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Abstract

Iron deficiency and iron deficiency anaemia are frequently under-recognised in chronic conditions with non-specific symptoms, including fatigue. This study aimed to assess the prevalence of iron deficiency with or without anaemia in chronic pain patients, and the association between iron deficiency status, fatigue and health-related quality of life. Eighty-two patients attending chronic pain outpatient appointments were recruited into this cross-sectional study. Iron studies and haemoglobin were determined from venous blood samples. Participants’ health-related quality of life was assessed with the 36-item short form survey and fatigue with the functional assessment of chronic illness therapy fatigue scale. Iron deficiency was prevalent in 58.8% of patients and 2.5% met the criteria for iron deficiency anaemia. There was no significant association between iron deficiency status and the functional assessment of chronic illness therapy fatigue scale score or 36-item short form survey domain scores. There was a high prevalence of iron deficiency in this group of chronic pain patients, while the prevalence of iron deficiency anaemia was low. There was no statistically significant association found between iron deficiency status and fatigue or quality of life measures.

Keywords

Pain chronic anaemia iron deficiency fatigue quality of life patient-reported outcome measures

Introduction

Iron deficiency anaemia (IDA) is a significant risk factor for morbidity and mortality and is recognised as a global health problem.¹ Anaemia, defined as low concentrations of haemoglobin, affects about 23.2% of the global population.² While there is substantial geographical variation in the prevalence of anaemia, iron deficiency (ID) remains the leading cause of anaemia worldwide.² Data on the prevalence of IDA in the general Australian population is limited; however, the World Health Organization estimates a 17% prevalence of anaemia in non-pregnant Australian women aged 15–49 years.¹ A study in Queensland, Australia, reported that 10.6% of adult women under 50 years had severe ID, 2.8% for women 50 years and above and almost zero for men.³

Iron deficiency with or without anaemia is often under-diagnosed and under-treated in chronic conditions, including chronic heart failure,⁴ inflammatory bowel disease⁵ and chronic kidney disease.⁶ Iron deficiency, before the development of anaemia, is associated with impaired immune function,^7,8 decreased physical work capacity,⁹ impaired cognitive function^10
–12 and fatigue.^13
–15

Chronic pain, defined by the International Association of the Study of Pain, is pain that persists for more than 3 months,¹⁶ and has a prevalence of approximately 20% in developed countries.^17
–19 Chronic pain is associated with significant morbidity including depression,²⁰ fatigue,²¹ reduced health-related quality of life²² and impaired cognitive functioning.^23
–25 Creavin et al. reported that 64% of adults in the general population with chronic widespread pain experienced persistent fatigue.²⁶ It is therefore important to assess the potential contribution of ID to the high burden of fatigue in these patients.

Few studies have assessed the relationship between ID and chronic pain conditions. Ortancil et al. hypothesised that iron deficiency may play a role in the pathophysiology of fibromyalgia as the cerebrospinal fluid of fibromyalgia patients showed decreased concentrations of neurotransmitters synthesised from iron.^27,28 However, studies have both supported^27,29 and reported no evidence^30
–32 of an association between fibromyalgia and ID. The link between IDA and migraine is more consistent, with four studies supporting an association.^33
–36

Patient-reported outcome measures have increasingly gained importance in the evaluation of treatment in chronic pain clinics.^37
–39 In this study we evaluated the prevalence of ID in the setting of chronic pain patients with the aim of assessing the relationship between ID and health-related quality of life measures.

Methods

This cross-sectional study was conducted at the Royal Brisbane and Women’s Hospital (RBWH), a tertiary level hospital in Queensland, Australia. This study was approved by the Royal Brisbane and Women’s Hospital Human Research Ethics Committee (HREC/2019/QRBW/58663).

Patients presenting to the Professor Tess Cramond Multidisciplinary Pain Centre were screened for eligibility by trained research personnel. Patients over 18 years of age experiencing chronic pain for more than 12 months were included. Patients with known or suspected blood disorders, pregnant patients, patients taking iron supplementation including intravenous iron, or patients who underwent surgery within the past 6 months were excluded from the study.

Patients were recruited from the outpatient clinic or telephoned prior to their visit to obtain informed written consent. Non-fasting venous blood samples were taken on the day of the appointment by trained staff to determine their full blood count, serum iron, serum ferritin and serum transferrin. Iron deficiency anaemia was defined as ferritin less than 100 μg/l and haemoglobin less than 130 g/l in men or less than 120 g/l in women. Iron deficiency was defined as moderate if ferritin was less than 100 μg/l or severe if ferritin was less than 30 μg/l as per Queensland Health definitions.

Patient demographics and clinical information were collected by way of a written questionnaire and collated using REDCap software (Research Electronic Data Capture Vanderbilt) administered by Metro North Hospital and Health Services.⁴⁰ Data included the type of chronic pain condition and duration, medical comorbidities, medications, diet and alcohol intake. Pain was rated out of 10 using a visual numerical scale. Health-related quality of life was assessed by the 36-item short form survey (SF-36) and fatigue levels were assessed by the functional assessment of chronic illness therapy fatigue scale (FACIT-Fatigue).

