What do plasma beta-endorphin levels reveal about endogenous opioid analgesic function?

Plasma levels of beta-endorphin (BE), an endogenous opioid analgesic, are often reported as they relate to acute and chronic pain outcomes. However, little is known about what resting plasma BE levels might reveal about functioning of the endogenous opioid antinociceptive system. This study directly examined associations between resting plasma BE and subsequent endogenous opioid analgesic responses to acute pain in 39 healthy controls and 37 individuals with chronic low back pain (LBP). Resting baseline levels of plasma BE were assessed. Next, participants received opioid blockade (8 mg naloxone i.v.) or placebo in a double-blind, randomized, crossover design. Participants then underwent two acute pain stimuli: finger pressure (FP) pain and ischaemic (ISC) forearm pain. Blockade effects (naloxone minus placebo pain ratings) were derived to index endogenous opioid analgesic function. In placebo condition analyses for both pain stimuli, higher resting BE levels were associated with subsequently greater reported pain intensity (p's < 0.05), with this effect occurring primarily in healthy controls (BE × Participant Type interactions, p's < 0.05). In blockade effect analyses across both pain tasks, higher resting plasma BE predicted less subsequent endogenous opioid analgesia (smaller blockade effects; p's < 0.05). For the ISC task, these links were significantly more prominent in LBP participants (BE × Participant Type Interactions, p's < 0.05). Results suggest that elevated resting plasma BE may be a potential biomarker for reduced endogenous opioid analgesic capacity, particularly among individuals with chronic pain. Potential clinical implications are discussed.

Cognitive factors influence outcome following multidisciplinary chronic pain treatment: a replication and extension of a cross-lagged panel analysis.

Reducing maladaptive cognitions is hypothesized to constitute an active therapeutic process in multidisciplinary pain programs featuring cognitive-behavioral interventions. A cross-lagged panel design was used to determine whether: a) early-treatment cognitive changes predicted late-treatment pain, interference, activity and mood changes, but not vice versa; b) three cognitive factors made unique contributions to outcome; c) substantial cognitive changes preceded substantial improvements in outcome. Sixty-five chronic pain patients, participating in a 4-week multidisciplinary program, completed measures of pain helplessness, catastrophizing, pain-related anxiety (process factors), pain severity, interference, activity level and depression (outcomes) at pre-, mid- and posttreatment. Results showed that early-treatment reductions in pain helplessness predicted late-treatment decreases in pain and interference, but not vice versa, and that early-treatment reductions in catastrophizing and pain-related anxiety predicted late-treatment improvements in pain severity, but not vice versa. Findings suggested that the three process factors predicted improvements mostly in common. However, little evidence was found that large early-treatment reductions in process variables preceded extensive improvements in pain. Findings replicate those of a recent report regarding cross-lagged effects, and offer support that cognitive changes may indeed influence late-treatment changes in outcomes.

Polyanionic polysaccharides reduce intra-abdominal adhesion and abscess formation in a rat peritonitis model.

BACKGROUND: Intra-abdominal infection is complicated by adhesion and abscess formation. We have assessed the adhesion- and abscess-reducing capacity of various solution volumes and concentrations of two polyanionic polysaccharides, hyaluronan (HA) and carboxymethylcellulose (CMC), in a rat peritonitis model. STUDY DESIGN: In 192 male Wistar rats a bacterial peritonitis was induced using cecal ligation and puncture. After 24 h the abdomen was reopened and the ligated cecum resected. Animals were randomized into three control groups, nine groups treated with various solution volumes (1 to 8 ml) containing different HA concentrations, and four groups treated with 1.7% CMC solution. Rats were killed at day 7, postoperatively, and adhesions were scored at five abdominal sites on a scale from 0 to 4. The presence and size of intra-abdominal abscesses were noted. RESULTS: Fifty-four rats (28%) prematurely died. There was no significant difference in mortality between treatment groups and controls. Treatment with CMC (P < 0.001) and low (0.2 and 0.4%) concentrations of HA (P < 0.005) significantly reduced intra-abdominal adhesion formation. High volumes of 0.2 and 0.4% HA were most effective (P = 0.01). The effect of CMC was volume independent. The incidence of abdominal abscesses was also significantly reduced by treatment with either CMC (P < 0.001) or low concentrations of HA (P < 0.001). With regard to abscess formation the effect was independent of the volume administered for HA, while low volumes of CMC were most effective (P < 0.005). CONCLUSION: Intraperitoneal treatment with either CMC or low-viscosity HA solution reduced intra-abdominal adhesion and abscess formation in a rat peritonitis model. The volume-induced reduction in adhesion formation suggests a hydroflotation effect of HA solution.

