Student suggestions for addressing heavy episodic drinking.

Objective This study examines student suggestions for other students, campuses, and society to address heavy episodic drinking (HED) and associated harms. Participants: Included 110 post-secondary students (27 males, 83 females), ages 17 to 30 years, from five universities across four Canadian provinces. Method: Purposeful sampling was used to screen in participants who drank in excess of Canada's Low-Risk Alcohol Drinking Guidelines. As part of a larger study, focus groups were held with qualifying students examining HED behaviors, suggestions and potential barriers to addressing HED among post-secondary students. Results: Suggestions included providing earlier education on harms, receiving messages from respected peers and adults, and teaching how to drink in moderation. Barriers included peer pressure, not knowing own limits, and post-secondary drinking culture. Conclusions: Campuses might not be using the most effective methods to reduce HED, may be facing unknown barriers, and need to understand perspectives of students in order to reduce HED.

A meta-analysis of problem gambling risk factors in the general adult population.

BACKGROUND AND AIMS: Few meta-analyses have been conducted to pool the most constant risk factors for problem gambling. The present meta-analysis summarizes effect sizes of the most frequently assessed problem gambling risk factors, ranks them according to effect size strength and identifies any differences in effects across genders. METHOD: A random-effects meta-analysis was conducted on jurisdiction-wide gambling prevalence surveys on the general adult population published until March 2019. One hundred and four studies were eligible for meta-analysis. The number of participants varied depending on the risk factor analyzed, and ranged from 5327 to 273 946 (52% female). Weighted mean odds ratios were calculated for 57 risk factors (socio-demographic, psychosocial, gambling activity and substance use correlates), allowing them to be ranked from largest to smallest with regard to their association with problem gambling. RESULTS: The highest odds ratio (OR) was for internet gambling [OR = 7.59, 95% confidence interval (CI) = 5.24, 10.99, P < 0.000] and the lowest was for employment status (OR = 1.03, 95% CI = 0.87, 1.22, P = 0.718). The largest effect sizes were generally in the gambling activity category and the smallest were in the socio-demographic category. No differences were found across genders for age-associated risk. CONCLUSIONS: A meta-analysis of 104 studies of gambling prevalence indicated that the most frequently assessed problem gambling risk factors with the highest effect sizes are associated with continuous-play format gambling products.

Gambling Self-Control Strategies: A Qualitative Analysis.

There is limited research exploring the perceptions of people who gamble on the self-control strategies used to limit their gambling. This qualitative study examines self-control strategies used to limit money spent gambling, frequency of gambling, and time spent gambling. A total of 56 people who gamble (27 males and 29 females) participated in nine focus groups and five individual interviews in Montreal, Calgary, and Toronto (Canada). Self-control strategies used to limit their gambling expenditure were more common than frequency or time limiting strategies. Strategies to limit expenditure included: restricting access to money; keeping track of money allocated to gambling activities; and avoiding certain types of gambling activities. Various contextual factors were identified to influence those strategies, including social influences; winning or losing; using substances. Findings from this study emphasize the importance of communicating clear gambling limits to people who gamble, as well as the value of developing individual self-control strategies to limit frequency, time and money spent gambling.

Use of Self-control Strategies for Managing Gambling Habits Leads to Less Harm in Regular Gamblers.

There is little research on the control strategies used by the general public to self-manage gambling habits and avoid harmful consequences. The current study sought to identify the most common self-control strategies of people who gamble regularly, the characteristics of those who use them, and assess the effectiveness of limit-setting strategies in reducing gambling-related harm. We recruited a large sample (N = 10,054) of Canadian adults who reported gambling activity in the past 12 months. Participants completed a survey that assessed gambling habits, use of control strategies including quantitative limit setting, and gambling related harm. The most common control strategies were setting predetermined spending limits, tracking money spent, and limiting alcohol consumption. The number of self-control strategies used by gamblers was positively associated with gambling involvement, annual income, problem gambling severity and playing electronic gaming machines. Approximately 45% of respondents failed to adhere to self-determined quantitative limits for spending, frequency, and time spent gambling. People who stayed within their gambling limits were less likely to report harm even after controlling for other risk factors. However, the effectiveness of remaining within one's personal spending limit decreased for those whose limits exceed $200CAN monthly. The findings support public health interventions that promote lower-risk gambling guidelines aimed at helping gamblers stay within spending, frequency and duration limits.

