The following studies were published in the period January through December 2002. Abstracts for 2003 will be posted at intervals during the year. Similar collections of abstracts published in 1999, 2000 and 2001 can be found on the website of the National Fibromyalgia Partnership: www.fmpartnership.org.

PURPOSE: To assess the efficacy of fluoxetine in the treatment of patients with fibromyalgia. SUBJECTS AND METHODS: Sixty outpatients (all women, aged 21–71 years) with fibromyalgia were randomly assigned to receive fluoxetine (10–80 mg/d) or placebo for 12 weeks in a double-blind, parallel-group, flexible-dose study. The primary outcome measures were the Fibromyalgia Impact Questionnaire total score (score range, 0 [no impact] to 80) and pain score (score range, 0–10). Secondary measures included the McGill Pain Questionnaire, change in the number of tender points, and total myalgic score. RESULTS: In the intent-to-treat analysis, women who received fluoxetine (mean [± SD] dose, 45 ± 25 mg/d) had significant (p = 0.005) improvement in the Fibromyalgia Impact Questionnaire total score compared with those who received placebo, with a difference of -12 (95% confidence interval [CI]: -19 to -4). They also had significant (p = 0.002) improvement in the Fibromyalgia Impact Questionnaire pain score (difference, -2.2 [95% CI: -3.6 to -0.9]), as well as in the Fibromyalgia Impact Questionnaire fatigue (p = 0.05) and depression (p = 0.01) scores and the McGill Pain Questionnaire (p = 0.01), when compared with subjects who received placebo. Although counts for the number of tender points and total myalgic scores improved more in the fluoxetine group than in the placebo group, these differences were not statistically significant. CONCLUSIONS: In a 12-week, flexible-dose, placebo-controlled trial, fluoxetine was found to be effective on most outcome measures and generally well tolerated in women with fibromyalgia.

Somatosensory perception thresholds, perceived intensity, and quality of perceptions were assessed in 20 women with fibromyalgia syndrome (FMS) and in 20 healthy age-matched female controls. All patients and controls scaled perceived intensity and described perceived quality of randomized thermal (Thermotest) and tactile (von Frey filaments) stimulation. Perceived intensity was scaled by free-number magnitude estimation, and inter-individual comparability was accomplished by Master Scaling. Perceived quality was assessed by choosing verbal descriptors from a list. Thenar was used as a reference for each modality tested. All patients were able to reliably scale perceived intensity at thenar, as well as in pain-affected body areas. Perception thresholds for cold pain, heat pain, cold-pain tolerance and heat-pain tolerance were significantly lower in patients than controls. For cold and tactile stimulation, the master scaled perceived intensities were significantly higher in patients' pain-affected areas, whereas for warmth/heat stimulation, the intensities were significantly lower. In the qualitative perceptual analysis the most striking and significant finding was the aberration of cold-evoked perceptions in all patients: most stimuli in the range of 30–10 degrees C were reported as heat or other paresthetic or dysesthetic perceptions. The perceptual quality of warmth, and of touch, did not differ from the controls. Another aberration was observed in the nociceptive range of thermal and of tactile stimulation as significantly more frequent pain-related descriptors than in controls. This indicates a general nociceptive facilitation in addition to the lower thermal pain thresholds. The combination of cold hyperesthesia, cold dysesthesia, and multimodal hyperalgesia suggests a selective pathophysiology at a particular level of integration, possibly in the insular cortex. It is suggested that the aberrations revealed by the supraliminal sensory evaluation may be generic for FMS. Particularly, the aberrations established in all patients for perceived quality and intensity in the cold sensory channel may be an additional diagnostic criterion.

