Adverse events (AE) were collected with the General Assessment of Side Effects (GASE) questionnaire prior to the second induced pain sequence. Debriefing fully informed participants regarding the purpose of the study and showed them the two videos.The combination of medication led to significant analgesia, without a between-group difference. Positive information about side effects increased the attribution of AE to the treatment compared to the control information. The total GASE score was correlated with analgesia, i.e., the more AEs reported, the stronger the analgesia. Interestingly, there was a significant between-groups difference on this correlation: the GASE score and analgesia correlated only in the positive information group. This provides evidence for a selective link between AEs and pain relief in the group who received the suggestion that AEs could be taken as a sign “that help was on the way”. During debriefing, 65% of participants said they would prefer to receive the positive message in a clinical context. Although the present results cannot be translated immediately to clinical pain conditions, they do indicate the importance of testing this type of modulation in a clinical context.

The opioid receptor mu 1 (OPRM1) rs1799971 and catechol-O-methyltransferase (COMT) rs4680 as genetic markers for placebo analgesia

The placebo effect is considered the core example of mind-body interactions. However, individual differences produce large placebo response variability in both healthy volunteers and patients. The placebo response in pain, placebo analgesia, may be dependent on both the opioid system and the dopaminergic system. Previous studies suggest that genetic variability affects the function of these 2 systems. The aim of this study was therefore to address the interaction between the single nucleotide polymorphisms opioid receptor mu 1 (OPRM1) rs1799971 and catechol-O-methyltransferase (COMT) rs4680 on placebo analgesia. Two hundred ninety-six healthy volunteers participated in a repeated-measures experimental design where thermal heat pain stimuli were used as pain stimuli. Participants were randomized either to a placebo group receiving placebo cream together with information that the cream would reduce pain, or to a natural history group receiving the same pain stimuli as the placebo group without any application of cream or manipulation of expectation of pain levels. The results showed that the interaction between OPRM1 rs1799971 and COMT rs4680 was significantly associated with the placebo analgesic response. Participants with OPRM1 Asn/Asn combined with COMT Met/Met and Val/Met reported significant pain relief after placebo administration, whereas those with other combinations of the OPRM1 and COMT genotypes displayed no significant placebo effect. Neither OPRM1 nor COMT had any significant influence on affective changes after placebo administration. As shown in this study, genotyping with regard to OPRM1 and COMT may predict who will respond favorably to placebo analgesic treatment.

Fibromyalgia patients and healthy volunteers express difficulties and variability in rating experimental pain: a qualitative study.

Background and aims Despite the enormous body of literature spanning more than 50 years describing results of pain experiments, very few have used qualitative methods to explore subjects' thoughts while scoring experimental painful stimuli, and none in the available literature have used qualitative interviews to do so. The current study examined how participants in experimental pain research delineate pain ratings to better understand the unique influences of the experimental setting on pain scores. An additional aim was to highlight how individuals with fibromyalgia and healthy volunteers are differently influenced by characteristics of the experimental setting. Methods This was an inductive, qualitative study in which individual, semi-structured interviews were performed with 31 fibromyalgia patients and 44 healthy volunteers. Participants had taken part in a pain experiment during which a thermode was used to induce painful heat stimuli on two skin areas. There were two primary interview questions analyzed for this report: (1) "Thinking back to when you were getting the heat pain on your leg, what were you thinking about when deciding on your pain score?" and (2) Participants who said that it was difficult to decide on a pain score were asked to, "Describe what made it difficult to choose a number." Thematic analysis was used to generate conceptual categories from textual data and find common themes. Results Three notable differences were found between fibromyalgia patients and healthy volunteers: (1) using current daily pain as a benchmark was seen more in patients, (2) wanting to appear strong in front of the study investigators was more common in healthy volunteers, and (3) becoming mentally fatigued from rating many stimuli was more common for fibromyalgia patients. Thoughts while scoring pain included: (1) comparing with previous or current pain, (2) self-monitoring of one's ability to endure the pain, (3) focusing on the physical aspects of the pain, (4) knowing the experimental setting is safe, (5) focusing on the pain scale as an anchor, and (6) desire to appear strong. Additionally, five difficulties in scoring experimental pain were identified: (1) falling asleep, (2) mentally fatigued, (3) feeling as though they were guessing, (4) having to make a quick decision, and (5) difficulty in being consistent. Conclusions This study provides insights into the thoughts of participants in experimental pain research studies. Participants were distracted and influenced by the experimental setting and some factors differed for fibromyalgia patients versus healthy volunteers. Implications Understanding the ways in which the experimental setting influences pain ratings may help pain researchers better design and interpret studies. Researchers can use these findings to mitigate difficulties for participants in experimental research to add to its validity.