Childhood autism spectrum disorders and exposure to nitrogen dioxide, and particulate matter air pollution: A review and meta-analysis.

BACKGROUND AND OBJECTIVE: Genetic and environmental factors have been recognized to play an important role in autism. The possibility that exposure to outdoor air pollution increases the risk of autism spectrum disorder (ASD) has been an emerging area of research. Herein, we present a systematic review, and meta-analysis of published epidemiological studies that have investigated these associations. METHODS: We undertook a comprehensive search strategy to identify studies that investigated outdoor air pollution and autism in children. Overall, seven cohorts and five case-control studies met our inclusion criteria for the meta-analysis. We summarized the associations between exposure to air pollution and ASD based on the following critical exposure windows: (i) first, second and third trimester of pregnancy, (ii) entire pregnancy, and (iii) postnatal period. Random effects meta-analysis modeling was undertaken to derive pooled risk estimates for these exposures across the studies. RESULTS: The meta-estimates for the change in ASD associated with a 10µg/m3 increase in exposure in PM2.5 and 10 ppb increase in NO2 during pregnancy were 1.34 (95% CI:0.83, 2.17) and 1.05 (95% CI:0.99, 1.11), respectively. Stronger associations were observed for exposures received after birth, but these estimates were unstable as they were based on only two studies. O3 exposure was weakly associated with ASD during the third trimester of pregnancy and during the entire pregnancy, however, these estimates were also based on only two studies. CONCLUSION: Our meta-analysis support the hypothesis that exposure to ambient air pollution is associated with an increased risk of autism. Our findings should be interpreted cautiously due to relatively small number of studies, and several studies were unable to control for other key risk factors.

[Use of rapid diagnostic tests of tonsillitis in medical practice. Survey conducted from November 2006 to January 2007 in Pays de la Loire (France)]. / Utilisation des tests de diagnostic rapide de l'angine en médecine générale. Enquête réalisée de novembre 2006 à janvier 2007 dans les Pays de la Loire.

INTRODUCTION: The use of the rapid diagnostic test (RDT) and the strategy of management of pharyngitis in medical practice are little known. METHODS: During the 2006-2007 winter, a survey was conducted in the Pays de la Loire Region to evaluate the use of the RDT. A focus group was also organised. RESULTS: Data were collected from 525 patients (patients who were consulting for a sore throat, angina or patients for whom a RDT was made). RDT were performed on 245 patients (46%). The sixty positive RDT patients systematically received an antibiotic. Twenty negative RDT patients received an antibiotic. More than 75% of GPs considered the RDT useful or very useful. DISCUSSION: The guidelines for the management of pharyngitis are known but they are partially followed by physicians. Many countries have national guidelines for the management of tonsillitis and they are also not unanimous. When patients had pharyngitis symptoms, the frequency of antibiotic prescription was lower when the RDT was used as recommended by the French Medicines Agency (AFSSAPS). The treatment must be short in order to improve the compliance of outpatients and reduce the inappropriate use of antibiotics. CONCLUSION: A decrease in antibiotics prescription was recorded in the community. It was attributed to the availability of the RDT provided by the CNAMTS (French National Health Service). Moreover, the RDT are still free for practitioners and their reimbursement could be extended to hospital.

Obestatin partially affects ghrelin stimulation of food intake and growth hormone secretion in rodents.

Administration of ghrelin, an endogenous ligand for the GH secretagogue receptor 1a (GHSR 1a), induces potent stimulating effects on GH secretion and food intake. However, more than 7 yr after its discovery, the role of endogenous ghrelin remains elusive. Recently, a second peptide, obestatin, also generated from proteolytic cleavage of preproghrelin has been identified. This peptide inhibits food intake and gastrointestinal motility but does not modify in vitro GH release from pituitary cells. In this study, we have reinvestigated obestatin functions by measuring plasma ghrelin and obestatin levels in a period of spontaneous feeding in ad libitum-fed and 24-h fasted mice. Whereas fasting resulted in elevated ghrelin levels, obestatin levels were significantly reduced. Exogenous obestatin per se did not modify food intake in fasted and fed mice. However, it inhibited ghrelin orexigenic effect that were evident in fed mice only. The effects of obestatin on GH secretion were monitored in superfused pituitary explants and in freely moving rats. Obestatin was only effective in vivo to inhibit ghrelin stimulation of GH levels. Finally, the relationship between octanoylated ghrelin, obestatin, and GH secretions was evaluated by iterative blood sampling every 20 min during 6 h in freely moving adult male rats. The half-life of exogenous obestatin (10 microg iv) in plasma was about 22 min. Plasma obestatin levels exhibited an ultradian pulsatility with a frequency slightly lower than octanoylated ghrelin and GH. Ghrelin and obestatin levels were not strictly correlated. In conclusion, these results show that obestatin, like ghrelin, is secreted in a pulsatile manner and that in some conditions; obestatin can modulate exogenous ghrelin action. It remains to be determined whether obestatin modulates endogenous ghrelin actions.

