Pain Inhibitory Processes Research Articles

High Body Mass Index Disrupts the Homeostatic Effects of Pain Inhibitory Control in the Symptomatology of Patients With Fibromyalgia

This study examines the influence of body mass index (BMI) on the relationship between quantitative sensory testing measures and clinical characteristics in fibromyalgia syndrome (FMS). Utilizing BMI as a categorical covariate (≥25 or ≥30 kg/m²) in associations between quantitative sensory testing metrics (pain-60, conditioned pain modulation, and temporal summation of pain [TSP]) and FMS clinical features, we explored BMI's role as both a confounder (change-in-estimate criterion—change equal or higher than 10%) and effect modifier (interaction term). Significant interactions revealed overweight/obese BMI as a modifier in the relationship between conditioned pain modification and both depression and symptom impact, with a homeostatic relationship between better clinical profile and pain inhibitory response observed solely in the normal-weight group. Similar results were found for pain-60 and depression. Additionally, BMI ≥30 kg/m² modified TSP's effect on pain, demonstrating lower pain with increased TSP, exclusively in the nonobese group. This study highlights the significant role of BMI in moderating the relationships of important pain inhibitory control processes and pain intensity, depression, and the overall impact of FMS symptoms. Our results suggest that high BMI states disrupt the homeostatic effects of pain inhibition, reducing its salutogenic response in FMS participants. We discuss the mechanistic and therapeutic implications of targeting BMI in FMS clinical trials and the potential impact of this important relationship. PerspectiveThis investigation highlights the disruptive influence of high BMI on pain inhibitory control in fibromyalgia, unbalancing clinical symptoms such as pain and depression. It underscores the necessity of integrating BMI considerations into therapeutic approaches to enhance pain management and patient outcomes.

Altered Endogenous Pain-Inhibitory Function in Older Adults With Chronic Pain Is Associated With Disruptions in Functional Connectivity During Resting State

Increasing research points to a decline in the ability to internally regulate pain as a contributing factor to the increased pain susceptibility in aging. This study investigated the connection between pain regulation and resting-state functional connectivity (rsFC) in older adults with chronic pain. We compared functional magnetic resonance imaging rsFC of 30 older adults with chronic pain (69.5 ± 6.58 years, 14 males), 29 pain-free older (70.48 ± 4.60, 15 males), and 30 younger adults (20.0 ± 1.58, 15 males). Pain inhibition and facilitatory capabilities were assessed using conditioned pain modulation (CPM) and temporal summation. Older adults with chronic pain displayed lower pain inhibition during the CPM than pain-free older and younger adults. rsFC analysis showed that older adults with chronic pain, in comparison with younger participants, displayed an abnormal hyperconnectivity between right dorsolateral prefrontal cortex and left amygdala, which was significantly correlated with lower pain inhibition during the CPM. Older adults with chronic pain displayed higher connectivity between the primary somatosensory cortex and nucleus accumbens than pain-free older adults. Finally, both older adult groups displayed reduced connectivity between brain structures involved in pain inhibition and processing in comparison with younger adults. Altogether, our results suggest that suffering from pain during aging leads to a dysfunction of pain-inhibitory processes, which significantly surpass those caused by normal aging. Furthermore, our results point to a key role of emotional and motivational brain areas, and their interaction with executive and somatosensory areas, in the reduced inhibitory capacity and likely the maintenance of chronic pain in aging. PerspectiveThis study examines the link between reduced pain-inhibition capacity and increased resting-state connectivity between affective, sensory, and executive brain structures in older adults with chronic pain. These findings could inform new pain assessment and treatment programs for this population.

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.

