- Research article
- Open Access
- Open Peer Review
Factors explaining variance in perceived pain in women with fibromyalgia
BMC Musculoskeletal Disordersvolume 3, Article number: 12 (2002)
We hypothesized that a substantial proportion of the subjectively experienced variance in pain in fibromyalgia patients would be explained by psychological factors alone, but that a combined model, including neuroendocrine and autonomic factors, would give the most parsimonious explanation of variance in pain.
Psychometric assessment included McGill Pain Questionnaire, General Health Questionnaire, Hospital Anxiety and Depression Rating Scale, Eysenck personality Inventory, Neuroticism and Lie subscales, Toronto Alexithymia Scale, and Multidimensional Health Locus of Control Scale and was performed in 42 female patients with fibromyalgia and 48 female age matched random sample population controls. A subgroup of the original sample (22 fibromyalgia patients and 13 controls) underwent a pharmacological challenge test with buspirone to assess autonomic and adrenocortical reactivity to serotonergic challenge.
Although fibromyalgia patients scored high on neuroticism, anxiety, depression and general distress, only a minor part of variance in pain was explained by psychological factors alone. High pain score was associated with high neuroticism, low baseline cortisol level and small drop in systolic blood pressure after buspirone challenge test. This model explained 41.5% of total pain in fibromyalgia patients. In population controls, psychological factors alone were significant predictors for variance in pain.
Fibromyalgia patients may have reduced reactivity in the central sympathetic system or perturbations in the sympathetic-parasympathetic balance. This study shows that a biopsychosocial model, including psychological factors as well as factors related to perturbations of the autonomic nervous system and hypothalamic-pituitary-adrenal axis, is needed to explain perceived pain in fibromyalgia patients.
Fibromyalgia is a chronic pain syndrome with steadily fluctuating musculo-skeletal pain as the main symptom. However, despite intensive research, the primary mechanisms underlying the etiopathogenesis of fibromyalgia remain elusive.
Some psychiatric studies suggest a relationship to anxiety disorder in a significant subgroup [1, 2], while other studies have found that fibromyalgia is highly associated with depressive disorders [3–7]. Many psychometric studies indicate an association between fibromyalgia, chronic distress, anxiety, depression and certain personality traits [8–15], although conflicting results exist [16, 17].
During the last decade many authors have suggested that perturbations in the autonomic nervous system is a key element in the fibromyalgia syndrome, however, contradictory results have been reported [18–23]. Also perturbations of the hypothalamic-pituitary-adrenal (HPA) axis, leading to relative insufficiency of the adrenal glands and hypocortisolism, is a neuroendocrine finding that has been described in fibromyalgia patients [24–26].
Stress, either physical, emotional or metabolic in nature, may be the essential underlying factor leading to psychiatric and somatic symptoms in fibromyalgia patients through a final common pathway . The physiology of stress includes CNS and peripheral components, involving the hypothalamic-pituitary-adrenal (HPA) axis, the hypothalamic-pituitary-gonadal (HPG) axis and the autonomic (sympathetic) system.[28, 29]. Stress, leading to perturbations in all these systems, may elicit pain in fibromyalgia patients .
Although a vast literature concerning etiopathogenetic factors in the fibromyalgia syndrome exists, we have found no published studies focusing upon which of all these factors that are most important to explain the ever changing and troublesome pain in these patients. This is a clinical important and meaningful question, as knowledge about factors influencing variance in pain is essential in the search for more efficacious pain treatment for fibromyalgia patients. To clarify this question, we assessed pain, psychiatric symptoms and personality factors in patients with fibromyalgia and population based controls. We also used a psychopharmacological challenge test to assess autonomic and adrenocortical cortisol responsiveness. We hypothesized that a substantial proportion of the subjectively experienced variance in pain in fibromyalgia patients would be explained by psychological factors alone, but that a combined model also including neuroendocrine and autonomic factors as a base of the symptomatology would give the most likely explanation of variance in pain.
Materials and methods
Caucasian female fibromyalgia patients fulfilling the ACR diagnostic criteria for fibromyalgia  were randomly selected from the Outpatient clinic of the Rheumatological department, Haukeland University Hospital. Forty-two female patients with mean age 44 years (range 29–63) were included.
The control group was population-based and consisted of age-matched Caucasian women living in the city of Bergen recruited from the National Register by a randomised computer procedure. Mean age for the 48 controls was 46 years (range 23–68).