Cellular localization of apelin and its receptor in the anterior pituitary: evidence for a direct stimulatory action of apelin on ACTH release.

Apelin is a bioactive peptide recently identified as the endogenous ligand of the human orphan G protein-coupled receptor APJ. The presence of apelin-immunoreactive nerve fibers, together with the detection of apelin receptor mRNA in the parvocellular part of the paraventricular nucleus and the stimulatory action of apelin on corticotropin-releasing hormone release, indicate that apelin modulates adrenocorticotropin (ACTH) release via an indirect action on the hypothalamus. However, a direct action of apelin in the anterior pituitary cannot be excluded. Here, we provided evidence for the existence of an apelinergic system within the adult male rat pituitary gland. Double immunofluorescence staining indicated that apelin is highly coexpressed in the anterior pituitary, mainly in corticotrophs (96.5 +/- 0.3%) and to a much lower extent in somatotropes (3.2 +/- 0.2%). Using in situ hybridization combined with immunohistochemistry, a high expression of apelin receptor mRNA was also found in corticotrophs, suggesting a local interaction between apelin and ACTH. In an ex vivo perifusion system of anterior pituitaries, apelin 17 (K17F, 10(-6) M) significantly increased basal ACTH release by 41%, whereas apelin 10 (R10F, 10(-6) M), an inactive apelin fragment, was ineffective. In addition, K17F but not R10F induced a dose-dependent increase in K(+)-evoked ACTH release, with maximal increase being observed for a 10(-6) M concentration. Taken together, these data outline the potential role of apelin as an autocrine/paracrine-acting peptide on ACTH release and provide morphological and neuroendocrine basis for further studies that explore the physiological role of apelin in the regulation of anterior pituitary functions.

[Ghrelin: a striking example of neuroendocrine peptide pleiotropy]. / La ghréline, un exemple saisissant de pléïotropie des peptides neuroendocriniens.

Ghrelin, a peptide predominantly produced by the stomach, has been discovered as a natural ligand of the growth hormone secretagogue receptor (GHS-R) type 1a. Shortly there after, it attracted enormous interest since it appeared as the first peripheral orexigenic factor. Besides, ghrelin exerts other neuroendocrine metabolic and non-endocrine actions (e.g. cardiovascular activities) that may rely on the widespread distribution of ghrelin and its receptor (GHS-R). The existence of several GHS-R subtypes and evidences that neuroendocrine and metabolic but not all other ghrelin actions are dependent on acylation on serine 3 add further complexity to the system whose major physiological role remains to be definitely elucidated. Ghrelin knockout(-/-) mice are neither anorectic nor dwarf though GHS-R-/- are slightly underweight and do not respond to ghrelin with increased GH secretion or appetite. Thus, the continuation of the fascinating ghrelin story as well as its potential pathophysiological implications in endocrinology and internal medicine remain open avenues for future investigations.

The role of the small bowel in the regulation of circulating ghrelin levels and food intake in the obese Zucker rat.