Effects of Electrical Transcutaneous Vagus Nerve Stimulation on the Perceived Intensity of Repetitive Painful Heat Stimuli: A Blinded Placebo- and Sham-Controlled Randomized Crossover Investigation.

Transcutaneous vagus nerve stimulation (TVNS) is a promising treatment for acute and chronic pain. However, experimental studies yielded controversial results. We examined if TVNS reduces the perceived intensity of repetitive painful heat stimulation and temporal summation of pain (TSP) in healthy volunteers in comparison with placebo and sham stimulation, as well as no intervention. In 4 sessions, 90 heat pulse stimuli at individual pain tolerance temperature were applied to the ventral forearm of 49 healthy volunteers (25 women) using a Contact Heat Evoked Potential Stimulator thermode (Medoc, Ramat Yishai, Israel). Pain intensity was assessed with verbal ratings on a numeric pain scale (0-100) at every tenth heat pulse. After the first session in which pain intensities without intervention were evaluated, participants completed 3 sessions in a single-blinded randomized crossover manner: (1) sham stimulation applied at the earlobes, (2) placebo stimulation (inactive device), or (3) TVNS applied at the cymbas conchae. Primary data were analyzed using analysis of variance for repeated measures and t test for paired samples. Pain intensity decreased during all interventions as compared to no intervention (ηp = 0.22, P < .001; mean difference TVNS versus no intervention 9.5; 95% confidence interval [CI], 3.6-15.4; P < .001). Hypoalgesic effect of TVNS was better than that of placebo and sham in men before the onset of TSP (mean differences for TVNS versus placebo 6.2; 95% CI, 0.2-12.1; TVNS versus sham 6.2; 95% CI, 0.2-12.1; P < .05). In women, TSP response under TVNS was decreased if compared to no intervention (median difference, 7.5; 95% CI, 3.5-15.0; P = .003). TVNS, placebo, and sham stimulation exerted comparable effects under experimental heat pain stimulation. Only in male participants, TVNS was superior to sham and placebo conditions in the reduction of heat pain before the onset of TSP.

The Opportunity to Avoid Pain May Paradoxically Increase Fear

Fear-avoidance models propose that pain-related fear may spur avoidance behavior leading to chronic pain disability. Pain-related fear elicits avoidance behavior, which is typically aimed at reducing fear. We hypothesized that engaging in avoidance may (paradoxically) increase rather than decrease pain-related fear (ie, bidirectionality hypothesis). In a between-subject design, participants (n = 64) were randomly assigned to the avoidance group or the control group. Avoidance group participants were led to believe they could avoid full exposure to a painful heat stimulus by pressing the stop button, whereas control group participants believed they were exposed to the full painful heat stimulus at all times. In reality and unknown to the participants, the intensity and duration of the heat stimulus was independent of the avoidance response, and was identical in both groups. During the test, the avoidance response (ie, pressing the stop button) was no longer available. As expected, pain-related fear levels were higher after avoiding the painful heat stimulus. Interestingly, in the avoidance group, pain-related fear increased after receiving instructions that avoidance would be possible, even before actually engaging in avoidance behavior. In the control group, no significant change was observed in pain-related fear throughout the experiment. The eyeblink startle measures did not corroborate this data pattern. PerspectiveThese observations provide partial support for the bidirectionality hypothesis between avoidance behavior and fear. These findings may have clinical implications and suggest that allowing avoidance behaviors during treatment may thwart fear reduction.