All subjects not using any psychoactive, anti-inflammatory or antihistaminic drugs on daily basis who were included sample I, were invited to take part in the further study. Twenty-two women with fibromyalgia (mean age 45 years, range 29–63), and 14 female controls (mean age 43 years, range 30–65) accepted and were included.
All subjects underwent a detailed and comprehensive clinical physical examination with registration of demographic and general medical data. No significant group differences were found in age or total family monthly income. Fibromyalgia patients had on average 11 years of education, while control subjects had 13 years (p= 0.018).
Pain was assessed by the Norwegian version of the MPQ . The Norwegian version has three main scales: sensoric pain, affective pain and evaluative pain. Sensoric pain is defined as the sum score of 12 subscales on different sensoric aspects of pain. Affective pain is the sum score of the 5 word groups describing affective aspects of pain. One word group gives the score for evaluative pain. Total pain is the sum score of sensoric, affective and evaluative pain. One fibromyalgia patient and one control did not complete the questionnaire.
The patients filled in a package of questionnaires. General Health Questionnaire 30-item version (GHQ-30) assesses the presence of distress and overall well-being . Sum score was calculated by the Likert method (0-1-2-3). Hospital Anxiety and Depression scale (HAD-A and HAD-D) is constructed to measure psychological (psychic) symptoms of anxiety and depression in a medically ill population .
The neuroticism scale of the Eysenck Personality Questionnaire (EPQ-N) assesses general tendency to over-responsiveness or over-reactivity (neuroticism) . The typical high EPQ-N scorer is an anxious, worrying individual, moody and frequently depressed. She is likely to sleep badly, and to suffer from various psychosomatic disorders. High EPQ-N-scores have been reported among patients with fibromyalgia. The lie scale of the Eysenck Personality Questionnaire (EPQ-L) assesses a tendency towards social conformity and a tendency to give only the answers the person supposes are "correct". Very high scores may be associated with actual lying.
Alexithymia was measured by the 26-item version of Toronto Alexithymia Scale (TAS) . Alexithymia is a multidimensional construct defined by a difficulty in identifying and describing feelings, a difficulty in distinguishing between feelings and bodily sensations, a paucity of fantasies and a preoccupation with external events. Alexithymia has been proposed to increase the risk for functional syndromes.
Multi Dimensional Health Locus of Control Scale (MHLCS) is an ordinal scale with three subscales of 6 items each (scoring 0–6). MHLCS measures how the subjects evaluated the possibility to have control of their own health . The Internal control score is a measure of the individuals' own perceived control of their health. Chance score measures a tendency to perceive health as an outcome of luck or fate. External control score is a measure of the individuals' tendency to expect outcome to be directed by powerful others. In general terms, internal locus of control has been found to predict better coping.
Buspirone challenge test
A buspirone challenge test was performed to assess autonomic and adrenocortical responsiveness in the subjects. Buspirone is a well-known and safe azapiron, which produces a fall in blood pressure. This effect is at least partly due to inhibition of sympathoexcitatory neurons located in the rostral ventrolateral medulla . However, buspirone may also decreases blood pressure through mechanisms associated with parasympathetic activation).). In addition, buspirone induces plasma adrenocorticotropic hormone (ACTH) and cortisol release .
All the premenopausal women were tested within the first two weeks of the menstrual cycle, i.e. in the follicular phase. Buspirone tests began at 8.30 a.m. after an overnight fast. A venous cannula was inserted, and after 15 minutes rest a blood sample was taken for baseline determinations of plasma cortisol. At 9 a.m. 60 mg of oral buspirone in special pharmacy-prepared gelatine-containing capsules was administered. Blood pressure and venous samples were drawn after 60, 90, and 150 minutes. The time points were selected after a review of the literature which showed these time points to be the most adequate for measurement of blood pressure and hormonal responses to buspirone [41–43]. The subjects rested semi-supine throughout the blood-sampling period and were not allowed to sleep.
Venous samples were taken into tubes and centrifuged within 4 hours. Plasma was stored at -80°C until assay.