In this study, we evaluated pain sensitivity in patients with fibromyalgia or other types of chronic, diffuse musculoskeletal pain to establish whether fibromyalgia represents the end of a continuum of dysfunction in the nociceptive system. One hundred and forty-five patients and 22 healthy subjects (HS) completed an epidemiological questionnaire to provide information about fatigue, stiffness, sleep, the intensity of pain (VAS 0-100) and its extent both at onset and at present. Algometry was performed at all American College of Rheumatology (ACR) tender points and at ten control points. Patients were divided into five main groups: fibromyalgia (FS) patients, secondary-concomitant fibromyalgia (SCFS) patients, patients with widespread pain (WP) but not reaching the ACR criterion of 11 tender points, patients with diffuse multi-regional pain (MP) not reaching the ACR criteria (widespread pain, tender point counts), and patients with multi­regional pain associated with at least 11 tender points (MPTE). Von Frey monofilaments were used to assess superficial punctate pressure pain thresholds. Heat and cold pain thresholds were determined with a thermal stimulator. Ischemic pain was assessed by the cold pressure test and the submaximal effort tourniquet test. The scores for stiffness and present pain intensity gradually increased concomitantly with the increase in tender point count and pain extent. The pressure pain thresholds for positive tender and positive control points were significantly lower in the SCFS, FS and MPTE groups than in HS, MP and WP groups, the latter three groups displaying similar values. In all groups, there were no differences in pain thresholds between positive tender and positive control points. The heat pain threshold and the pain threshold in the cold pressure test were lower in the FS and SCFS groups than in HS. The cold pressure tolerance was lower in patients with widespread pain than in HS. In the von Frey test, all patient groups except MP had similar values, which were significantly lower than in HS. Finally, all patient groups displayed lower tourniquet tolerance than HS. In each psychophysical test, patients with widespread pain and patients with multi­regional pain showed similar thresholds; however, the thresholds in the MP or MPTE groups differed from those in the FS and SCFS groups. In the FS group, pain thresholds and pain tolerance did not differ according to the presence of ongoing pain at the stimulated site and were not correlated to ongoing pain. The results indicate that dysfunction in the nociceptive system is already present in patients with multiregional pain with a low tender point count; it becomes more and more severe as the positive tender point count and pain extent increase and it is maximal in fibromyalgia patients.

OBJECTIVES: To investigate whether chronic pain patients have deficits in attentional functioning compared with pain-free controls, and whether fibromyalgia patients have larger deficits in attentional functioning compared with rheumatoid arthritis and musculoskeletal pain patients. METHODS: Sixty patients (20 in each of 3 patient groups) and 20 pain-free controls completed measures assessing pain intensity, mood, pain-related disability, somatic awareness, and catastrophic thinking about pain. Attentional functioning was assessed using an age-standardized, ecologically valid test battery. Analyses were made of between-group differences. RESULTS: Sixty percent of patients had at least one score in the clinical range of neuropsychological impairment, independent of demography and mood. Fibromyalgia patients were more anxious and somatically aware than rheumatoid arthritis or musculoskeletal pain patients, but did not show larger attentional deficits than other patient groups. CONCLUSION: All 3 groups of chronic pain patients, regardless of diagnosis, had impaired cognitive functioning on an ecologically sensitive neuropsychological test of everyday attention.

OBJECTIVE: To use functional magnetic resonance imaging (fMRI) to evaluate the pattern of cerebral activation during the application of painful pressure and determine whether this pattern is augmented in patients with fibromyalgia (FM) compared with controls. METHODS: Pressure was applied to the left thumbnail beds of 16 right-handed patients with FM and 16 right-handed matched controls. Each FM patient underwent fMRI while moderately painful pressure was being applied. The functional activation patterns in FM patients were compared with those in controls, who were tested under 2 conditions: the "stimulus pressure control" condition, during which they received an amount of pressure similar to that delivered to patients, and the "subjective pain control" condition, during which the intensity of stimulation was increased to deliver a subjective level of pain similar to that experienced by patients. RESULTS: Stimulation with adequate pressure to cause similar pain in both groups resulted in 19 regions of increased regional cerebral blood flow in healthy controls and 12 significant regions in patients. Increased fMRI signal occurred in 7 regions common to both groups, and decreased signal was observed in 1 common region. In contrast, stimulation of controls with the same amount of pressure that caused pain in patients resulted in only 2 regions of increased signal, neither of which coincided with a region of activation in patients. Statistical comparison of the patient and control groups receiving similar stimulus pressures revealed 13 regions of greater activation in the patient group. In contrast, similar stimulus pressures produced only 1 region of greater activation in the control group. CONCLUSION: The fact that comparable subjectively painful conditions resulted in activation patterns that were similar in patients and controls, whereas similar pressures resulted in no common regions of activation and greater effects in patients, supports the hypothesis that FM is characterized by cortical or sub­cortical augmentation of pain processing.