Family History of Alcohol Use Disorder as a Predictor of Endogenous Pain Modulation Among Moderate to Heavy Drinkers

Family history of alcohol use disorder (AUD) is frequently endorsed by persons with chronic pain. Although individuals with a family history of AUD have demonstrated enhanced sensitivity to painful stimulation, previous research has not examined endogenous pain modulation in this population. The goal of this study was to test family history of AUD as a predictor of conditioned pain modulation, offset analgesia, and temporal summation among a sample of moderate and heavy drinkers. Adults with no current pain (N = 235; 58.3% male; Mage = 34.3; 91.9% non-Hispanic; 60% white) were evaluated for family history of AUD at baseline and pain modulatory outcomes were assessed via quantitative sensory testing. Participants with a family history of AUD (relative to those without) evinced a pro-nociceptive pain modulation profile in response to experimental pain. Specifically, family history of AUD was associated with deficits in pain-inhibitory processes. Approximately 4% of the variance in endogenous pain modulation was accounted for by family history, and exploratory analyses suggested these effects may be driven by paternal AUD. PerspectiveThe current findings suggest individuals with a family history of AUD demonstrate pain modulatory function that may predispose them to the development of chronic pain. Clinically, these data may inform pain management approaches for individuals with a family history of AUD.

Does muscular or mental fatigue have an influence on the nociceptive flexion reflex? A randomized cross-over study in healthy people.

The nociceptive flexion reflex (NFR) is a spinally-mediated withdrawal reflex occurring in response to noxious stimuli and is used as an electrophysiological marker of spinal nociception. Although it is well-documented that the NFR is subject to powerful modulation of several personal factors, the effects of experimentally induced fatigue on the NFR have not yet been examined. Hence, this study aimed to characterize if and how fatigue affects spinal nociception in healthy adults. The NFR of 58 healthy people was measured prior to and following rest and two fatiguing tasks performed in randomized order. The NFR was elicited by transcutaneous electrical stimulation of the sural nerve and objectified by electromyographic recordings from the biceps femoris muscle. An isokinetic fatiguing protocol was used to induce localized muscle fatigue of the hamstrings. The modified incongruent Stroop-word task was used to provoke mental fatigue. A linear mixed model analysis was performed to assess the influence of fatigue on the NFR. Low-to-moderate levels experimentally induced localized muscle and mental fatigue did not affect the NFR in healthy adults. These results suggest that descending pain inhibitory processes to dampen spinal nociception are resistant to the effects of localized muscle and mental fatigue. The relative robustness of the NFR to fatigue may be beneficial in both clinical and research settings where the influence of confounders complicates interpretation. Furthermore, the findings possibly help enhance our understanding on why even demanding cognitive/physical exercise-based treatment programs form effective treatment strategies for patients with chronic pain. The present study unraveled that low-to-moderate levels experimentally induced localized muscle and mental fatigue did not affect the NFR. These results suggest that descending pain inhibitory processes to dampen spinal nociception are resistant to the effects of localized muscle and mental fatigue. This relative robustness of the NFR may be beneficial in a clinical setting in which the evaluation of spinal nociception that is unaffected by clinical symptoms of fatigue may be useful (e.g. chronic fatigue syndrome, cancer-related fatigue, etc.).

Conditioned Pain Modulation And Blood Pressure Responses To Cold Pressor Test Among Resistance Exercisers