The statistical analyses were conducted by the SPSS-PC statistical package, version 9.0 (SPSS 1999). Mean differences in variables were assessed by one-way analyses of variance. Correlation analyses were performed between pain variables and psychological and variables derived from the buspirone challenge test. Linear regression analyses with stepwise backward procedures were performed to find the model giving the most parsimonious explanation of the variance in pain. In the large sample, all psychological variables were entered into the regression analysis. Psychological factors that contributed significantly to explained variance in pain in fibromyalgia patients, were entered together with buspirone challenge test variables in the regression analysis from the limited sample.
All subjects were thoroughly informed by personal instruction and a written informed consent was obtained at inclusion. The Regional ethics committee and The Norwegian Data Inspectorate accepted the study. The study was performed in accordance with the Helsinki declaration.
As expected, fibromyalgia patients had higher scores than controls on all pain scales (Table 1). Scores for sensoric, affective and evaluative pain were significantly inter-correlated in both groups with correlation coefficients between 0.41 and 0.91.
Fibromyalgia patients scored higher than controls on anxiety (HAD-A), depression (HAD-D), general distress (GHQ-30) and neuroticism (EPQ-N). The MHLCS factor "Chance" was higher, and "Internal" was lower in the patient group than in the control group (Table 2).
As expected, psychological symptom scores on HAD-A, HAD-D and GHQ were highly inter-correlated (r > 0.60, p < 0.001) and correlated also highly (r > 0.50, p < 0.01) with EPQ-N and alexithymia (TAS) scores in both groups.
In fibromyalgia patients, sensoric, affective and total pain correlated significantly with EPQ-N (r = 0.31 - 0.34, p = 0.03 - 0.05), and affective pain correlated significantly with TAS (r = 0.32, p = 0.04). In controls, sensoric, affective and total pain scores correlated positively with HAD-A (r = 0.30, p = 0.03), HAD-D (r = 0.44, p = 0.002), GHQ (r = 0.46, p = 0.001), EPQ-N (r = 0.40, p = 0.004) and negatively with MHLCS "Internal"(r = -0.45, p = 0.002).
No significant group differences were seen in baseline cortisol level or in baseline systolic or diastolic blood pressure. Buspirone produced a significant time-dependent increase in plasma cortisol and a significant fall in systolic and diastolic blood pressure with no significant group differences. In fibromyalgia patients, high pain scores (sensoric, affective and total) were significantly correlated with low baseline cortisol (Table 3). A consistent pattern of negative correlations between pain scores and cortisol response to buspirone was also seen. These correlations did not reach statistical significance however (rmax = - 0.37, p = 0.09). Pain scores were also significantly correlated with drop in systolic and diastolic blood pressure (high pain, low drop in blood pressure, Table 3). In controls, affective pain score was significantly correlated (r = -0.56, p = 0.04) with drop in systolic, but not diastolic, blood pressure after buspirone. However, on the contrary to what was found in fibromyalgia patients, high affective pain score was associated with a large drop in systolic blood pressure.
Predictors of pain
In the total sample, only a small proportion of variance in pain could be explained by variables related to personality and psychological symptoms in the 42 fibromyalgia patients. The best model consisted of the variables EPQ-N and EPQ-L, which explained 0% of the variance in evaluative pain, 12.6% of variance in affective pain, 13.5% of variance in sensoric pain and 15.7% of variance in total pain.
A larger proportion of variance in pain was explained by psychological variables in the 48 control subjects. A model consisting of the variables Internal and Chance health locus of control and total GHQ score explained 21.6% of variance in evaluative pain, 32.6% of variance in affective pain, 28.0% of variance in sensoric pain and 32.5% of variance in total pain.
In the subjects who also performed the buspirone test, a model consisting of EPQ-N, baseline cortisol level and change in systolic blood pressure explained 41.5% of total pain in fibromyalgia patients. High pain score was associated with high EPQ-N, low baseline cortisol level and small drop in systolic blood pressure after buspirone challenge test (Table 4). In controls, EPQ-N was the only significant predictor for variance in sensoric- and total pain.
The main finding in this study is that a biopsychosocial model including psychological factors as well as factors related to perturbation of the autonomic nervous system and the HPA-axis explained a substantial part of variance of pain in the fibromyalgia patients.
When only personality factors and psychological distress was taken into account, we found a more limited impact of personality factors and psychological distress on pain severity than what has been reported in some previous studies [8, 9, 44, 45]. A possible explanation for this could be that our fibromyalgia group consisted of extreme cases with high scores on psychopathology and pain with small inter-individual differences. However, this did not seem to be case. Even though there were significant differences in mean scores between patients and controls for some of the psychological variables, the mean scores in the fibromyalgia group correspond more to "moderately high normal scores " than to scores from a psychiatrically ill population.