OBJECTIVE: Fibromyalgia (FM) is a chronic, painful musculoskeletal disorder characterized by widespread pain, pressure, hyperalgesia, morning stiffness, and an increased incidence of depressive symptoms. The etiology, however, has remained elusive. The aim of the present study was to examine the inflammatory response system in FM and to investigate the effect of depression level on serum cytokines. METHODS: Serum interleukin-1 (IL-1), IL-2 receptor (IL-2r), IL-6, and IL-8 and the Hamilton Depression Rating Scale (HDRS) score were determined in 32 healthy volunteers and in 81 patients with FM, classified according to the American College of Rheumatology criteria. RESULTS: In our study, serum IL-1 and IL-6 were not statistically significant, but serum IL-8, IL2r, and HDRS score were significantly higher in patients with FM than the control group (p < 0.01). In addition, in patients with FM, IL-8 was found to be related to pain intensity (r = 0.35; p < 0.01). CONCLUSION: IL-8 may play an important role in the occurrence of pain in FM.

OBJECTIVE: To determine whether there is any difference in regional cerebral blood flow (rCBF) and serum cytokine levels and association between clinical parameters and rCBF and serum cytokine levels in young females with fibromyalgia (FM). The other aim was to search whether the depression state has any effect on these two parameters. METHODS: Nineteen women with FM and 20 healthy women had 99mTc-HMPAO brain single-photon-emission computed tomography (SPECT) to evaluate rCBF. Serum interleukin (IL) levels (IL 1 beta, IL 2r, IL 6 and IL 8) were measured. Clinical and psychological evaluation was also carried out in FM patients and healthy controls. RESULTS: The patients with FM had significantly higher radioactivity uptake ratio in right and left caudate nucleus (p = 0.009, p = 0.001, respectively) than healthy controls. There was statistically significant decrease in the 99mTc-HMPAO uptake in the right superior parietal (p = 0.041), gyrus rectalis (p = 0.036) and pons (p = 0.023). FM patients had significantly higher serum IL 2r and IL 8 levels (p = 0.023, p = 0.011, respectively) than controls. Additionally, FM patients had significantly higher Fibromyalgia Impact Questionnaire (FIQ), Health Assessment Questionnaire (HAQ), and Hamilton Depression Rate scale (HDRS) scores (p = 0.000) than controls. Interestingly, the patients with mild depressive symptoms or without (i.e. HDRS-score < or = 16) had significantly higher serum IL 8 levels (p = 0.027) and increased radioactivity uptake ratio in the pons (p = 0.036) than the patients with more severe depressive symptoms (i.e. HDRS-score > 16). With regard to regional cerebral blood flow, significant correlations were detected between RSP and morning stiffness (r = 0.70, p < 0.01) and sleep disturbance (r = -0.53, p < 0.05), and between gyrus rectalis and FIQ score. There were significant correlations between LCN and IL-2 (p = 0.025), between RSP and morning stiffness (p = 0.006), sleep disturbance (p = 0.021) according to multiple regression analysis test[ing]. CONCLUSION: This study shows a significant increase in rCBF of caudate nuclei, a reduction in the pons, some cortical regions activity and a increase in IL 8, IL2r levels of young female patients with FM. These findings are more prominent in patients with low HDRS scores.

OBJECTIVE: To quantify the serum levels of the advanced glycation end-product (AGE) pentosidine in 41 patients with fibromyalgia ( FM) and 46 healthy controls. The formation of pentosidine is closely related to oxidative stress. METHODS: Pentosidine was measured by reverse-phased high-performance liquid chromatography with gradient separation on a RP-18 column. RESULTS: Patients with FM have significantly higher pentosidine serum levels than healthy subjects. CONCLUSION: AGE modification of proteins leads to reduced solubility and high resistance to proteolytic digestion of such altered proteins (e.g. AGE-modified collagens). AGEs are also able to stimulate different kinds of cells via activation of the NFkappaB, mediated by specific receptors of AGEs (e.g. RAGE) on the cell surface. Both mechanisms may contribute to the development, perpetuation and spreading of pain phenomena in FM patients.

