Hyperalgesia after a Drinking Episode in Young Adult Binge Drinkers: A Cross-Sectional Study.

AIMS: Rodent studies propose potential mechanisms linking excessive drinking and pain hypersensitivity (hyperalgesia), such that stress hormones (i.e. epinephrine and cortisol) mediate induction and maintenance of alcohol withdrawal-induced hyperalgesia. The first aim of this study was to examine whether hyperalgesia would occur within 48 h after a drinking episode in healthy young adult binge drinkers. The second was to examine whether stress hormones and negative effect would be associated with binge drinking or alcohol withdrawal-associated hyperalgesia. METHODS: A cross-sectional experiment was conducted in five groups with naturally occurring drinking (mean age = 19.6, range 18-29 years): abstainers (n = 43, 54% female), moderate drinkers with (n = 50, 50% female) or without recent drinking (i.e. within 48 h, n = 23, 26% female) and binge drinkers with (n = 36, 58% female) or without recent drinking (n = 25, 44% female). All types of drinkers endorsed drinking about 2-3 times a month and 2-3 years of drinking history. RESULTS: Muscle pressure pain thresholds were significantly lower in the binge group with recent drinking compared to other groups, but cutaneous mechanical and heat pain thresholds were not significantly different across the five groups. Basal epinephrine levels were significantly higher in binge groups regardless of recent drinking, but cortisol and negative effect were not significantly different across the five groups. CONCLUSIONS: This is the first study to show that alcohol withdrawal-associated muscle hyperalgesia may occur in healthy episodic binge drinkers with only 2-3 years of drinking history, and epinephrine may play a role in binge drinking-associated hyperalgesia.

Divergent effects of conditioned pain modulation on subjective pain and nociceptive-related brain activity.

BACKGROUND AND OBJECTIVES: Pain is a complex experience involving both nociceptive and affective-cognitive mechanisms. The present study evaluated whether modulation of pain perception, employing a conditioned pain modulation (CPM) paradigm, is paralleled by changes in contact heat-evoked potentials (CHEPs), a brain response to nociceptive stimuli. METHODS: Participants were 25 healthy, pain-free, college students (12 males, 13 females, mean age 19.24 ± 0.97 years). Twenty computer-controlled heat stimuli were delivered to the non-dominant forearm and CHEPs were recorded at Cz using a 32-channel EEG system. After each stimulus, participants rated the intensity of the heat pain using the 0-100 numerical rating scale. The latency and amplitude of N2, P2 components as well as single-sweep spectral analysis of individual CHEPs were measured offline. For CPM, participants had to submerge their dominant foot into a neutral (32 °C) or noxious (0 °C) water bath. CHEPs and heat pain ratings were recorded in 3 different conditions: without CPM, after neutral CPM (32 °C) and after noxious CPM (0 °C). RESULTS: The noxious CPM induced a facilitatory pain response (p = 0.001) with an increase in heat pain following noxious CPM compared to neutral CPM (p = 0.001) and no CPM (p = 0.001). Changes in CHEPs did not differ between conditions when measured as N2-P2 peak-to-peak amplitude (p = 0.33) but the CPM significantly suppressed the CHEPs-related delta power (p = 0.03). Changes in heat pain in the noxious CPM were predicted by trait catastrophizing variables (p = 0.04). CONCLUSION: The current study revealed that pain facilitatory CPM is related to suppression of CHEPs delta power which could be related to dissociation between brain responses to noxious heat and pain perception.

Cumulative Childhood Adversity as a Risk Factor for Common Chronic Pain Conditions in Young Adults.

OBJECTIVE: Multiple and specific types of childhood adverse events are risk factors for chronic pain conditions. Although both can covary, no study has evaluated one aspect while controlling for the other. Therefore, the current study examined whether more adverse events would be a risk factor for common chronic pain conditions and pain medication use in young adults after controlling for different adversity types such as physical, emotional, and sexual traumatic events or vice versa. METHODS: This cross-sectional study recruited 3,073 undergraduates (72% female, mean age = 18.8 years, SD = 1.4 years) who completed the survey for current health status and early life traumatic events. RESULTS: More adverse events were associated with a 1.2-1.3-fold increase in the odds of any chronic pain, chronic back pain, headache, and dysmenorrhea with adjusting for adversity types, but they were not associated with the risk of comorbid pain conditions and use of pain medications. In contrast, specific adversity types were unrelated to chronic pain conditions when controlling for the number of adverse events. CONCLUSIONS: Cumulative childhood adverse events may be a more relevant risk factor for chronic pain conditions than the experience of a specific type of adverse event. Clinicians and researchers need to evaluate cumulative childhood adversity when assessing its link to chronic pain.