Some authors have claimed that the personality trait alexithymia, "no words for feelings" are common in fibromyalgia patients [46, 47]. This was not confirmed in our study, as no differences were seen in alexithymia scores. However, a high correlation was found between alexithymia scores and scores for anxiety, depression and neuroticism, which may indicate that alexithymia scores may be associated with psychological distress. Also previous studies have showed a strong association between alexithymia and depression and a general lack of absolute stability for the construct).)[48, 49].
Fibromyalgia patients scored moderately lower on internal health locus of control and higher on chance health locus of control than control subjects. The cognitive interpretation of this pattern could be something like: "Whatever I do, my illness just go on". The same pattern has been identified as being associated with reduced likelihood for engaging in healthy behaviour in young adults , but could in our opinion also be interpreted as an effect of chronic illness in the fibromyalgia patient sample.
The most powerful predictor for increased sensoric pain in fibromyalgia patients was a reduced drop in systolic blood pressure after buspirone challenge. One possible explanation for this finding is that fibromyalgia patients display perturbations in central sympathetic system with reduced reactivity, which might be due to reduced sensitivity of 5-HT1A receptors on sympathoexcitatory neurons in the rostral ventrolateral medulla. However, perturbations in the sympathetic-parasympathetic balance in fibromyalgia patients could also explain the results.
Our finding corresponds to previous findings suggesting alterations in autonomic regulation in fibromyalgia patients. Neuropeptide Y, which co-exists with norepinephrine in the sympathetic nervous system and may represent the sympathetic-neuronal output, has been found to be elevated in fibromyalgia patients . Also altered modulation of the sympathetic nervous system with deranged sympathetic response to orthostatic stress has previously been found in this patient group [21, 22].
Studies have provided convincing evidence that the adrenal gland is hypoactive in some stress-related states as posttraumatic stress disorder, in healthy individuals living under conditions of chronic stress as well as in patients with several bodily disorders including chronic fatigue syndrome, fibromyalgia, other somatoform disorders, rheumatoid arthritis, and asthma [24, 25, 51]. It has been hypothesized that a persistent lack of cortisol availability in traumatized or chronically stressed individuals may promote an increased vulnerability for the development of stress-related bodily disorders .
Our results partly confirm these previous results. Although there were no mean differences in baseline cortisol between fibromyalgia patients and control subjects, a negative association was found between pain and baseline cortisol. A trend was seen in the regression analysis between a small cortisol response to buspirone challenge and increased pain, but the cortisol responsiveness to serotonergic challenge only explained a minor and nonsignificant part of variance in pain. However, our methodology does not allow us to assess the relative importance of sympathetic dysregulation and relative adrenal insufficiency as cortisol and blood pressure responses to buspirone may not be truly independent variables. Corticosteroids may influence sympathetic neuronal excitability, and activity in the sympatho-adrenal system may influence cortisol secretion [52, 53].
In controls, a different pattern was seen than in fibromyalgia patients. Psychological distress was strongly associated with perceived pain, and only affective pain was found to be associated with autonomic reactivity. Our finding of a correlation between high drop in blood pressure and high affective pain may indicate an association between affective pain and high sympathetic reactivity in population controls. However, the small sample size implicates cautiousness in the interpretation of the results.
Some methodological weaknesses are present in this study. Pain and other symptoms in fibromyalgia patients may vary through the menstrual cycle . However, we were not able to control for this in our study. Buspirone has multiple pharmacological actions and may not be an ideal drug for pharmacological challenge, but was chosen because of its previous frequent use and known safety in human neuroendocrine studies. It is recognized that the first pass effect is extensive, and the major metabolite 1-(-2 pyrimdinyl) piperazine (1-PP) acts as a α2 adrenoceptor antagonist. This may interfere with the interpretation of the results on a receptor level, but it has no impact on our main conclusions. In this study we were not able to measure plasma levels of buspirone or its metabolites, and pharmacokinetic differences due to for instance differences in absorption between groups cannot be excluded. The relatively small sample size may also have lead to type two errors.