Women Undergoing Third Line Overactive Bladder Treatment Demonstrate Elevated Thermal Temporal Summation

We sought to determine whether women with overactive bladder who required third line therapy would demonstrate greater central sensitization, indexed by temporal summation to heat pain stimuli, than those with overactive bladder. We recruited 39 women with overactive bladder from the urology clinic who were planning to undergo interventional therapy for medication refractory overactive bladder with onabotulinumtoxinA bladder injection or sacral neuromodulation. We also recruited 55 women with overactive bladder who were newly seen at our urology clinic or who responded to advertisements for study participation. Participants underwent quantitative sensory testing using a thermal temporal summation protocol. The primary study outcome was the degree of temporal summation as reflected in the magnitude of positive slope of the line fit to the series of 10 stimuli at a 49C target temperature. We compared the degree of temporal summation between the study groups using linear regression. Women in the group undergoing third line therapy showed significantly higher standardized temporal summation slopes than those in the nontreatment group (β = 1.57, 95% CI 0.18-2.96, t = 2.25, p = 0.027). On exploratory analyses a history of incontinence surgery or hysterectomy was associated with significantly greater temporal summation. In this study the degree of temporal summation was elevated in women undergoing third line overactive bladder therapy compared to women with overactive bladder who were not undergoing that therapy. These findings suggest there may be pathophysiological differences, specifically in afferent nerve function and processing, in some women with overactive bladder.

S140. Altered brain activation in major depressive disorder during heat pain stimuli: An fMRI study

WHO predicts that major depressive disorder (MDD) will become the largest disease burden in the world by 2030. Studies have shown that about two-thirds of patients with MDD have painful somatic symptoms. The pathogenesis of MDD combined with pain is yet fully understood. The brain mechanism is the hotspot of current research. The brain activation areas were observed in patients with MDD (with pain or not) in our study, using the technology of contact heat stimulation combined with fMRI (CHS-fMRI). The purpose of this study is to explore the brain network related to pain in MDD, and further to provide useful information for the early diagnosis and treatment of MDD associated with pain. We recruited 42 untreated patients (meeting with the DSM-5 diagnostic criteria for MDD), who were assigned into two groups: pain group (MDDP group, 22 cases) and no pain group (MDDNP group, 20 cases), and 22 healthy volunteers were recruited as control group(HC group). Before the experiment, all subjects have completed the test of visual analogue scale (VAS) and the Mc-Gill pain questionnaire-2 (SF-MPQ-2). During the acquisition of fMRI, the right dorsal forearm received CHS in 51 degree. Finally, VAS was used to score the heat pain stimulation for each subject, as well as the quantitative sensory test (QST) of the contact heat stimulus site was performed. These activated brain areas in MDD group with statistical significance (P < 0.05) included bilateral cerebellum,vermis,right frontal cortex, right middle temporal gyrus, right thalamus, middle cingulate gyrus, and bilateral semioval center. These decreased activated brain areas in MDD group with statistical significance (P < 0.05) included bilateral hippocampus, bilateral amygdale, bilateral putamen, bilateral thalamus, bilateral insula, bilateral inferior frontal gyrus, right superior frontal gyrus, bilateral temporal lobe, and right calcarine. These activated brain areas in HC group with statistical significance (P < 0.05) included bilateral cerebellum, vermis, bilateral inferior frontal gyrus, right middle frontal gyrus, bilateral temporal lobe, bilateral inferior parietal lobule, left lingual gyrus, and left cuneus gyrus. These decreased activated brain areas in HC group with statistical significance (P < 0.05) included bilateral hippocampus, bilateral parahippocampal gyrus, bilateral middle temporal gyrus, bilateral amygdala, bilateral thalamus, bilateral putamen, bilateral insula, bilateral lingual gyrus, and right calcarine. The application of technology of CHS-fMRI is an ideal method for studying the network related to pain. There are abnormal activation of frontal-limbic region in MDDP group compared with MDDNP and HC group. Moreover, their activated area and activated intensity of activated brain regions are different. The network related to pain may change in MDD, which is worthy of further study.