Childhood Adversity and Pain Facilitation.

OBJECTIVE: This study investigated whether childhood adversity would be associated with hypersensitivity on two measures of central pain facilitation: area of secondary allodynia and temporal summation of second pain (TSSP), and whether pain facilitation would be explained by adult posttraumatic stress disorder (PTSD) symptoms. METHOD: Participants endorsing high (n = 31) and low (n = 31) childhood adversity underwent capsaicin-induced secondary allodynia and TSSP testing. The tests were conducted a week apart with test order counterbalanced. RESULTS: Larger areas of secondary allodynia were observed in the high adversity group compared with the low adversity group (F(1,60) = 4.81, p = .032). This group difference was largely (62%) explained by greater PTSD symptoms in the high adversity group. Although no overall difference was found in TSSP slopes (p = .886), this was attributed to an order by group interaction (F(1,58) = 5.07, p = .028) and low power. Subsequent analyses revealed positive TSSP slopes in the high adversity group when TSSP testing was performed first, and this order effect was associated with blunted sympathetic responses to TSSP on the first visit. The two facilitation measures were unrelated (p = .631). CONCLUSIONS: Larger areas of secondary allodynia were observed in the high adversity group, which was explained largely by PTSD symptoms. This suggests that adversity-related changes in pain facilitation may underlie the association between childhood adversity and generalized widespread pain. Although TSSP was affected by previous testing, adversity-related pain facilitation was observed when TSSP testing occurred first. Finally, adversity was not associated with a consistent pattern of hypersensitivity across the two measures of central pain facilitation.

Generalized Pain Sensitization and Endogenous Oxytocin in Individuals With Symptoms of Migraine: A Cross-Sectional Study.

OBJECTIVE: The current study examined pain and neurogenic inflammation responses to topical capsaicin during the interictal period (between headache) and their relationship with plasma oxytocin in individuals with migraine. BACKGROUND: Individuals with migraine can experience generalized (extracephalic) hyperalgesia, which can persist even between headache attacks. Elevated levels of plasma and cerebrospinal fluid oxytocin have been observed during migraine attacks, oxytocin levels being positively associated with the intensity of migraine symptoms. However, whether oxytocin plays a role in the mechanisms of generalized pain sensitization and neurogenic inflammation during the interictal period has not been studied yet. Understanding migraineurs' interictal pain phenotype and endogenous oxytocin might help identify individuals who would benefit from intranasal oxytocin treatment. METHODS: Thirty-two subjects with migraine and 26 healthy controls underwent pain testing. The current study compared capsaicin-induced pain, central sensitization (areas of secondary mechanical allodynia and hyperalgesia), and neurogenic inflammation (capsaicin-induced flare) responses on the nondominant volar forearm between migraineurs and healthy controls. Additionally, we studied plasma oxytocin levels and their relationship to migraine symptoms, experimental pain and affect. RESULTS: The results indicated a significant group effect (P = .019): Migraineurs reported greater capsaicin-induced pain unpleasantness (M = 1.2, SD = 1.4) on a 0-10 scale and showed larger areas of flare (LnM = 2.8, SD = 0.4) than healthy controls (M = 0.5, SD = 0.8; LnM = 2.6, SD = 0.4; ps < .032). In a subgroup analysis, enhanced capsaicin-induced pain unpleasantness was found in the chronic (P = .007), but not the episodic (Ps > .200), migraineurs. The oxytocin levels were elevated in migraineurs and accounted for 18% of the group difference in capsaicin-induced pain unpleasantness. Within migraineurs, interictal oxytocin levels were negatively associated with psychological distress (Ps < .030). However, during the interictal period, pain sensitivity in extracephalic regions and plasma oxytocin levels were unrelated to migraine symptom parameters (Ps > .074). Lastly, the results found no group difference in areas of secondary mechanical allodynia and hyperalgesia (Ps >.298). CONCLUSION: The current study revealed that individuals with migraine exhibit enhanced extracephalic capsaicin-induced pain unpleasantness and flare responses during interictal periods. In addition, migraineurs, especially those with chronic migraine, had slightly elevated interictal oxytocin levels compared to controls, which was associated with their affective component of experimental pain. Therefore, treatment targeting affective pain during the interictal period may help to reduce generalized pain in migraine. Furthermore, endogenous increases in oxytocin may be a compensatory mechanism that may help decrease affective distress in migraineurs. The therapeutic effects of intranasal oxytocin may benefit migraineurs by reducing their affective distress.