A fourth empirically derived cluster of chronic pain patients based on the multidimensional pain inventory: evidence for repression within the dysfunctional group.

The authors proposed that chronic pain patients with repressive defenses are not represented in current 3-cluster solutions of the Multidimensional Pain Inventory (MPI; R. D. Kerns, D. C. Turk, & T. E. Rudy, 1985) and that such a group can be distinguished by using a measure of defensiveness together with subscales of the MPI. They expected these patients to be described both by high defensiveness and by elevated pain and disability but minimal emotional distress. For 178 pain patients, hierarchical cluster analyses were performed on the MPI and Balanced Inventory of Desirable Responding (D. L. Paulhus, 1984). A 3-cluster solution replicated past findings in identifying dysfunctional, interpersonally distressed, and adaptive coper groups. A 4-cluster solution fit the data better, with a repressor group described by high pain, low activity and low distress emerging from the dysfunctional group. Profile analysis of validation measures showed that repressors scored comparably with dysfunctional patients on somatic symptoms of depression, pain severity, and perceived disability but significantly higher on these factors than the adaptive copers. Repressors scored comparably with adaptive copers on cognitive-affective symptoms of depression, anxiety, and anger but significantly lower on these variables than dysfunctional patients. Repressors also reported greater pain severity and perceived disability relative to their reports of negative affect, whereas dysfunctional and adaptive coper groups exhibited no such disparities. Without a measure of defensiveness, the MPI may misclassify a distinct group of patients as dysfunctional, but who readily endorse physical symptoms yet report low levels of emotional distress.

Protection to +12 Gz.

BACKGROUND: The U.S. Air Force has developed +Gz-protective equipment that will provide most pilots protection to +9 Gz with minimal-to-no straining. This equipment includes a pressure breathing system called COMBAT EDGE (CE), which is currently operational, and the Advanced Technology Anti-G Suit (ATAGS), which is not yet operational. For future high-performance aircraft design it is important to know the upper limit of various protective equipment and techniques. METHODS: Six subjects were randomly exposed to a 12-cell matrix composed of +Gz and the following combinations of protective equipment at three seat-back angles (13 degrees, 30 degrees and 55 degrees from the vertical): 1) the standard CSU-13B/P anti-G suit (STD); 2) the STD suit with CE; 3) the ATAGS; and 4) the ATAGS with CE. Relaxed, followed by straining +Gz tolerance was determined using 15-s rapid onset runs to a maximum of +12 Gz. A comprehensive battery of baseline and post-exposure medical surveillance studies was performed to evaluate the medical consequences of these high +Gz exposures. RESULTS: All 6 subjects were able to achieve +12 Gz with various combinations of +Gz-protective equipment, seat-back angle, and various amounts of straining, from none to maximum. When the data were collapsed over all protective equipment there was a significant (p < 0.05) seat effect. Relaxed tolerance to ROR increased with seat-back angle from 13 degrees to 30 degrees to 55 degrees. There was also a significant protective equipment effect when the data were collapsed over all seat-back angles. CONCLUSIONS: These data confirm that effortless protection to +9 Gz is available using ATAGS/CE with the 13 degree and 30 degree seat-back angle (F-15, F-16 and F-22) and to +10.5 Gz with a 55 degree seat-back angle. Moreover, with ATAGS/CE, and a moderate degree of straining, +12 Gz is definitely achievable at 55 degrees, even with reduced anti-G suit pressure at 55 degrees. With additional straining +12 GC is also achievable at the 13 degree and 30 degree seat-back angles.