Circulating levels of ghrelin, a stomach peptide that promotes food intake, rise before and fall after meal. We aimed to investigate whether there is an independent contribution of the small bowel to the regulation of ghrelin and appetite. A duodenal-jejunal bypass (DJB) with preservation of normal gastric volume and exposure to nutrients was performed in 12-wk-old obese Zucker ZDF fa/fa rat. Food intake, weight gain, 48-h fasting, and 24-h refeeding levels of total and acylated ghrelin were measured. The DJB was challenged against gastric banding (GB), diet, and a sham operation in matched animals. Normal controls were age-matched Wistar rats, which underwent either DJB or a sham operation. The Zucker obese animals showed a paradoxical increase of acylated ghrelin levels after refeeding (+30% with respect to fasting levels; P = 0.001), an abnormality that was completely reversed only by the DJB (-30%; P = 0.01) but not after GB, diet, or sham operation. In obese rats, the DJB resulted in significantly less food intake and weight gain compared with both GB (P < 0.05) and sham operation (P < 0.01). In sharp contrast, the DJB did not alter food intake and weight gain in normal rats. The DJB does not physically restrict the flow of food but restores meal-induced suppression of acylated ghrelin and significantly reduces food intake in Zucker obese rats. These findings suggest an independent intestinal contribution to the regulation of the dynamic ghrelin response to eating and the possibility that defective signaling from the proximal bowel could be involved in the pathogenesis of obesity/hyperphagia.

Novel analogs of ghrelin: physiological and clinical implications.

Ghrelin, the 28 amino acid peptide recently identified as the natural ligand for the growth hormone (GH) secretagogue (GHS) receptor, has multiple activities in addition to stimulation of GH secretion, including stimulation of feeding and weight gain. To utilize these actions for potential therapeutic benefit, we have produced analogs of human ghrelin with enhanced metabolic stability, affinity for the GHS receptor, and efficacy in stimulating weight gain. We have also discovered an analog of ghrelin, BIM-28163, that is an antagonist at the GHS receptor and that fully inhibits GHS receptor activation induced by native ghrelin. In vivo, BIM-28163 does not increase GH secretion but fully blocks ghrelin-induced GH secretion. In contrast, BIM-28163 acts as a full agonist with regard to the ghrelin actions of stimulating weight gain and food intake. These results suggest that a receptor other than the GHS receptor mediates the actions of ghrelin on feeding and weight gain. This concept is strengthened by our observation that at certain hypothalamic sites, BIM-28163 acts as an antagonist of ghrelin-induced neuronal activation, while at other sites, both ghrelin and BIM-28163 induce neuronal activation via the same receptor. Collectively, these results indicate the existence of a novel ghrelin receptor that may regulate the feeding activity of ghrelin. Using BIM-28163 as a tool to define the endogenous role of ghrelin in normal GH secretion, we have demonstrated that antagonism of the GHS receptor in normal rats does not impair the pulsatility of GH secretion but lowers the pulse amplitude and mean GH level. These results demonstrate that endogenous ghrelin acts to amplify the basic pattern of GH secretion established by the interplay of hypothalamic GH-releasing hormone and somatostatin. These studies demonstrate the feasibility of creating ghrelin analogs that are selective for specific activities, as well as their utility in dissecting the role of ghrelin in both normal physiology and specific pathologies.

Delayed age-associated decrease in growth hormone pulsatile secretion and increased orexigenic peptide expression in the Lou C/JaLL rat.

Since modifications in the growth hormone/insulin-like growth factor 1 (GH/IGF-1) axis and/or caloric restriction are involved in the ageing process, GH secretory profiles, total IGF-1, ghrelin, and leptin plasma levels and expression of genes implicated in somatotrope axis and food intake regulation in hypothalamus and pituitary were compared in 3-, 12-, and 24-month-old male Lou C/Jall rats and their parent strain, the Wistar rats. The Lou C/Jall strain may appear as a healthy ageing model, since it does not become obese with age and maintains its caloric intake at 2 years of age. The GH pulsatile secretion decreased from 3 months in Wistar, but only after 12 months in Lou C/Jall rats. The IGF-1 levels were lower in Lou C/Jall rats and decreased more steeply with ageing as compared with Wistar rats. The total ghrelin levels were higher in young Lou C/Jall rats than in Wistar rats, but increased similarly with age in both strains. The leptin concentrations increased with ageing only in Wistar rats. By semiquantitative reverse-transcription polymerase chain reaction, pituitary GH secretagogue receptors and GH mRNA levels were more abundant in Lou C/Jall rats, and the latter decreased with ageing in Wistar rats only. Hypothalamic growth-hormone-releasing hormone and GH secretagogue receptor mRNA levels were similar in both strains and transiently increased only in middle-aged Wistar rats. Agouti-related peptide, neuropeptide Y, and orexin mRNA levels were more abundant in the Lou C/Jall rat hypothalamus, and the two former tended to further increase with age only in this strain. Conversely, the hypothalamic pro-opiomelanocortin mRNA levels were higher in old Wistar rats. In conclusion, ageing in Lou C/Jall rats is associated with a delayed decrease in pulsatile GH secretion in the presence of a lower IGF-1 tone and an increase in the expression of orexigenic neuropeptides in the hypothalamus.