OBJECTIVE: To determine the effectiveness of a muscle strengthening program compared to a stretching program in women with fibromyalgia (FM). METHODS: Sixty-eight women with FM were randomly assigned to a 12-week, twice weekly exercise program consisting of either muscle strengthening or stretching. Outcome measures included muscle strength (main outcome variable), flexibility, weight, body fat, tender point count, and disease and symptom severity scales. RESULTS: No statistically significant differences between groups were found on independent t tests. Paired t tests revealed twice the number of significant improvements in the strengthening group compared to the stretching group. Effect size scores indicated that the magnitude of change was generally greater in the strengthening group than the stretching group. CONCLUSION: Patients with FM can engage in a specially tailored muscle strengthening program and experience an improvement in overall disease activity, without a significant exercise induced flare in pain. Flexibility training alone also results in overall improvements, albeit of a lesser degree.

OBJECTIVE: In this study of female home care personnel employed in a municipality (N = 643; participation rate 94%) we investigated (1) the prevalence of tender points and fibromyalgia (FM); (2) the relationships between tender point score and other signs and symptoms; (3) if subgroups based on the tender point score differed with respect to signs, symptoms, disability, and health related quality of life; and (4) signs that showed the strongest intercorrelations with disability and health. METHODS: The following variables were registered: (1) Signs: joint mobility, spinal posture and mobility, tender points, and segmental mobility and pain provocation at L4-S1 levels of the low back. (2) Symptoms: pain and pain intensity and other symptoms. (3) Disability (i.e., self-rated reduced capacity for everyday activities and employment) and health: 3 indices and sick leave. RESULTS: The tender point score correlated with the number of pain regions and the pain intensities, and the amount of other symptoms, sick leave, and disability. Tender point score was the strongest regressor of the investigated signs in regression of the 2 disability indices. Segmental pain showed the strongest correlation with tender point score. Three subgroups identified by tender point score showed significant differences in segmental pain, prevalence and intensity of different symptoms, disability, and health-related quality of life. The prevalence of FM was 2.0%. CONCLUSION: Tender point score together with different symptoms showed relatively strong correlations with disability. A relatively high prevalence of FM was found in occupationally active female home care personnel.

BACKGROUND: Fibromyalgia syndrome displays sympathetically maintained pain features such as frequent post-traumatic onset and stimuli-independent pain accompanied by allodynia and paresthesias. Heart rate variability studies showed that fibromyalgia patients have changes consistent with ongoing sympathetic hyperactivity. [In this study, a] norepinephrine-evoked pain test is used to assess sympathetically maintained pain syndromes. Our objective was to define if fibromyalgia patients have norepinephrine-evoked pain. METHODS: Prospective double blind controlled study. Participants: Twenty FM patients, and two age/sex matched control groups: 20 rheumatoid arthritis patients and 20 healthy controls. Ten micrograms of norepinephrine diluted in 0.1 ml of saline solution were injected in a forearm. The contrasting substance, 0.1 ml of saline solution alone, was injected in the opposite forearm. Maximum local pain elicited during the 5 minutes post-injection was graded on a visual analog scale (VAS). Norepinephrine-evoked pain was diagnosed when norepinephrine injection induced greater pain than placebo injection. Intensity of norepinephrine-evoked pain was calculated as the difference between norepinephrine minus placebo-induced VAS scores. RESULTS: Norepinephrine-evoked pain was seen in 80% of FM patients (95% confidence intervals 56.3 – 94.3), in 30% of rheumatoid arthritis patients and in 30% of healthy controls (95% confidence intervals 11.9 – 54.3) (p < 0.05). Intensity of norepinephrine-evoked pain was greater in FM patients (mean ± SD 2.5 ± 2.5) when compared to rheumatoid arthritis patients (0.3 ± 0.7), and healthy controls (0.3 ± 0.8) (p < 0.0001). CONCLUSIONS: Fibromyalgia patients have norepinephrine-evoked pain. This finding supports the hypothesis that fibromyalgia may be a sympathetically maintained pain syndrome.

OBJECTIVE: To evaluate literature that discusses the treatment of fibromyalgia syndrome (FMS) with agents that involve the neurotransmitter serotonin. DATA SOURCES: Biomedical literature accessed through MEDLINE (1966–August 2001) and International Pharmaceutical Abstracts. DATA SYNTHESIS: The cause and pathophysiology of FMS remain elusive, although abnormalities in the serotonin pathway have been implicated. Several serotonergic agents have been studied for use in FMS. Trials and case reports focusing on the use of newer agents: the selective serotonin reuptake inhibitors, venlafaxine and tramadol, were reviewed. CONCLUSIONS: Current research suggests that the serotonergic agents may reduce at least some of the symptoms of FMS. However, medications that act on multiple neurotransmitters may prove to be more effective in symptom management. Additional long-term studies are required in order to validate these results.