Evaluation of sepramesh biosurgical composite in a rabbit hernia repair model.

BACKGROUND: In cases such as incisional hernia repair, polypropylene mesh (PPM) can be exposed to the underlying viscera and cause adhesions to the mesh. In this study, a composite prosthesis that was designed to be less susceptible to adhesion formation than PPM was evaluated in a rabbit incisional hernia repair model. MATERIALS AND METHODS: A 5 x 7-cm full-thickness defect was created in the abdominal wall of 30 female New Zealand White rabbits. Ten animals each were repaired with PPM, Bard Composix (PP/ePTFE), or Sepramesh biosurgical composite-a polypropylene mesh coated on one side with chemically modified sodium hyaluronate and carboxymethylcellulose (HA/CMC). The animals were sacrificed after 28 days and the overall performance, including adhesion formation and tissue integration by histology and mechanical testing, was evaluated. RESULTS: In the Sepramesh group, there was a significant reduction in the percentage of surface area covered by adhesions and a significant increase in the percentage of animals with no adhesions compared to standard materials. The tissue integration strength and overall cellular response were similar in all groups. A partially remesothelialized peritoneal surface was often apparent overlying the Sepramesh implant. CONCLUSIONS: Sepramesh biosurgical composite effectively repaired abdominal wall defects in rabbits and reduced adhesion development to the mesh compared to the use of a PPM and a PP/ePTFE composite.

Effects of inertial load and countermeasures on the distribution of pulmonary blood flow.

We assessed the influence of cranial-to-caudal inertial force (+G(z)) and the countermeasures of anti-G suit and positive pressure breathing during G (PBG), specifically during +G(z), on regional pulmonary blood flow distribution. Unanesthetized swine were exposed randomly to 0 G(z) (resting), +3 G(z), +6 G(z), and +9 G(z), with and without anti-G suit and PBG with the use of the Air Force Research Laboratory centrifuge at Brooks Air Force Base (the gravitational force of the Earth, that is, the dorsal-to-ventral inertial force, was present for all runs). Fluorescent microspheres were injected into the pulmonary vasculature as a marker of regional pulmonary blood flow. Lungs were excised, dried, and diced into approximately 2-cm(3) pieces, and the fluorescence of each piece was measured. As +G(z) was increased from 0 to +3 G(z), blood flow shifted from cranial and hilar regions toward caudal and peripheral regions of the lung. This redistribution shifted back toward cranial and hilar regions as anti-G suit inflation pressure increased at +6 and +9 G(z). Perfusion heterogeneity increased with +G(z) stress and decreased at the higher anti-G suit pressures. The distribution of pulmonary blood flow was not affected by PBG. ANOVA indicated anatomic structure as the major determinant of pulmonary blood flow.

Role of transforming growth factor beta-1 in peritonitis-induced adhesions.

Peritonitis is a major cause of intra-abdominal adhesion formation. The overexpression of transforming growth factor beta-1 (TGF-Beta1), a potent mitogen, chemoattractant, and stimulant for collagen synthesis by fibroblasts, has been linked to tissue fibrosis at various sites throughout the body including peritoneal adhesion formation. Hence we hypothesized that the mechanism(s) involved in peritonitis-induced adhesion formation may be mediated through the upregulation of TGF-Beta1 expression. Peritonitis was induced in rats by cecal ligation and puncture, while a control group underwent sham operation. Adhesions were scored and harvested from both groups at 0, 6 and 12 hours and at 1, 2, 4, 7, and 28 days. Tissue expression of TGF-Beta1 mRNA was determined by quantitative reverse transcription-polymerase chain reaction and TGF-Beta1 protein was localized by immunohistochemical analysis. Serum and peritoneal fluid TGF-Beta1 concentrations were quantified by enzyme-linked immunosorbent assay. Compared with sham operation, peritonitis was associated with a significantly greater incidence of abdominal adhesions and a significant increase in the levels of TGF-Beta1 mRNA expression at days 2, 4, and 7. Immunostaining intensity of TGF-Beta1 in adhesions from the peritonitis group also steadily rose through day 7. In peritoneal fluid, the ratio of active:total TGF-Beta1 was significantly increased in the peritonitis group on days 1, 2, and 4 compared with the sham group. These results suggest that peritonitis is associated with the upregulation of TGF-Beta1, a mechanism that may exacerbate adhesion formation.