Molecular and preclinical basis to inhibit PGE2 receptors EP2 and EP4 as a novel nonsteroidal therapy for endometriosis.

Endometriosis is a debilitating, estrogen-dependent, progesterone-resistant, inflammatory gynecological disease of reproductive age women. Two major clinical symptoms of endometriosis are chronic intolerable pelvic pain and subfertility or infertility, which profoundly affect the quality of life in women. Current hormonal therapies to induce a hypoestrogenic state are unsuccessful because of undesirable side effects, reproductive health concerns, and failure to prevent recurrence of disease. There is a fundamental need to identify nonestrogen or nonsteroidal targets for the treatment of endometriosis. Peritoneal fluid concentrations of prostaglandin E2 (PGE2) are higher in women with endometriosis, and this increased PGE2 plays important role in survival and growth of endometriosis lesions. The objective of the present study was to determine the effects of pharmacological inhibition of PGE2 receptors, EP2 and EP4, on molecular and cellular aspects of the pathogenesis of endometriosis and associated clinical symptoms. Using human fluorescent endometriotic cell lines and chimeric mouse model as preclinical testing platform, our results, to our knowledge for the first time, indicate that selective inhibition of EP2/EP4: (i) decreases growth and survival of endometriosis lesions; (ii) decreases angiogenesis and innervation of endometriosis lesions; (iii) suppresses proinflammatory state of dorsal root ganglia neurons to decrease pelvic pain; (iv) decreases proinflammatory, estrogen-dominant, and progesterone-resistant molecular environment of the endometrium and endometriosis lesions; and (v) restores endometrial functional receptivity through multiple mechanisms. Our novel findings provide a molecular and preclinical basis to formulate long-term nonestrogen or nonsteroidal therapy for endometriosis.

Association Between Borderline Personality Features and Temporal Summation of Second Pain: A Cross-Sectional Study.

Individuals with greater borderline personality features may be vulnerable to chronic pain. Because pain is an unpleasant sensory and emotional experience, affect dysregulation as the core personality feature may be linked to pain hypersensitivity. Studies have found that greater borderline features are associated with increased intensity in clinical and experimental pain, and that depression mediates this increase. The current study further examined the association between borderline features and heat pain sensitivity, the contribution of affect dysregulation and the other borderline personality factors (identity problems, negative relationships, self-harming/impulsivity) to the association, and depression as a mediator. Additionally, we examined whether blunted sympathetic responses mediate the association between borderline features and temporal summation of second pain (TSSP). Thermal pain threshold, thermal TSSP and aftersensations pain were assessed in 79 healthy individuals with varying degrees of borderline features. TSSP is a proxy measure for central sensitization and refers to the gradual increase in pain to repeated nociceptive stimuli. A regression analysis showed that greater borderline features predicted greater TSSP (ß = .22, p = .050, R2 = .05). Borderline features were unrelated to pain threshold and TSSP decay. A stepwise regression showed greater TSSP in individuals with greater borderline features was accounted for by the negative relationships factor rather than the affect dysregulation factor. The results of mediational analyses showed depression and blunted sympathetic skin conductance responses mediated the positive association between TSSP and borderline features.

Childhood Adversity and Pain Sensitization.