This study confirms that a biopsychosocial model is needed to explain variance in pain in fibromyalgia patients. Personality traits related to over-reactivity or over-responsiveness (neuroticism) and social conformity as well as factors related to perturbation of the autonomic nervous system and the HPA-axis explained a substantial part of variance of pain in the fibromyalgia patients. Neuroticism and psychological distress also were good predictors of variance in pain in population controls.
Malt EA, Berle J, Olafsson S, Lund A, Ursin H: Fibromyalgia is associated with panic disorder and functional dyspepsia with mood disorders. A study of women with random sample population controls. J Psychosom Res. 2000, 49: 285-289. 10.1016/S0022-3999(00)00139-2.
Tanum L, Malt UF: Sodium lactate infusion in fibromyalgia patients. Biol Psychiatry. 1995, 38: 559-561. 10.1016/0006-3223(95)00132-Z.
Martinez JE, Ferraz MB, Fontana AM, Atra E: Psychological aspects of Brazilian women with fibromyalgia Psychological aspects of Brazilian women with fibromyalgia. J Psychosom Res. 1995, 39: 167-174. 10.1016/0022-3999(94)00093-K.
Alfici S, Sigal M, Landau M: Primary fibromyalgia syndrome – a variant of depressive disorder?. Psychother Psychosom. 1989, 51: 156-161.
Kirmayer LJ, Robbins JM, Kapusta MA: Somatization and depression in fibromyalgia syndrome. Am J Psychiatry. 1988, 145: 950-954.
Epstein SA, Kay G, Clauw D, Heaton R, Klein D, Krupp L: Psychiatric disorders in patients with fibromyalgia. A multicenter investigation. Psychosomatics. 1999, 40: 57-63.
Hudson JI, Goldenberg DL, Pope HG, Keck PE, Schlesinger L: Comorbidity of fibromyalgia with medical and psychiatric disorders. Am J Med. 1992, 92: 363-367. 10.1016/0002-9343(92)90265-D.
McBeth J, Macfarlane GJ, Benjamin S, Morris S, Silman AJ: The association between tender points, psychological distress, and adverse childhood experiences: a community-based study. Arthritis Rheum. 1999, 42: 1397-1404. 10.1002/1529-0131(199907)42:7<1397::AID-ANR13>3.0.CO;2-7.
Walter B, Vaitl D, Frank R: Affective distress in fibromyalgia syndrome is associated with pain severity. Z Rheumatol. 1998, 57 (Suppl 2): 101-104. 10.1007/s003930050247.
Goldenberg DL: Psychologic studies in fibrositis. Am J Med. 1986, 81: 67-70. 10.1016/0002-9343(86)90879-X.
Walker EA, Keegan D, Gardner G, Sullivan M, Katon WJ, Bernstein D: Psychosocial factors in fibromyalgia compared with rheumatoid arthritis: I. Psychiatric diagnoses and functional disability. Psychosom Med. 1997, 59: 565-571.
Ahles TA, Yunus MB, Riley SD, Bradley JM, Masi AT: Psychological factors associated with primary fibromyalgia syndrome. Arthritis Rheum. 1984, 27: 1101-1106.
Anderberg UM, Forsgren T, Ekselius L, Marteinsdottir I, Hallman J: Personality traits on the basis of the Temperament and Character Inventory in female fibromyalgia syndrome patients. Nord J Psychiatry. 1999, 53: 353-359. 10.1080/080394899427827.
Ekselius L, Bentsson A, von Knorring L: Personality traits as determined by means of the Karolinska scales of personality in patients with fibromyalgia. J Musculoskel Pain. 1998, 6: 35-49.
Netter P, Hennig J: The fibromyalgia syndrome as a manifestation of neuroticism?. Z Rheumatol. 1998, 57 (Suppl 2): 105-108. 10.1007/s003930050248.
Ahles TA, Khan SA, Yunus MB, Spiegel DA, Masi AT: Psychiatric status of patients with primary fibromyalgia, patients with rheumatoid arthritis, and subjects without pain: a blind comparison of DSM-III diagnoses. Am J Psychiatry. 1991, 148: 1721-1726.
Spanjer J: [Is there a characteristic personality profile in patients with fibromyalgia? Study of achievement motivation and coping] Is er een kenmerkende persoonlijkheidsstructuur bij fibromyalgiepatienten? Onderzoek naar prestatiemotivatie en coping. Ned Tijdschr Geneeskd. 1994, 138: 2145-2149.