Pain Modulation in Response to Resistance Exercise Training in Gulf War Veterans with Chronic Pain

United States military Veterans of the Persian Gulf War (GV) suffer unresolved chronic musculoskeletal pain (CMP) that significantly impacts their functional ability and quality of life. Pain modulation is impaired in some groups with CMP and can be augmented with acute exercise. Whether chronic exercise training influences pain modulation in GV with CMP is unknown. PURPOSE: To examine the effects of a 16-week resistance exercise training (RET) program on pain modulation in GV with CMP. METHODS: Forty GV with CMP were randomly assigned to RET (n=19) or a wait-list control group (WLC; n=21). The RET program was individualized to begin at a low intensity and involved standardized progression. Pain modulation was evaluated at baseline and 3 subsequent time points by comparing pain ratings to a series of painful heat stimuli delivered alone or concurrently with the Stroop color word task, which has two levels of cognitive difficulty: congruent (CS) and incongruent (IS). Variance to mean ratios (VMR) of pain modulation scores were calculated as an indicator of dispersion. Separate repeated measures MANOVA were used to examine the effect of group (RET vs. WLC) and time (1-4) on pain modulation (change in pain ratings) for both types of Stroop presentation. RESULTS: Groups did not differ on age, height, weight, or gender (p < 0.05). Whole body strength improved with training (average 1-RM% change from baseline across 10 upper & lower body exercises = 28.95%). No significant main or interaction effects were detected for either Stroop presentation (p > 0.05). The proportion of individuals demonstrating a pain modulatory response did not differ at any time point, X2 (1, N=40) = 0.14-2.10, p > 0.05. Pain modulation scores where highly variable for both groups across each time point (VMR Range: CS 1.77-1.96; IS 2.74-5.07). CONCLUSION: The degree to which GVs with CMP modulate pain at baseline does not appear to change as a result of RET, however pain modulation scores were highly variable across groups and time points. The lack of a change in pain modulation suggests that resistance exercise training in GVs with CMP does not influence the pain regulatory mechanism assessed here. Supported by US Department of Veterans Affairs grant #I01CX000383.

Verbal Instruction Can Induce Extinction of Fear of Movement-Related Pain

The fear avoidance model of chronic musculoskeletal pain highlights the importance of pain-related fear in chronification of pain. Although several interventions have been developed on the basis of this model, the following issues remain unresolved: first, whether movement conditioned to pain can evoke fear responses particularly sympathetic activation, and second, whether verbal instructions can attenuate conditioned fear of movement-related pain as with direct experience. To investigate these issues, we induced proprioceptive conditioning (learning the relationship between proprioceptive sensations and an aversive event) and extinction learning in healthy volunteers, and we compared psychophysiological and subjective indices of fear between an instructed and a normal extinction group. Using paired presentation of painful heat stimuli as an unconditioned stimulus and flexion of the wrist as a conditioned stimulus, all participants acquired the conditioned fear response (skin potential response) to the conditioned stimulus. The instructed extinction group was then told that the movement was no longer followed by painful stimulus at the beginning of the extinction phase, and only this group showed significant decreases on both indices of fear. This finding indicates that verbal instruction can attenuate conditioned fear of movement-related pain, supporting the clinical importance of providing information regarding the relationship between movement and pain. PerspectiveThis article presents evidence that, in a laboratory setting, verbal instructions rapidly decrease conditioned fear of movement-related pain on psychophysiological as well as subjective indices. This result indicates that it is important for chronic musculoskeletal pain patients to precisely understand the relationship between movement and pain in clinical situations.