OBJECTIVE: Childhood adversity is a vulnerability factor for chronic pain. However, the underlying pain mechanisms influenced by childhood adversity remain unknown. The aim of the current study was to evaluate the impact of childhood adversity on dynamic pain sensitivity in young adults. METHODS: After screening for childhood adverse events and health status, healthy individuals reporting low (below median; n = 75) or high levels of adversity (the top 5%; n = 51) were invited for pain testing. Both groups underwent heat pain threshold and temporal summation of second pain (TSSP) testing after reporting depressive symptoms. TSSP refers to a progressive increase in pain intensity with repetition of identical noxious stimuli and is attributed to central sensitization. Changes in pain ratings over time (slope) were computed for TSSP sensitization and decay of subsequent aftersensations. RESULTS: The high-adversity group showed greater TSSP sensitization (meanslope, 0.75; SDpositive slope, 1.78), and a trend toward a slower decay (meanslope, -11.9; SD, 3.4), whereas the low-adversity group showed minimal sensitization (meanslope, 0.07; SDnear-zero slope, 1.77), F(1,123) = 5.84, p = .017 and faster decay (meanslope, -13.1; SD, 3.4), F(1,123) = 3.79, p = .054. This group difference remained significant even after adjusting for adult depressive symptoms (p = .033). No group difference was found in heat pain threshold (p = .85). Lastly, the high-adversity group showed blunted cardiac and skin conductance responses. CONCLUSIONS: These findings suggest that enhancement of central sensitization may provide a mechanism underlying the pain hypersensitivity and chronicity linked to childhood adversity.

Enhanced Area of Secondary Hyperalgesia in Women with Multiple Stressful Life Events: A Pilot Study.

OBJECTIVE: Stressful life events are associated with increased pain severity and chronicity. However, the mechanism underlying this association remains disputed. Recent animal studies suggest that chronic stress increases pain sensitivity and persistence by enhancing peripheral and central sensitization mechanisms. To test this hypothesis in humans, the authors examined whether sensitization is enhanced in healthy women reporting more stressful life events using the topical capsaicin test. METHODS: Thirty-two healthy young women reporting varying levels of stressful life events were invited for laboratory pain testing. Capsaicin was applied topically to the volar forearm. Measurements included capsaicin-induced spontaneous pain and area of secondary hyperalgesia in the region surrounding capsaicin application. Physiological (heart rate and skin conductance) and self-reported affective (emotional valence and arousal) states were also measured. RESULTS: The results indicate that more stressful life events predicted a linear increase in the area of secondary hyperalgesia (ß = 0.40, p = 0.023, R2 = 0.16), but not the intensity of secondary hyperalgesia nor capsaicin-induced spontaneous pain. These findings suggest that life stressors may be associated with heightened central sensitization manifested by an increased area of secondary hyperalgesia. Additionally, life stressors were related to greater sympathetic cardiac, but not to affective responses to capsaicin-induced pain. CONCLUSION: This study shows that women reporting more stressful life events show a larger area of secondary mechanical hyperalgesia. These preliminary findings suggest that life stressors may facilitate pain processing by enhancing central sensitization.

Effect of written emotional disclosure on secondary hyperalgesia in women with trauma history.

OBJECTIVE: This study investigated the effects of written emotional disclosure on a model of chronic pain in healthy women with and without trauma history. METHOD: Participants were prescreened for their trauma history (N = 78) and randomized to a disclosure or a control writing condition. Pain testing occurred either 1 day or 1 month after disclosure. Capsaicin was applied to the forearm to evoke spontaneous burning pain at the application site and mechanical secondary hyperalgesia in the surrounding untreated skin. RESULTS: As hypothesized, the effect of disclosure on the area and intensity of secondary hyperalgesia depended on trauma history and time of testing (F(1,69) ≥ 7.37, p = .008). Disclosure increased secondary hyperalgesia in participants with trauma history compared with those without trauma when testing occurred 1 day after writing (F(1,69) ≥ 5.27, p ≤ .025), whereas the opposite pattern was observed 1 month later (F(1,69) ≥ 4.88, p ≤ .031). Of the participants with trauma history in the disclosure condition, secondary hyperalgesia was reduced at 1 month compared with 1 day after writing (p = .001). Moreover, greater use of positive emotional words predicted reduced secondary hyperalgesia at 1 month (ß = -0.71, p = .022). In contrast, disclosure had no effect on spontaneous pain. CONCLUSIONS: Disclosure modulates secondary hyperalgesia observed in women with trauma history, producing a short-term enhancement and a long-term reduction. This suggests that disclosure has a long-term protective effect that reduces sensitization of pain, which may explain the therapeutic effects of disclosure in patients with chronic pain.