Repression predicts outcome following multidisciplinary treatment of chronic pain.

This study examined whether repression predicts outcome following multidisciplinary treatment for chronic pain and whether links between anxiety and outcome are obscured by repressors. Ninety-three chronic pain patients completed a 4-week pain program. Lifting capacity, walking endurance, depression, pain severity, and activity were measured at pre- and posttreatment. Low-anxious, repressor, high-anxious, and defensive/high-anxious groups were formed from median splits of Anxiety Content (ACS) and Lie scales of the Minnesota Multiphasic Personality Inventory-2 (MMPI-2; Butcher, Dahlstrom, Graham, Tellegen, & Kaemmer, 1989). Significant ACS x Lie interactions were found for lifting capacity, depression, and pain severity changes. Planned comparisons showed that both repressors and high-anxious patients performed poorly on lifting capacity; repressors alone recovered poorly on depression and pain severity. Results imply that repression may interfere with the process and outcome of pain programs.

Validity of the pain anxiety symptoms scale (PASS): prediction of physical capacity variables.

Anxious responses to pain may lead to avoidance of behavior expected to produce pain. McCracken et al. (1992) developed the Pain Anxiety Symptoms Scale (PASS) to assess anxiety related specifically to pain. Efforts to validate the scale, however, have been confined mostly to examining associations between the PASS and other self-report instruments. This study tested whether PASS scores were related to behavioral performance variables recorded by therapists during a physical capacity evaluation. Participants were 98 male patients with persistent pain referred to two industrial rehabilitation centers. PASS scores were correlated negatively with amount of weight lifted and carried, and results of hierarchical regressions showed that PASS scores accounted for additional variance in these variables when measures of trait anxiety, depression and pain severity were controlled. However, we did not replicate the findings of McCracken et al. (1992) that PASS scores accounted for variance in self-reported disability with trait anxiety, depression or pain severity controlled. Results extend the validity of the PASS and are consistent with models of fear of pain: patients with high PASS scores may avoid potentially painful physical exertion to reduce their fear.

Effect of surgical adhesion reduction devices on the propagation of experimental intra-abdominal infection.

HYPOTHESIS: The use of certain surgical adhesion reduction devices where there is a risk of concomitant bacterial contamination potentiates intra-abdominal infection. DESIGN: Evaluation of adhesion reduction devices in an experimental model of intra-abdominal infection. SETTING: Experimental animal model. INTERVENTIONS: Adhesion reduction devices were administered at the time of bacterial challenge. MAIN OUTCOME MEASURES: Animal mortality rate, abscess formation, and bacterial counts in peritoneal fluid and blood cultures. RESULTS: The use of bioresorbable membrane adhesion reduction devices in the presence or absence of antibiotic therapy did not alter the disease process as compared with appropriate control groups. However, adhesion reduction gels prepared from sodium hyaluronate and carboxymethylcellulose chemically modified with carbodiimide or ferric ion complexed sodium hyaluronate increased the incidence of peritonitis in treated animals. Gel formulations containing diimide-modified carboxymethylcellulose did not have this effect. CONCLUSIONS: The use of certain adhesion reduction devices resulted in the propagation of intra-abdominal infection in an experimental rat model. This outcome was dependent on the composition of the device employed. The use of adhesion reduction devices should be tested in appropriate models of infection where there is the risk of concomitant bacterial contamination.

Repressed anger and patterns of cardiovascular, self-report and behavioral responses: effects of harassment.