Conditioned pain modulation (CPM) examines central pain inhibitory processing by assessing changes of sensitivity to the first pain stimulus after exposure to the second pain stimulus compared to baseline, and serves as risk factor of chronic pain. Aerobically-trained individuals typically show greater CPM compared to controls, but little is known regarding CPM among resistance exercisers (REs) who habitually engage in resistance exercise/strength training. REs often show elevated resting blood pressure (BP), which is associated with greater BP responses to cold pressor test (CPT) of immersing a hand into a cold water bath. Given past research showing the positive association between CPM and BP responses to CPT as the second pain stimulus, REs may exhibit greater CPM, along with augmented BP responses to CPT. PURPOSE: To compare CPM and BP responses to CPT between REs and controls. METHODS: REs were primarily recruited from weight lifting and power lifting teams (n = 15). Controls were healthy, normally active individuals (NAs) (n = 15). The participants completed the CPM test to evaluate changes in pain ratings (0-100) to electrical stimuli delivered to the ankle after CPT for a maximum of 2 minutes compared to baseline. The magnitude of CPM was calculated as change scores: post-CPT pain ratings - baseline pain ratings, with smaller pain ratings indicating greater pain inhibition. BP was assessed at baseline and every minute during CPT. CPM and BP data were analyzed using a mixed model ANOVA. The relationship between CPM and BP was tested using a correlational analysis. RESULTS: Each group consisted of young, 9 men and 6 women (REs: 23 ± 5 yrs vs. NAs: 22 ± 2 yrs, p > 0.05). REs reported spending 9.1 ± 4.5 hours/week for resistance exercise. REs and NAs exhibited comparable CPM (Change scores. REs: -12 ± 12 vs. NAs: -14 ± 12, p > 0.05), but REs showed greater systolic BP responses to CPT compared to NAs (Mean SBP. REs: 129 ± 11 mmHg vs. NAs: 119 ± 14 mmHg, p < 0.05). No significant association was found between systolic BP and CPM in REs (Resting: r = 0.2, p > 0.05 & Reactivity: r = -0.2, p > 0.05), but resting systolic BP was positively associated with CPM in NAs (Resting: r = 0.5, p < 0.05 & Reactivity: r = -0.1, p > 0.05). CONCLUSION: The role of BP in CPM is likely complex, and the potential role of exercise in central pain processing needs to be studied.

Comparable conditioned pain modulation and augmented blood pressure responses to cold pressor test among resistance exercisers compared to healthy controls

Conditioned pain modulation (CPM) test examines central pain inhibitory processing. Aerobically-trained individuals show greater CPM. However, there is a paucity of knowledge regarding CPM among resistance exercise-trained individuals, although regular engagement in resistance exercise may lead to greater CPM via augmented blood pressure (BP) responses during the CPM test. Therefore, the present study compared CPM and BP responses between resistance exercisers (REs) and controls (n = 15 per group). The participants completed the CPM test to evaluate changes in electrical pain ratings to the ankle after cold pressor test (CPT) consisting of immersing a hand into a cold water bath compared to baseline. REs and controls exhibited similar CPM, although REs showed greater systolic BP responses to CPT compared to controls. The results suggest that the role of BP in CPM is likely complex, and the role of exercise in central pain processing and cardiovascular system needs to be studied.

(200) A Pronociceptive Endogenous Pain Modulatory Balance in Persons Living with HIV and Chronic Pain

Chronic pain in persons living with HIV (PLWH) may be related to alterations in endogenous pain modulatory processes (e.g., high facilitation and low inhibition of nociception) that promote exaggerated pain responses, known as hyperalgesia and central nervous system sensitization. This observational study examined differences in endogenous pain modulatory processes between 59 PLWH with chronic pain, 51 PLWH without chronic pain, and 50 controls without HIV or chronic pain. Quantitative sensory testing for temporal summation (TS) of mechanical and heat pain as well as conditioned pain modulation (CPM) were used to assess endogenous pain facilitatory and inhibitory processes, respectively. Associations among TS, CPM, and self-reported clinical pain severity (Brief Pain Inventory-Short Form) were also examined in PLWH with chronic pain. Findings demonstrated significantly greater TS of mechanical (p

Enhanced facilitation and diminished inhibition characterizes the pronociceptive endogenous pain modulatory balance of persons living with HIV and chronic pain.

Chronic pain in persons living with HIV (PLWH) may be related to alterations in endogenous pain modulatory processes (e.g., high facilitation and low inhibition of nociception) that promote exaggerated pain responses, known as hyperalgesia, and central nervous system (CNS) sensitization. This observational study examined differences in endogenous pain modulatory processes between 59 PLWH with chronic pain, 51 PLWH without chronic pain, and 50 controls without HIV or chronic pain. Quantitative sensory testing for temporal summation (TS) of mechanical and heat pain as well as conditioned pain modulation (CPM) were used to assess endogenous pain facilitatory and inhibitory processes, respectively. Associations among TS, CPM, and self-reported clinical pain severity were also examined in PLWH with chronic pain. Findings demonstrated significantly greater TS of mechanical and heat pain for PLWH with chronic pain compared to PLWH without chronic pain and controls. CPM effects were present in controls, but not in either PLWH with or without chronic pain. Among PLWH with chronic pain, greater TS of mechanical pain was significantly associated with greater average clinical pain severity. Results of this study suggest that enhanced facilitation and diminished inhibition characterizes the pronociceptive endogenous pain modulatory balance of persons living with HIV and chronic pain.