Emotion regulation strategies moderate the impact of negative affect induction on alcohol craving in college drinkers: an experimental paradigm.

Objectives: Observational studies suggest emotion regulation (ER) as a potential treatment target for problematic college drinking. The primary aim of this laboratory study was to determine whether trait ER strategies would moderate the impact of negative affect induction on alcohol craving in college drinkers. Methods: Participants were randomly assigned to a neutral (n = 74) or a negative affect induction (n = 76) and reported their craving after the affect inductions. Results: Greater use of drinking to cope and less use of cognitive reappraisal predicted greater alcohol craving after the negative affect induction, but not after the neutral condition. In contrast, emotion suppression did not predict alcohol craving in either condition. Conclusion: Our results highlight the role of ER tendencies-particularly the benefits of cognitive reappraisal-on alcohol craving when experiencing emotional distress. Therefore, ER strategies may be an important target for college drinkers to prevent and reduce problematic drinking.

Traumatic Life Experience and Pain Sensitization: Meta-analysis of Laboratory Findings.

OBJECTIVES: Psychological trauma often co-occurs with pain. This relationship has been explored using laboratory pain measures; however, findings have been mixed. Previous studies have limited operationalization of trauma (eg, posttraumatic stress disorder) or pain (eg, pain thresholds), which may contribute to conflicting results. Further, prior reviews likely underrepresent trauma experiences among people who are not receiving clinical care, limiting generalizability. MATERIALS AND METHODS: We systematically reviewed the existing literature on the relationship between psychological trauma (eg, car accidents, sexual assault, childhood abuse, neglect) and laboratory pain (ie, quantitative sensory testing measures of pain threshold, intensity, summation, modulation), using inclusive criteria. The direction of the relationship between psychological trauma and pain sensitivity was evaluated, and moderation by purported pain mechanism (ie, pain detection, suprathreshold pain, central sensitization, inhibition) was explored. RESULTS: Analyses were conducted using 48 studies that provided 147 effect sizes. A multivariate random-effects model with robust variance estimation resulted in a small but statistically significant overall effect size of g=0.24 (P=0.0002), reflecting a positive association between psychological trauma and enhanced laboratory pain sensitivity. Upon examination of mechanistic moderators, this relationship appears driven by effects on pain detection (g=0.28, P=0.002) and central sensitization (g=0.22, P=0.04). While effect sizes were similar across all moderators, effects on suprathreshold pain and inhibition were not statistically significant. DISCUSSION: Findings demonstrate an overall pattern of trauma-related pain enhancement and point to central sensitization as a key underlying mechanism.

Restraint stress fails to render C57BL/6 mice susceptible to Theiler's virus-induced demyelination.

OBJECTIVES: Multiple sclerosis is a degenerative disease of the CNS with a pathology consistent with immunological mediation. Although its cause is unknown, multiple factors are thought to influence both the onset and exacerbation of the disease, including both genetic background as well as environmental factors. METHODS: We are interested in the effect of psychological stress on the onset and exacerbation of Theiler's virus-induced demyelinating disease (TVID), a murine model of MS in which viral persistence facilitates demyelination. In the current study, we determined whether chronic restraint stress (RS)-induced immunosuppression could result in the establishment of a persistent CNS infection in the normally TVID-resistant C57BL/6 mouse strain, resulting in demyelination. RESULTS: Our data indicated that RS repeated over the course of 7 days was not sufficient to cause decreases in virus-specific adaptive immunity, and did not significantly alter CNS viral levels. Furthermore, chronic repeated RS lasting until 4 weeks after infection altered neither the development of virus-specific IgG nor motor function determined by Rotarod analysis. In addition, histological analysis of the CNS of stressed mice indicated no inflammation or demyelination on day 193 after infection. CONCLUSION: These results suggest that stress alone is not sufficient to overcome genetic resistance to TVID in the C57BL/6 mouse strain.