OBJECTIVE: The purpose of this review was to determine how effective different classes of analgesic agents are in the management of chronic pain. METHODOLOGY: The literature search identified five systematic reviews and 18 randomized controlled trials to provide evidence about systemic drug treatment for chronic pain. RESULTS: Studies in the systematic reviews were mainly of low back pain, and studies in the randomized controlled trials were mainly of fibromyalgia. Other studies investigated rheumatic pain, musculoskeletal pain, chronic low back pain, and temporomandibular pain. Classes of analgesic agents reviewed were antidepressants, nonsteroidal anti-inflammatory drugs, muscle relaxants, opioid analgesics, and a number of miscellaneous agents. CONCLUSIONS: For chronic pain, opioid analgesics provide benefit for up to 9 weeks (level 2). For chronic low back pain, the evidence shows that various types of nonsteroidal anti-inflammatory drugs are equally effective or ineffective, and that antidepressants provide no benefit in the short to intermediate term (level 2). Muscle relaxants showed limited effectiveness (level 3) for chronic neck pain and for chronic low back pain for up to 4 weeks. For fibromyalgia, there is limited evidence (level 3) of the effectiveness of amitryptiline, ondansetron, zolpidem, or growth hormone, and evidence of no effectiveness for nonsteroidal anti-inflammatory drugs, malic acid with magnesium, calcitonin injections, or s-adenyl-L-methionine. For temporomandibular pain, oral sumatriptan is not effective (level 2). The remaining evidence was inadequate (level 4a) or contradictory (level 4b).

BACKGROUND: To investigate the effects of intravenous lignocaine infusions (IV lignocaine) in fibromyalgia. METHODS: Prospective study of the adverse effects of IV lignocaine in 106 patients with fibromyalgia; retrospective questionnaire study of the efficacy of IV lignocaine in 50 patients with fibromyalgia. RESULTS: Prospective study: Two major (pulmonary oedema and supra­ventricular tachycardia) and 42 minor side-effects were reported. None had long-term sequelae. The commonest was hypotension (17 cases). Retrospective study: Pain and a range of psychosocial measures (on single 11-point scales) improved significantly after treatment. There was no effect of the treatment on work status. The average duration of pain relief after the 6-day course of treatment was 11.5 ±; 6.5 weeks. CONCLUSIONS: Intravenous lignocaine appears to be both safe and of benefit in improving pain and quality of life for patients with fibromyalgia. This needs to be confirmed in prospective randomised controlled trials.

Pain is perceived, transmitted, processed and modulated within an extensive network of neurotransmitters and hormones. Despite increasing knowledge about the biologic principles, even on the molecular level, the more we learn about the precise mechanisms of their interactions the more questions arise. It is also pertinent to remember that clinical scientists studying pain modulating pharmacologic agents always have to consider possible placebo effects [57–61]. Most of our knowledge regarding the function of neurotransmitter systems in the CNS has been provided by animal studies. Thus we cannot be sure that they have exactly parallel counterparts in humans. For instance, animal studies suggest an inverse relationship between brain and spinal cord concentrations of substance P. If these observations are converted to an interpretation of human fibromyalgia, low brain-tissue levels of both serotonin and substance P should be expected, while spinal cord serotonin concentrations would be low and spinal cord substance P would be high [1]. There is good evidence that 5-HT, its receptors, and their interactions with other neurotransmitters are essential for nociception and antinociception. The activities of 5-HT receptors can be studied by agonist and, in humans especially, by antagonist use. But even with a direct spinal application of selective agonists and antagonists, observations may still be confounded by (1) dose, as there can be a dose-dependent activation of different receptor subtypes; (2) type of nociceptive tests (e.g., thermal versus pressure versus chemical models), which may have differences in the way they are regulated; and (3) influences due to effects on temperature, blood flow or motor function. With this potential for variability, it is perhaps not surprising that there is some variability in the results of studies reporting on the effects of various 5-HT agonists and antagonists on nociceptive transmission within the spinal cord [62]. For instance, different 5-HT3 receptor densities could exist in various neuronal systems, one density type being completely inhibited at low concentrations, and the others only at higher concentrations of 5-HT3 receptor antagonists, thus resulting in contrary effects. Finally, the "endogeneous 5-HT tone" may greatly influence agonist and antagonist action. Considering this complexity of serotonin-mediated reactions, it is not surprising that treatment of pain by 5-HT3 receptor antagonists appears to yield inconsistent results. As fibromyalgia is now regarded as a pain amplification syndrome with a broad variety of additional non-pain symptoms, the interrelations are complicated even more. Fibromyalgia associated symptoms (e.g., fatigue, insomnia, and irritable bowel syndrome) can be modulated by 5-HT3 receptor antagonists. From the data evaluated so far, there is evidence that 5-HT3 receptor antagonists provide significant benefit in some fibromyalgia patients. In our practice, the data justify a careful application in clinical use according to the study results. The dosage, route of application, long term adverse reactions and duration of therapy still need to be studied in greater detail. Recently reported adverse events from therapy of irritable bowel syndrome with alosetron [63–67] provide a note for caution before hastily using 5-HT3 receptor antagonists without more studies. One can surmise that, much as the biochemistry of depression has been elucidated by the development of the SSRIs, a greater understanding of the role of 5-HT3 receptor antagonists in treating fibromyalgia patients may provide some insights into disease mechanisms of this enigmatic disorder.