(155) - State catastrophizing is associated with facilitation of spinal nociception during conditioned pain modulation (CPM)

Pain catastrophizing is associated with enhanced pain and also reduces the efficacy of pain inhibitory processes. Interestingly, prior work suggests pain catastrophizing does not exert its hyperalgesic effects via descending facilitation of spinal nociception, because several studies have failed to find a relation with the nociceptive flexion reflex (NFR, a physiological marker of spinal nociception). The present study further explored this issue by examining the relationship between situation-specific (state) pain catastrophizing and conditioned pain modulation (CPM) of pain ratings and the NFR in 198 healthy, pain-free participants. CPM was assessed from painful electric stimulations (test stimuli) delivered to the ankle before, during, and after participants placed their hand in painfully cold water (10°C; conditioning stimulus). Pain ratings and NFR magnitudes were assessed in response to test stimuli. Immediately following CPM, participants filled out the Pain Catastrophizing Scale with instructions to report on their catastrophic thoughts during the cold water. Three groups (low, medium, and high catastrophizing) were formed from their responses. Results found state catastrophizing did not influence CPM of pain ratings even though mean pain ratings varied linearly with catastrophizing (more catastrophizing = more pain). By contrast, CPM of NFR was influenced by catastrophizing such that significant inhibition of NFR was only observed in the low catastrophizing group. No NFR inhibition was found in the medium group and significant NFR facilitation was found in the high group. These findings imply that central modulatory mechanisms are altered by greater catastrophizing, shifting the balance toward descending facilitation during CPM and a generalized perceptual hyperalgesia. As such, individuals that catastrophize may be at risk for chronic pain.

Loss of Temporal Inhibition of Nociceptive Information Is Associated With Aging and Bodily Pain.

Older and middle-aged adults showed reduced offset analgesia compared with younger adults. The significant association between reduced offset analgesia and pain in daily life supports the notion that pain modulatory deficits are associated with not just a chronic pain condition but with the experience of pain in general.

Conditioned pain modulation among young, healthy, and physically active African American and non-Hispanic White adults

ObjectiveResearch shows that African American (AA) adults experience more severe and frequent pain compared to non-Hispanic White (NHW) adults. Additionally, experimental studies demonstrate that AA adults exhibit less efficient central pain inhibition compared to NHW adults, which may partially explain the racial/ethnic disparities in pain. Evidence suggests that regular physical activity (PA) may help improve central pain inhibition, but research shows that AA adults engage in less PA, and are less likely to meet PA guidelines for health promotion compared to NHW adults. These observations suggest that PA levels may help better understand the racial/ethnic difference in central pain inhibition. Therefore, this study compared central pain inhibition and PA levels among AA and NHW adults. MethodsYoung and healthy participants were recruited on campus, and 27 AA and 27 NHW adults completed this study. Central pain inhibitory processing was assessed using conditioned pain modulation (CPM), where changes in electrical pain ratings were quantified during and after exposure to pressure pain compared to baseline. PA levels were assessed using self-report questionnaires and accelerometer. ResultsThe participants were generally physically active, and most participants in both groups met the public recommendation of PA for health promotion. Electrical pain ratings were significantly reduced during and after exposure to pressure pain compared to baseline. There was no racial/ethnic difference in a magnitude of changes in electrical pain ratings. ConclusionYoung, healthy, and physically active AA and NHW adults exhibit similar CPM responses. Regular PA may help attenuate the racial/ethnic difference in CPM responses.