Effects of stress on the immune response to Theiler's virus--implications for virus-induced autoimmunity.

Psychological stress is an important factor in susceptibility to many diseases. Our laboratory has been investigating the impact of stress on the susceptibility to Theiler's virus-induced demyelination (TVID), a mouse model of multiple sclerosis. Using immunodominant viral peptides specific for identification of either CD4(+) or CD8(+) T cells, stress reduced IFN-gamma-producing virus-specific CD4(+) and CD8(+) T cells in the spleen and CD8(+) T cells in the CNS. Expression of mRNA for the Th1 transcription factor T-bet and the Th2 transcription factor GATA-3 were decreased in spleen cells isolated from stressed mice. Cytokine production by cells isolated from the CNS or spleens following stimulation with virus indicated that stress decreased both type 1 and type 2 responses. The adverse effects of stress were partially reversed by concurrent RU486 administration but mimicked by dexamethasone, indicating a major role for glucocorticoids. Global stress-induced immunosuppression resulted in higher levels of virus replication and dissemination. The higher viral load subsequently led to an earlier disease onset and more severe clinical and histological signs of demyelinating disease. Our results have important implications for understanding the pathogenesis of MS, and suggest that stressful events during early infection with an agent capable of inducing demyelination may result in immunosuppression and failure to eliminate the pathogen, which in turn may lead to the development of MS.

Greater mechanical temporal summation of pain in Latinx-Americans and the role of adverse life experiences.

INTRODUCTION: Adverse life experiences disproportionately impact Latinx-Americans and are related to greater chronic pain rates. However, little is known about how adversities interact with central pain mechanisms for the development of later pain among Latinx-Americans. OBJECTIVES: The current study examined the relationship between adverse life experiences (eg, trauma and ethnic discrimination) and correlates (eg, social status) with mechanical temporal summation of pain (a proxy measure of central sensitization) between pain-free U.S. native Latinx (n = 65) and non-Hispanic White (NHW) (n = 51) adults. METHODS: Participants completed self-report adverse life experience and correlational measures regarding childhood and adulthood and a mechanical temporal summation protocol. RESULTS: Relative to NHWs, Latinx-Americans reported experiencing significantly greater trauma, discrimination, and lower social status during childhood and adulthood, along with greater temporal summation. Contrary to hypotheses, recent and lifetime experiences of ethnic discrimination significantly correlated with less temporal summation among Latinx-Americans. Decreases in objective and subjective social status across the lifespan (childhood to present day) correlated with greater temporal summation for Latinx-Americans. However, r-to-z transformation analyses confirmed that significant adversity and social status correlations observed among the Latinx group did not significantly differ from NHW participants. CONCLUSIONS: The present findings highlight the complex association between adverse experiences, adverse experience risk factors, and pain for Latinx-Americans. Given the disproportion of experienced pain and adversity among Latinx-Americans, the current findings suggest that a better understanding of the unique adversities for this sample may help elucidate the mechanisms underlying the relationship between adversities, adversity correlates, and pain risk for Latinx-Americans.

Spinal glia modulate both adaptive and pathological processes.

Recent research indicates that glial cells control complex functions within the nervous system. For example, it has been shown that glial cells contribute to the development of pathological pain, the process of long-term potentiation, and the formation of memories. These data suggest that glial cell activation exerts both adaptive and pathological effects within the CNS. To extend this line of work, the present study investigated the role of glia in spinal learning and spinal learning deficits using the spinal instrumental learning paradigm. In this paradigm rats are transected at the second thoracic vertebra (T2) and given shock to one hind limb whenever the limb is extended (controllable shock). Over time these subjects exhibit an increase in flexion duration that reduces net shock exposure. However, when spinalized rats are exposed to uncontrollable shock or inflammatory stimuli prior to testing with controllable shock, they exhibit a learning deficit. To examine the role of glial in this paradigm, spinal glial cells were pharmacologically inhibited through the use of fluorocitrate. Our results indicate that glia are involved in the acquisition, but not maintenance, of spinal learning. Furthermore, the data indicate that glial cells are involved in the development of both shock and inflammation-induced learning deficits. These findings are consistent with prior research indicating that glial cells are involved in both adaptive and pathological processes within the spinal cord.