We hypothesized that anger repressors would show discrepancies between self-reported anger and cardiovascular and behavioral responses only during harassment. Subjects (N=102) were assigned randomly to condition. In the nonharassment condition, subjects told stories about eight Thematic Apperception Test cards without any harassment. In the harassment condition, subjects told four stories without harassment, and then told four more stories with harassment. Words connoting aggressive behavior and angry/hostile affect were coded from story content. Subjects were classified into low anger expressor, anger repressor, high anger expressor, and defensive anger expressor categories based on median splits of the Anger-Out Subscale and Marlowe-Crowne Social Desirability Scale. Results showed that harassed anger repressors reported anger comparable to that of low anger expressors but less than high expressors, whereas their heart rate (HR) reactivity was comparable to high expressors, but greater than low anger expressors. Increases in anger words did not distinguish repressors from other groups. Repressed anger may represent a distinct anger management style characterized by a discrepancy between acknowledged anger and cardiovascular reactivity--effects that become fully manifest only during interpersonal provocation.

Relationships among patient hostility, anger expression, depression, and the working alliance in a work hardening program.

Hostility, anger expression, and depression may adversely affect the response of chronic pain patients to pain or functional restoration programs by hampering the development of good working alliances between patients and physical or occupational therapists. Measures of hostility, anger expression, and depression and the Working Alliance Inventory (WAI) were completed by 71 patients with chronic pain (stemming from work-related injuries) prior to starting a "work hardening" program. The physical or occupational therapist acting as any given patient's "program manager" completed the WAI, as well. Hostility and anger expression were correlated negatively only with patient ratings of the working alliance. Therapist ratings were predicted by the interaction of patient anger expression and depression, such that therapists reported their poorest alliances with patients who were both depressed and expressed anger. Results imply that hostility and the propensity to express anger may diminish a pain patient's capacity to foster a collaborative relationship with physical or occupational therapists, while therapists may readily become alienated from depressed and irritable patients.

Anger management style and the prediction of treatment outcome among male and female chronic pain patients.

Anger is a prominent emotion experienced by chronic pain patients. Anecdotes suggest that anger predicts poor outcome following multidisciplinary pain programs, but no empirical evidence documents this link. We expected that patient anger expression or suppression would predict poor outcome following a pain program and that gender differences would emerge. Pre- to posttreatment measures of lifting capacity, walking endurance, depression, pain severity and activity level were collected from 101 chronic pain patients. An 'anger expression x gender' interaction was found such that anger expression among males was correlated negatively with lifting capacity improvements. 'Anger suppression x gender' interactions emerged such that anger suppression among males was correlated negatively with improvements in depression and general activities. These effects remained significant after controlling for trait anger. Thus, how anger is managed may exert unique influence on outcomes apart from the effects of mere anger proneness, at least among male pain patients.

Pulmonary blood flow redistribution by increased gravitational force.

This study was undertaken to assess the influence of gravity on the distribution of pulmonary blood flow (PBF) using increased inertial force as a perturbation. PBF was studied in unanesthetized swine exposed to -Gx (dorsal-to-ventral direction, prone position), where G is the magnitude of the force of gravity at the surface of the Earth, on the Armstrong Laboratory Centrifuge at Brooks Air Force Base. PBF was measured using 15-micron fluorescent microspheres, a method with markedly enhanced spatial resolution. Each animal was exposed randomly to -1, -2, and -3 Gx. Pulmonary vascular pressures, cardiac output, heart rate, arterial blood gases, and PBF distribution were measured at each G level. Heterogeneity of PBF distribution as measured by the coefficient of variation of PBF distribution increased from 0.38 +/- 0.05 to 0.55 +/- 0.11 to 0.72 +/- 0.16 at -1, -2, and -3 Gx, respectively. At -1 Gx, PBF was greatest in the ventral and cranial and lowest in the dorsal and caudal regions of the lung. With increased -Gx, this gradient was augmented in both directions. Extrapolation of these values to 0 G predicts a slight dorsal (nondependent) region dominance of PBF and a coefficient of variation of 0.22 in microgravity. Analysis of variance revealed that a fixed component (vascular structure) accounted for 81% and nonstructure components (including gravity) accounted for the remaining 19% of the PBF variance across the entire experiment (all 3 gravitational levels). The results are inconsistent with the predictions of the zone model.