Fibromyalgia syndrome (FMS) is characterized by widespread pain, fatigue, sleep abnormalities, and distress. Because FMS lacks consistent evidence of tissue abnormalities, recent investigations have focused on central nervous system mechanisms of pain. Abnormal temporal summation of second pain (wind-up) and central sensitization have been described recently in patients with FMS. Wind-up and central sensitization, which rely on central pain mechanisms, occur after prolonged C-nociceptor input and depend on activation of nociceptor-specific neurons and wide dynamic range neurons in the dorsal horn of the spinal cord. Other abnormal central pain mechanisms recently detected in patients with FMS include diffuse noxious inhibitory controls. These pain inhibitory mechanisms rely on spinal cord and supraspinal systems involving pain facilitatory and pain inhibitory pathways. Brain-imaging techniques that can detect neuronal activation after nociceptive stimuli have provided additional evidence for abnormal central pain mechanisms in FMS. Brain images have corroborated the augmented reported pain experience of patients with fibromyalgia during experimental pain stimuli. In addition, thalamic activity, which contributes significantly to pain processing, was decreased in fibromyalgia. However, central pain mechanisms of fibromyalgia may not depend exclusively on neuronal activation. Neuroglial activation has been found to play an important role in the induction and maintenance of chronic pain. These findings may have important implications for future research and the treatment of fibromyalgia pain.

OBJECTIVE: To evaluate the influence of the weather in Cordoba City, Argentina, on pain in patients with rheumatic pain; to correlate different climate variables with the patients' impression of weather sensitivity; and to assess correlations between pain and climate conditions on 5 days preceding and following painful episodes. METHODS: Self-reported questionnaires to assess the presence and features of spontaneous daily pain during one year (1998) were completed by 151 outpatients with osteoarthritis (OA) (n = 52), rheumatoid arthritis (RA) (n = 82), and fibromyalgia (FM) (n = 17) and 32 healthy subjects. Data were correlated with daily temperature, atmospheric pressure, and relative humidity obtained during the same period. Only p values < 0.001 were considered significant. RESULTS: Low temperature, high atmospheric pressure, and high humidity were significantly correlated with pain in RA (r = -0.30, r = 0.34, r = 0.23, respectively; p < 0.001); in OA, pain correlated with low temperature and high humidity (r = –0.23, r = 0.24; p < 0.001); in FM, [pain correlated] with low temperature and high atmospheric pressure (r = -0.255, r = 0.22; p < 0.001) and no correlation was found in controls. Patients self-described as being weather sensitive correlated only with high humidity (r = 0.45; p < 0.001). There was no better correlation with climate variables, except for humidity, 5 days before or after the day of the painful episode. CONCLUSION: These results support the belief that weather influences rheumatic pain, albeit in different ways depending on the subjacent pathology and subjective weather sensitivity. This influence may not depend on weather conditions of the previous or following days, indicating that climate would not be a pain predictor and vice versa.