Balance in ghrelin and leptin plasma levels in anorexia nervosa patients and constitutionally thin women.

Ghrelin, a 28-amino acid octanoylated peptide, has recently been identified in rat stomach as an endogenous ligand for the GH secretagogue receptor. In addition to GH-releasing properties, exogenous ghrelin injections exert orexigenic effects in both rodents and humans. As the endogenous peptide appears directly related to feeding behavior, we assessed its plasma levels in anorexia nervosa (AN) patients before and after renutrition and in constitutionally thin subjects with body mass indexes (BMIs) equivalent to those of AN women but with no abnormal feeding behavior. The relationships between plasma ghrelin levels and other neuroendocrine and nutritional parameters, such as GH, leptin, T3, and cortisol, were also investigated. In AN patients, morning fasting plasma ghrelin levels were doubled compared with levels in controls, constitutionally thin subjects, and AN patients after renutrition. Twenty-four-hour plasma ghrelin, GH, and cortisol levels determined every 4 h were significantly increased, whereas 24-h plasma leptin levels were decreased in AN patients compared with controls and constitutionally thin subjects. Both plasma ghrelin and leptin levels returned to control values in AN patients after renutrition. Constitutionally thin subjects displayed intermediate 24-h plasma ghrelin and leptin levels, significantly different from controls and AN patients, whereas GH and cortisol were not modified. Ghrelin was negatively correlated with BMI, leptin, and T(3) in controls, constitutionally thin subjects, and AN patients, whereas no correlation was found between GH and ghrelin or between cortisol and ghrelin. Ghrelin and BMI or T3 were still correlated after renutrition, suggesting that ghrelin is also a good nutritional indicator. Basal and GHRH-stimulated GH release were significantly increased in AN patients only. In conclusion, ghrelin is increased in AN and constitutionally thin subjects who display very low BMI but different eating behaviors, suggesting that not only is ghrelin dependent on body fat mass, but it is also influenced by nutritional status. Even though endogenous ghrelin is not strictly correlated with basal GH secretion, it may be involved in the magnitude of GHRH-induced GH release in AN patients.

Functional alteration of the somatotrophic axis in transgenic mice with liver-specific expression of human insulin-like growth factor binding protein-1.

In earlier work, postnatal growth restriction (more marked in males) was observed in a model of transgenic mice with liver-specific expression of human IGF binding protein-1. This was associated with diminished plasma IGF-I levels, the cause of which remained unexplained. Subsequently, abnormalities of CNS development were ascertained, justifying investigation of the somatotrophic axis. Pituitary gland weight in transgenic animals was reduced proportionally to body weight. Immunohistochemical examination of the pituitaries in 3- to 4-mo-old mice revealed somatotrophs of normal size in homozygotes, but density was decreased to approximately two thirds of that in wild-type siblings (p = 0.001). The same was true of lactotrophs. The GH content of the pituitary was significantly reduced in heterozygotes (p < 0.02) and more so in homozygotes (p < 0.0003), although the GH/total protein ratio was similar to that in wild types. Pituitary perifusion experiments showed that in vitro the amounts of GH secreted under basal conditions and under GH-releasing hormone stimulation were similar in transgenic and wild-type mice. Ten days of treatment with human GH (100 microg/d) in 45-d-old transgenic and wild-type mice provoked significant weight gain (p = 0.02) in all animals, the means being 12.4% for homozygotes and 10.4% in heterozygotes, as opposed to 5.8% in wild-type mice. The increase in weight tended to correlate with an increase in plasma IGF-I. From these results, we conclude that the reduced plasma IGF-I in IGF binding protein-1 transgenic mice may result from insufficient GH production by the depressed number of somatotrophs, possibly associated with functional alteration of hypothalamic control.

Inhibitory control of growth hormone secretion by somatostatin in rat pituitary GC cells: sst(2) but not sst(1) receptors are coupled to inhibition of single-cell intracellular free calcium concentrations.