Cognitive and physical capacity process variables predict long-term outcome after treatment of chronic pain.

Cognitive-behavioral and physical therapies are incorporated into multidisciplinary chronic pain programs because changes in pain cognitions and physical capacity may represent therapeutic processes that facilitate favorable outcome. Decreases in depression, however, may explain treatment responses more parsimoniously. Measures of pain helplessness, lifting capacity, walking endurance, depression, pain severity, and activity level were collected from 94 chronic pain patients at pre- and posttreatment and at 3- to 6-month follow-up evaluations. Decreases in pain helplessness were linked to pain severity reduction, whereas walking endurance increases were related to improvements in activity levels and downtime even after controlling for effects of depression decreases. Thus, cognitive and physical capacity changes that occur through pain treatment may make unique contributions to long-term outcome.

Reduction of postsurgical adhesion formation in the rabbit uterine horn model with use of hyaluronate/carboxymethylcellulose gel.

OBJECTIVE: To assess the efficacy of a bioabsorbable gel for reducing primary postoperative adhesions. DESIGN: A randomized, prospective, blinded study. SETTING: Academic research environment. ANIMALS: Forty-one New Zealand Rabbits. INTERVENTION(S): A chemically modified hyaluronate and carboxymethylcellulose (HA/CMC) gel formulation was applied to a bilateral uterine horn injury. Postoperative adhesions were assessed at a second-look laparoscopy. MAIN OUTCOME MEASURE(S): The uterine horn model was shown to be adhesiogenic, with 29 (70%) of 42 untreated uterine horns found to have adhesions. After gel treatment, 22 (55%) of 40 uterine horns were free of adhesions compared with 12 (30%) of 42 controls. RESULT(S): Animals treated with HA/CMC gel had significantly reduced postsurgical adhesion scores when compared with controls. CONCLUSION(S): Treatment of injured uterine horn with HA/CMC gel resulted in a significant reduction in postoperative surgical adhesions.

Altered cardiovascular/pain regulatory relationships in chronic pain.

In healthy individuals, there is an inverse relationship between resting blood pressure (BP) and pain sensitivity. This study examined possible dysregulation of this adaptive relation in chronic pain patients, and tested whether the extent of this dysregulation is a function of pain duration. Continuous resting BP's were assessed for 5 min after a 5-min rest period in 121 chronic benign pain patients. Unlike the inverse relationship observed previously in normals, mean resting diastolic. BPs during the assessment period were correlated positively with ratings of pain severity. A Pain Duration x Systolic BP interaction emerged (p < .05) such that the magnitude of the BP-pain relation was greatest in patients with the longest duration of pain, r(38) = .50, p < .001. A hypothesized progressive alteration in endogenous pain regulatory systems in chronic pain patients was supported. A possible role of endogenous opioid dysfunction in accounting for these alterations is discussed.

Linking symptom-specific physiological reactivity to pain severity in chronic low back pain patients: a test of mediation and moderation models.

Symptom-specific reactivity to stress (lower paraspinal muscle reactivity) among chronic low back pain (CLBP) patients may exacerbate chronic pain. It was hypothesized that among CLBP patients (N = 107) only stress-induced lower paraspinal reactivity, and not reactivity in other indexes, would predict pain severity (PS), and that lower paraspinal reactivity would mediate or moderate links between depression and PS. Electromyogram readings from lower paraspinal and trapezius muscles, systolic and diastolic blood pressures, and heart rate were collected during mental arithmetic (MA) and an anger recall interview. The moderator hypothesis was supported: Only lower paraspinal reactivity during MA was related significantly to PS, but only among patients with high levels of depression. Thus, a profile of lower paraspinal hyperreactivity plus depressed affect may aggravate CLBP.