Anderberg UM, Liu Z, Berglund L, Nyberg F: Elevated plasma levels of neuropeptide Y in female fibromyalgia patients. Eur J Pain. 1999, 3: 19-30. 10.1016/S1090-3801(99)90185-4.
Cohen H, Neumann L, Kotler M, Buskila D: Autonomic nervous system derangement in fibromyalgia syndrome and related disorders. Isr Med Assoc J. 2001, 3: 755-760.
Cohen H, Neumann L, Alhosshle A, Kotler M, Abu-Shakra M, Buskila D: Abnormal sympathovagal balance in men with fibromyalgia. J Rheumatol. 2001, 28: 581-589.
Martinez-Lavin M, Hermosillo AG, Mendoza C, Ortiz R, Cajigas JC, Pineda C: Orthostatic sympathetic derangement in subjects with fibromyalgia. J Rheumatol. 1997, 24: 714-718.
Martinez-Lavin M, Hermosillo AG, Rosas M, Soto ME: Circadian studies of autonomic nervous balance in patients with fibromyalgia: a heart rate variability analysis. Arthritis Rheum. 1998, 41: 1966-1971. 10.1002/1529-0131(199811)41:11<1966::AID-ART11>3.3.CO;2-F.
Vaeroy H, Qiao ZG, Morkrid L, Forre O: Altered sympathetic nervous system response in patients with fibromyalgia (fibrositis syndrome). J Rheumatol. 1989, 16: 1460-1465.
Neeck G, Crofford LJ: Neuroendocrine perturbations in fibromyalgia and chronic fatigue syndrome. Rheum Dis Clin North Am. 2000, 26: 989-1002.
Griep E-N, Boersma J-W, De Kloet E-R: Altered reactivity of the hypothalamic-pituitary-adrenal axis in the primary fibromyalgia syndrome. J Rheumatol. 1993, 20: 469-474.
Crofford LJ, Pillemer SR, Kalogeras KT, Cash JM, Michelson D, Kling MA: Hypothalamic-pituitary-adrenal axis perturbations in patients with fibromyalgia. Arthritis Rheum. 1994, 37: 1583-1592.
Crofford LJ, Demitrack MA: Evidence that abnormalities of central neurohormonal systems are key to understanding fibromyalgia and chronic fatigue syndrome. Rheum Dis Clin North Am. 1996, 22: 267-284.
Pillemer SR, Bradley LA, Crofford LJ, Moldofsky H, Chrousos GP: The neuroscience and endocrinology of fibromyalgia. Arthritis Rheum. 1997, 40: 1928-1939.
Crofford L J: The hypothalamic-pituitary-adrenal stress axis in fibromyalgia and chronic fatigue syndrome. Z Rheumatol. 1998, 57 (Suppl 2): 67-71. 10.1007/s003930050239.
Anderberg UM: Fibromyalgia Syndrome in Women – a Stress Disorder? Neurobiological and Hormonal aspects. Uppsala University; Dissertation. 1999
Wolfe F, Smythe HA, Yunus MB, Bennett RM, Bombardier C, Goldenberg DL: The American College of Reheumatology 1990 criteria for the classification of fibromyalgia: report of the Multicenter Criteria Committee. Arthritis Rheum. 1990, 33: 160-172.
Strand LI, Wisnes AR: The development of a Norwegian pain questionnaire. Pain. 1991, 46: 61-66. 10.1016/0304-3959(91)90034-U.
Goldberg D, Williams P: A user's guide to the General Health Questionnaire. Windsor: NFER-Nelson;. 1988
Zigmond AS, Snaith RP: The hospital anxiety and depression scale. Acta Psychiatr Scand. 1983, 67: 361-370.
Eysenck H, Eysenck S: The manual for the Eysenck Personality Questionnaire. London: Hodder & Stoughton;. 1975
Taylor GJ, Bagby RM, Ryan DP: Criterion validity of the Toronto Alexithymia Scale. Psychosom Med. 1988, 50: 500-509.
Rotter JB: Generalized expectancies for internal versus external control of reinforcement. Psychol Monogr. 1966, 80:
Kubo T, Taguchi K, Ozaki S, Amano M, Ishizuka T: 8-OH-DPAT-induced hypotensive action and sympathoexcitatory neurons in the rostral ventrolateral medulla of the rat. Brain Res Bull. 1995, 36: 405-411. 10.1016/0361-9230(94)00221-L.