Rat pituitary tumor cells (GC cells) exhibit spontaneous oscillations of intracellular free calcium concentration ([Ca(2+)](i)) that allow continuous release of growth hormone (GH). Of the somatostatin (SRIH) receptor subtypes (sst receptors) mediating SRIH action, sst(1) and sst(2) receptors are highly expressed by GC cell membranes. In the present study, the effects of sst(1) or sst(2) receptor activation on single-cell [Ca(2+)](i) were investigated in GC cells by confocal fluorescence microscopy. In addition, the effects of sst(1) or sst(2) receptor activation on GH secretion were also studied. Our results demonstrate that SRIH decreases [Ca(2+)](i) baseline and almost completely blocks Ca(2+) transients through activation of sst(2) but not of sst(1) receptors. In contrast, SRIH effectively inhibits GH secretion through activation of both sst(1) and sst(2) receptors. Blocking Ca(2+) transients is less efficient than SRIH to inhibit GH release. The cyclic octapeptide, CYN-154806, antagonizes sst(2) receptors at [Ca(2+)](i) since it abolishes the sst(2) receptor-mediated inhibition of [Ca(2+)](i) without affecting single-cell Ca(2+) signals. On the other hand, CYN-154806 alone potently inhibits GH secretion through the involvement of pertussis toxin-sensitive G proteins. In conclusion, the present results demonstrate that SRIH inhibition of GH release in GC cells involves mechanisms either dependent or independent on SRIH modulation of [Ca(2+)](i). The implications of CYN-154806 inhibition of GH secretion are discussed.

Ultradian rhythmicity of ghrelin secretion in relation with GH, feeding behavior, and sleep-wake patterns in rats.

Ghrelin, an endogenous ligand for the GHS receptor, stimulates GH secretion and gastrointestinal motility and has orexigenic effects. In this study, the relationships between ghrelin, GH secretion, feeding behavior, and sleep-wake patterns were investigated in adult male rats. The half-life of exogenous ghrelin (10 microg i.v.) in plasma was about 30 min. Repeated administration of ghrelin at 3- to 4-h intervals (one during lights-on and two during lights-off periods) increased GH release and feeding activity, and decreased rapid eye movement sleep duration. Endogenous plasma ghrelin levels exhibited pulsatile variations that were smaller and less regular compared with those of GH. No significant correlation between GH and ghrelin circulating levels was found, although mean interpeak intervals and pulse frequencies were close for the two hormones. In contrast, ghrelin pulse variations were correlated with food intake episodes in the lights off period, and plasma ghrelin concentrations decreased by 26% in the 20 min following the end of the food intake periods. A positive correlation between ghrelin levels and active wake was found during the first 3 h of the dark period only. In conclusion, ghrelin, in addition to affecting GH secretion, gastrointestinal motility, and feeding activity, also modifies sleep-wake patterns. However, a direct action of ghrelin per se or the indirect effects of feeding (and all of its attendant metabolic sequelae) on sleep cannot be differentiated. Moreover, ghrelin secretion is pulsatile and directly related to feeding behavior only.

Chronic pain induces a paradoxical increase in growth hormone secretion without affecting other hormones related to acute stress in the rat.

In several diseases chronic pain is associated with long-lasting pathophysiological responses which differ strongly from those observed in acute situations. When persisting, acute pain often results in physical and psychological stress which may in turn aggravate the initial pathological state. In the present work we examined the secretory patterns of pituitary hormones related to acute stress (growth hormone (GH), prolactin (PRL) and beta-endorphin (beta-END)) in rats during the phase of Freund adjuvant-induced arthritis (AIA, a model used for chronic pain studies) when chronic pain is maximum (14 and 21 days, postinoculation (PI)). Using radio-immunoassay hormones were measured in plasma samples taken every 30 min for 7 h in free-moving rats 14 and 21 days after Freund adjuvant or vehicle injection and in control animals. The total amount of GH secretion was higher at 14 and 21 days PI in AIA rats as compared to vehicle-treated and control animals, and the pulsatility of GH secretory pattern was not modified by AIA. PRL and beta-END secretion were not significantly different in arthritic rats as compared to controls. These results show that GH, PRL and beta-END responses induced by acute stress are not observed during the AIA phase when chronic pain is maximum. Thus, in our experimental conditions, beta-END and PRL do not seem to be good plasma markers of chronic pain.(ABSTRACT TRUNCATED AT 250 WORDS)