Physical activity behavior predicts endogenous pain modulation in older adults.

Older adults compared with younger adults are characterized by greater endogenous pain facilitation and a reduced capacity to endogenously inhibit pain, potentially placing them at a greater risk for chronic pain. Previous research suggests that higher levels of self-reported physical activity are associated with more effective pain inhibition and less pain facilitation on quantitative sensory tests in healthy adults. However, no studies have directly tested the relationship between physical activity behavior and pain modulatory function in older adults. This study examined whether objective measures of physical activity behavior cross-sectionally predicted pain inhibitory function on the conditioned pain modulation (CPM) test and pain facilitation on the temporal summation (TS) test in healthy older adults. Fifty-one older adults wore an accelerometer on the hip for 7 days and completed the CPM and TS tests. Measures of sedentary time, light physical activity (LPA), and moderate to vigorous physical activity (MVPA) were obtained from the accelerometer. Hierarchical linear regressions were conducted to determine the relationship of TS and CPM with levels of physical activity, while controlling for demographic, psychological, and test variables. The results indicated that sedentary time and LPA significantly predicted pain inhibitory function on the CPM test, with less sedentary time and greater LPA per day associated with greater pain inhibitory capacity. Additionally, MVPA predicted pain facilitation on the TS test, with greater MVPA associated with less TS of pain. These results suggest that different types of physical activity behavior may differentially impact pain inhibitory and facilitatory processes in older adults.

Endogenous inhibition of pain and spinal nociception in women with premenstrual dysphoric disorder.

PurposePremenstrual dysphoric disorder (PMDD) is characterized by severe affective and physical symptoms, such as increased pain, during the late-luteal phase of the menstrual cycle. The mechanisms underlying hyperalgesia in women with PMDD have yet to be identified, and supraspinal pain modulation has yet to be examined in this population. The present study assessed endogenous pain inhibitory processing by examining conditioned pain modulation (CPM, a painful conditioning stimulus inhibiting pain evoked by a test stimulus at a distal body site) of pain and the nociceptive flexion reflex (NFR, a spinally-mediated withdrawal reflex) during the mid-follicular, ovulatory, and late-luteal phases of the menstrual cycle.MethodsParticipants were regularly-cycling women (14 without PMDD; 14 with PMDD). CPM was assessed by delivering electrocutaneous test stimuli to the sural nerve before, during, and after a painful conditioning ischemia task. Participants rated their pain to electrocutaneous stimuli, and NFR magnitudes were measured. A linear mixed model analysis was used to assess the influence of group and menstrual phase on CPM.ResultsCompared with controls, women with PMDD experienced greater pain during the late-luteal phase and enhanced spinal nociception during the ovulation phase, both of which were independent of CPM. Both groups showed CPM inhibition of pain that did not differ by menstrual phase. Only women with PMDD evidenced CPM inhibition of NFR.ConclusionEndogenous modulation of pain and spinal nociception is not disrupted in women with PMDD. Additionally, greater NFR magnitudes during ovulation in PMDD may be due to tonically-engaged descending mechanisms that facilitate spinal nociception, leading to enhanced pain during the premenstrual phase.

Sex differences in experimental measures of pain sensitivity and endogenous pain inhibition.

It has been suggested that increased pain sensitivity and disruption of endogenous pain inhibitory processes may account, at least in part, for the greater prevalence and severity of chronic pain in women compared to men. However, previous studies addressing this topic have produced mixed findings. This study examined sex differences in pain sensitivity and inhibition using quantitative sensory testing (QST), while also considering the influence of other important factors such as depressive symptoms and sleep quality. Healthy men (n=24) and women (n=24) each completed a QST battery. This battery included an ischemic pain task (IPT) that used a submaximal effort tourniquet procedure as well as a conditioned pain modulation (CPM) procedure for the assessment of endogenous pain inhibition. Prior to QST, participants completed the Center for Epidemiologic Studies Depression Scale and the Pittsburgh Sleep Quality Index. Analyses revealed significant sex differences for the ischemic pain task and the conditioned pain modulation procedure, such that women tolerated the ischemic pain for a shorter amount of time and demonstrated less pain inhibition compared with men. This remained true even when accounting for sex differences in depressive symptoms and sleep quality. The results of this study suggest that women may be more pain sensitive and possess less-efficient endogenous pain inhibitory capacity compared with men. Whether interventions that decrease pain sensitivity and enhance pain inhibition in women ultimately improve their clinical pain outcomes is an area of research that deserves additional attention in the future.