Restraint stress modulates virus specific adaptive immunity during acute Theiler's virus infection.

Multiple sclerosis (MS) is a devastating CNS disease of unknown origin. Multiple factors including genetic background, infection, and psychological stress affect the onset or progression of MS. Theiler's murine encephalomyelitis virus (TMEV) infection is an animal model of MS in which aberrant immunity leads to viral persistence and subsequently results in demyelination that resembles MS. Here, we examined how stress during acute TMEV infection altered virus-specific cell mediated responses. Using immunodominant viral peptides specific for either CD4(+) or CD8(+) T cells, we found that stress reduced IFN-gamma producing virus-specific CD4(+) and CD8(+) T cells in the spleen and CD8(+) T cells CNS. Cytokine production by cells isolated from the CNS or spleens following stimulation with virus or viral peptides, indicated that stress decreased both type 1 and type 2 responses. Glucocorticoids were implicated in the decreased T cell function as the effects of stress were partially reversed by concurrent RU486 administration but mimicked by dexamethasone. As T cells mediate viral clearance in this model, our data support the hypothesis that stress-induced immunosuppression may provide a mechanism for enhanced viral persistence within the CNS.

Glucocorticoid exposure alters the pathogenesis of Theiler's murine encephalomyelitis virus during acute infection.

Previous research has shown that chronic restraint stress exacerbates Theiler's virus infection, a murine model for CNS inflammation and multiple sclerosis. The current set of experiments was designed to evaluate the potential role of glucocorticoids in the deleterious effects of restraint stress on acute CNS inflammatory disease. Exposure to chronic restraint stress resulted in elevated levels of corticosterone as well as increased clinical scores and weight loss (Experiment 1). In addition, corticosterone administration alone exacerbated behavioral signs of TMEV-induced sickness (i.e. decreased body weight, increased symptoms of encephalitis, and increased mortality) and reduced inflammation in the CNS (Experiment 2). Infected subjects receiving exogenous corticosterone showed exacerbation of acute phase measures of sickness and severe mortality as well as decreased viral clearance from CNS (Experiment 3). These findings indicate that corticosterone exposure alone is sufficient to exacerbate acute CNS inflammatory disease.

Predicting the completion of an integrative and intensive outpatient chronic pain treatment with the personality assessment inventory.

The effects of intensive, integrative treatments for chronic pain are affected by patient compliance, and in many cases, selecting noncompliant individuals adversely impacts the cost-effectiveness of such programs. The pretreatment identification of individuals who are at risk for dropout could assist clinicians in augmenting treatments with motivational enhancement strategies for high-risk patients or using such information to select individuals who are most likely to complete a given intervention program. In this study, we tested the ability of indicators from the Personality Assessment Inventory (PAI; Morey, 1991), administered prior to treatment, to identify individuals who dropped out of a 20-day chronic pain program. Results replicate findings from outpatient psychotherapy research in finding that PAI Mean Clinical Elevation and Treatment Process Index significantly differentiated dropouts from graduates, particularly when the Treatment Rejection scale suggested patients were motivated for treatment. We discuss these results and offer recommendations for the prediction of treatment dropout in pain settings.

Optimal scoring of the Multidimensional Pain Inventory in a chronic pain sample.

The Multidimensional Pain Inventory (MPI) is one of the most commonly used self-report instruments in pain settings. The MPI can be used to classify patients into three clusters or its nine scales can be treated as dimensions in efforts to understand patient heterogeneity. Previous research suggests the existence of a fourth cluster, whose members have been labeled 'repressors,' that emerges with the addition of a defensiveness scale to the MPI. The current paper compared the abilities of MPI cluster and dimensional models with and without a measure of defensiveness to capture variability in validating variables related to personality, psychopathology, physical functioning, and treatment outcome in a chronic pain sample. Results suggest that dimensional models consistently outperform cluster models in explaining variance in outcome variables, and that the addition of a measure of defensiveness increments the validity offered by the MPI scales. Implications for the assessment of pain patients are discussed.