Lechin F, Van Der Dijs B, Jara H, Orozco B, Baez S, Benaim M, Lechin M, Lechin A: Effects of buspirone on plasma neurotransmitters in healthy subjects. J Neur Trans. 1998, 105 (Suppl 6-7): 561-573. 10.1007/s007020050079.
Maes M, Van Gastel A, Meltzer HY, Cosyns P, Blockx P, Desnyder R: Acute administration of buspirone increases the escape of hypothalamic-pituitary-adrenal-axis hormones from suppression by dexamethasone in depression. Psychoneuroendocrinology. 1996, 21: 67-81. 10.1016/0306-4530(95)00028-3.
Chua A, Keating J, Hamilton D, Keeling PW, Dinan TG: Central serotonin receptors and delayed gastric emptying in non-ulcer dyspepsia. BMJ. 1992, 305: 280-282.
Cowen PJ, Power AC, Ware CJ, Anderson IM: 5-HT1A receptor sensitivity in major depression. A neuroendocrine study with buspirone. Br J Psychiatry. 1994, 164: 372-379.
Dinan TG, Yatham LN, Barry S, Chua A, Keeling PW: Serotonin supersensitivity: the pathophysiologic basis of non-ulcer dyspepsia? A preliminary report of buspirone/prolactin responses. Scand J Gastroenterol. 1990, 25: 541-544.
Nyklicek I, Vingerhoets AJ: Alexithymia is associated with low tolerance to experimental painful stimulation. Pain. 2000, 85: 471-475. 10.1016/S0304-3959(99)00295-X.
Kurtze N, Gundersen KT, Svebak S: The role of anxiety and depression in fatigue and patterns of pain among subgroups of fibromyalgia patients. Br J Med Psychol. 1998, 71 (Pt 2): 185-194.
Brosschot JF, Aarsse HR: Restricted emotional processing and somatic attribution in fibromyalgia. Int J Psychiatry Med. 2001, 31: 127-146.
Leichner-Hennig R, Vetter GW: [Relation between pain experience and psychological markers in patients with fibrositis syndrome and patients with rheumatoid arthritis]. Z Rheumatol. 1986, 45: 139-145.
Honkalampi K, Hintikka J, Tanskanen A, Lehtonen J, Viinamaki H: Depression is strongly associated with alexithymia in the general population. J Psychosom Res. 2000, 48: 99-104. 10.1016/S0022-3999(99)00083-5.
Luminet O, Bagby RM, Taylor GJ: An evaluation of the absolute and relative stability of alexithymia in patients with major depression. Psychother Psychosom. 2001, 70: 254-260. 10.1159/000056263.
Steptoe A, Wardle J: Locus of control and health behaviour revisited: a multivariate analysis of young adults from 18 countries. Br J Psychol. 2001, 92 Part 4: 659-672. 10.1348/000712601162400.
Heim C, Ehlert U, Hellhammer DH: The potential role of hypocortisolism in the pathophysiology of stress-related bodily disorders. Psychoneuroendocrinology. 2000, 25: 1-35. 10.1016/S0306-4530(99)00035-9.
Joels M, Hesen W, de Kloet ER: Long-term control of neuronal excitability by corticosteroid hormones. J Steroid Biochem Mol Biol. 1995, 53: 315-323. 10.1016/0960-0760(95)00069-C.
Ehrhart-Bornstein M, Bornstein SR, Gonzalez-Hernandez J, Holst JJ, Waterman MR, Scherbaum WA: Sympathoadrenal regulation of adrenocortical steroidogenesis. Endocr Res. 1995, 21: 13-24.
Anderberg UM, Marteinsdottir I, Hallman J, Baeckstroem T: Variability in the cyclicity affects pain and other symptoms in female fibromyalgia syndrome patients. J Musculoskel Pain. 1998, 6: 5-22.
The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2474/3/12/prepub
This study was supported by grants from the University of Bergen. We are grateful to colleges who commented on the manuscript and to the subjects of the study for their time and patience.
Author 1 EAM participated in the design of the study, carried out the psychometric testing and the buspirone challenge test, performed the statistical analysis and drafted the manuscript. Author 2 SO participated in the design of the study and in the administration of the buspirone challenge test. Author 3 AL participated in the design of the study. Author 4 HU participated in the design and coordination of the study.