(340) Intranasal oxytocin decreases anxiety and enhances endogenous pain inhibition

Preliminary evidence suggests that intranasal oxytocin may be a safe and effective analgesic with far reaching applicability. However, this limited previous research has lacked methodological rigor. A separate and stronger evidence base underscores the efficacy of intranasal oxytocin for alleviating anxiety while enhancing psychological well-being. Better understanding the role of oxytocin in endogenous pain modulation and pain-related mood states may highlight novel mechanisms associated with analgesia. The current study examined the effects of intranasal oxytocin administration on endogenous pain inhibitory processes as well as anxiety using a placebo-controlled, double-blind, within-subjects crossover design. Thus far, 24 of an expected 30 (38% female) pain-free, young adults have completed three laboratory sessions on three consecutive days. The first session represented the baseline assessment of endogenous pain inhibition via conditioned pain modulation (CPM). CPM was tested using algometry (test stimulus) and cold pressor (conditioning stimulus). During the second and third study sessions, participants initially completed the State-Trait Anxiety Inventory (STAI) and then self-administered a single (40IU/1mL) dose of placebo or intranasal oxytocin in random order. Thirty minutes following administration, participants again completed the STAI and repeated assessment of CPM. Results showed a non-significant decrease in anxiety following placebo administration (t23 = 1.14, p = .27); however, anxiety did significantly decrease following the administration of oxytocin (t23 = 2.32, p = .03). Further, there was a significant increase in CPM across the three study sessions (F2,46 = 3.94, p = .03). Specifically, CPM was significantly increased following administration of oxytocin relative to baseline (F1,23 = 5.57, p = .02). Although CPM was greater following administration of oxytocin compared to placebo, this difference was not statistically significant (F1,23 = 2.50, p = .13). These data tentatively suggest that the administration of intranasal oxytocin yields anxiolytic effects and also augments endogenous pain inhibitory capacity.

Using fMRI to evaluate the effects of milnacipran on central pain processing in patients with fibromyalgia

BackgroundIn recent years, the prescription of serotonin-noradrenalin reuptake inhibitors (SNRIs) for treatment of fibromyalgia (FM) has increased with reports of their efficacy. The SNRI milnacipran is approved by the U.S. Food and Drug Administration (FDA) for treatment of FM, yet, the mechanisms by which milnacipran reduces FM symptoms are unknown. A large number of neuroimaging studies have demonstrated altered brain function in patients with FM but the effect of milnacipran on central pain processing has not been investigated. The primary objective of this study was to assess the effect of milnacipran on sensitivity to pressure-evoked pain in FM. Secondary objectives were to assess the effect of milnacipran on cerebral processing of pressure-evoked pain using fMRI and the tolerability and safety of milnacipran 200mg/day in FM. Methods92 patients were randomized to either 13-weeks milnacipran treatment (200mg/day) or placebo in this double-blind, placebo-controlled multicenter clinical trial. Psychophysical measures and functional MRI (fMRI) assessments were performed before and after treatment using a computer-controlled pressure-pain stimulator. Here, we present the results of several a priori defined statistical analyses. ResultsMilnacipran-treated patients displayed a trend toward lower pressure-pain sensitivity after treatment, compared to placebo, and the difference was greater at higher pain intensities. A single group fMRI analysis of milnacipran-treated patients indicated increased pain-evoked brain activity in the caudatus nucleus, anterior insula and amygdala after treatment, compared to before treatment; regions implicated in pain inhibitory processes. A 2×2 repeated measures fMRI analysis, comparing milnacipran and placebo, before and after treatment, showed that milnacipran-treated patients had greater pain-evoked activity in the precuneus/posterior cingulate cortex after treatment; a region previously implicated in intrinsic brain function and FM pathology. This finding was only significant when uncorrected for multiple comparisons. The safety analysis revealed that patients from both treatment groups had treatment-emergent adverse events where nausea was the most common complaint, reported by 43.5% of placebo patients and 71.7% of milnacipran-treated patients. Patients on milnacipran were more likely to discontinue treatment because of side effects. ConclusionsOur results provide preliminary indications of increased pain inhibitory responses in milnacipran-treated FM patients, compared to placebo. The psychophysical assessments did not reach statistical significance but reveal a trend toward higher pressure-pain tolerance after treatment with milnacipran, compared to placebo, especially for higher pain intensities. Our fMRI analyses point toward increased activation of the precuneus/posterior cingulum in patients treated with milnacipran, however results were not corrected for multiple comparisons. The precuneus/posterior cingulum is a key region of the default mode network and has previously been associated with abnormal function in FM. Future studies may further explore activity within the default mode network as a potential biomarker for abnormal central pain processing. ImplicationsThe present study provides novel insights for future studies where functional neuroimaging may be used to elucidate the central mechanisms of common pharmacological treatments for chronic pain. Furthermore, our results point toward a potential mechanism for pain normalization in response to milnacipran, involving regions of the default mode network although this finding needs to be replicated in future studies.

Greater dispositional optimism is related to diminished temporal summation of heat pain in older adults with knee pain with and without radiographic evidence of knee osteoarthritis

Existing evidence suggests that personality factors can influence individuals' responses to pain. Of interest, dispositional optimism has been related to diminished pain sensitivity and adaptive pain responses. One explanation for the beneficial contributions of dispositional optimism to the pain experience is that optimism is associated with endogenous pain processing mechanisms. Our group has previously shown that greater dispositional optimism was associated with enhanced endogenous pain-inhibitory processes,1 yet it remains to be tested whether dispositional optimism is also inversely related with pain facilitatory processes such as temporal summation (TS) of pain, a presumed perceptual manifestation of enhanced central excitability.

Testing the relation between dispositional optimism and centrally-mediated pain inhibitory processes: does ethnicity matter?

A preponderance of research to date has focused on risk factors of negative pain-related outcomes and the mechanisms explaining such relations. Far less research has examined variables thought to promote adaptive pain responses and the explanatory processes that may protect individuals from the deleterious effects of pain. Optimism has been shown to beneficially influence a number of health-related factors. Although limited research has suggested an association between optimism and the pain experience, whether optimism is related to pain modulatory processes has not yet been examined.

Ethnicity, Catastrophizing, and Qualities of the Pain Experience

It is generally well established that catastrophizing exerts a potent influence on individuals' experience of pain and accompanying emotional distress. Further, preliminary evidence has shown that meaningful differences among various pain relevant outcomes (e.g., pain ratings, endogenous pain inhibitory processes) can be attributed to individuals' ethnic background. The mechanisms that might explain ethnic differences in pain outcomes are unclear, and it remains to be fully established whether the relation between ethnicity and pain response may be indirectly affected by pain catastrophizing. In the current study, we examined differences in pain responses by ethnicity among healthy, young adults (N=62), and attempted to determine whether such an ethnicity-pain relation was mediated by catastrophizing using the standard Pain Catastrophizing Scale (PCS) and a modified version of the PCS reflecting situational catastrophizing during a cold pressor task. Results showed that pain responses varied by ethnicity, as did reported catastrophizing. Catastrophizing mediated the relation between ethnicity and affective and sensory pain responses. To better explicate our findings, we described the context in which these findings occurred following a "who, what, where, when, and why" approach. This approach provides an efficient description of how our findings align with previous research, while identifying future research that should clarify the theoretical underpinnings of catastrophizing and pain and also inform clinical intervention.