The FACIT-Fatigue scale is a 13-item survey designed to assess the impact of fatigue in chronic disease. This measure has been validated in the chronic disease population and patients with IDA.^41
–43 Scores range from 0 to 52, with a higher score indicating less burden from fatigue. The SF-36 is a generic, self-administered questionnaire, which has been validated and used to assess treatment in chronic pain and other diverse populations.^{37
–39,44,45} The SF-36 provides domain scores rather than an overall score. The eight domains are physical functioning, role limitations due to physical health, role limitations due to emotional problems, fatigue, emotional wellbeing, social functioning, pain and general health. The scores range from 0 to 100, with the maximum score reflecting the highest quality of life. The scores are scaled to represent the average for all eight domains.

Statistical analyses were performed in STATA 15 (StataCorp, 2017. Stata Statistical Software: release 15, College Station, TX, USA: StataCorp LLC). Data were presented as mean and standard deviation (SD) for continuous normally distributed variables, median and interquartile range (IQR) for continuous non-normally distributed variables and frequency and percentage for categorical variables. Associations between categorical variables were assessed using chi-square tests and Fisher’s exact tests were used for small cell counts. To compare continuous normally distributed variables between two groups, the Student’s t-test was used, while a one-way analysis of variance was used to compare three groups. A Mann–Whitney U test (for comparison of two groups) or a Kruskal–Wallis test (for comparing three groups) was implemented if the continuous variable was not normally distributed. Associations between two continuous variables were explored using Pearson’s correlations. When the assumptions of the test did not hold, Spearman’s correlation was used. Statistical significance was defined as a P value less than 0.05 (two-sided).

Results

Eighty-two patients were recruited into this study between June and December 2020. Of these, two did not have ferritin measures available for the classification of ID, and three did not have both ferritin and haemoglobin measures available for the classification of IDA. The prevalence of ID was 58.8% (47/80), of which 37 (46.3%) were moderate in severity and 10 (12.5%) were severe. The prevalence of those with IDA was 2.5% (2/79).

There was no statistically significant association found between ID and age, gender, body mass index, medical comorbidities or medications. Iron deficiency was associated with decreased alcohol intake and eating meat and poultry consumed more than three times a week (Table 1). However, the small sample size and large number of simultaneous comparisons limits the interpretation of these results. No statistical association was found with other dietary factors including the patient’s subjective global assessment of their nutritional status.

Table 1.

Patient characteristics and iron status.

	Total	Not iron deficient	Iron deficient	P value
	N = 80	N = 33	N = 47	P value
Age, years, mean (SD)	57.7 (13.2)	58.8 (13.5)	56.9 (13.1)	0.52
BMI, kg/m², median (IQR)	30 (26–33.5)	30 (28–33)	28 (25–34)	0.23
BMI, kg/m²				0.41
<25 kg/m²	14 (18%)	3 (9%)	11 (23%)
25–29 kg/m²	24 (30%)	11 (33%)	13 (28%)
30–34 kg/m²	23 (29%)	11 (33%)	12 (26%)
≥35 kg/m²	19 (24%)	8 (24%)	11 (23%)
Gender				0.95
Male	44 (55%)	18 (55%)	26 (55%)
Female	36 (45%)	15 (45%)	21 (45%)
Alcohol use, standard drinks/week				0.039
None	34 (43%)	12 (36%)	22 (47%)
1–6	24 (30%)	7 (21%)	17 (36%)
>=7	22 (28%)	14 (42%)	8 (17%)
Cardiac disease				0.90
No	37 (46%)	15 (45%)	22 (47%)
Yes	43 (54%)	18 (55%)	25 (53%)
Respiratory disease				0.19
No	55 (69%)	20 (61%)	35 (74%)
Yes	25 (31%)	13 (39%)	12 (26%)
Diabetes mellitus				0.18
No	70 (88%)	31 (94%)	39 (83%)
Yes	10 (13%)	2 (6%)	8 (17%)
Central nervous system disease				0.18
No	70 (88%)	31 (94%)	39 (83%)
Yes	10 (13%)	2 (6%)	8 (17%)
Deep vein thrombosis				0.64
No	76 (95%)	32 (97%)	44 (94%)
Yes	4 (5%)	1 (3%)	3 (6%)
Malignancy				0.75
No	69 (86%)	28 (85%)	41 (87%)
Yes	11 (14%)	5 (15%)	6 (13%)
Substance abuse				0.71
No	72 (90%)	29 (88%)	43 (91%)
Yes	8 (10%)	4 (12%)	4 (9%)
Autoimmune disease				0.26
No	72 (90%)	28 (85%)	44 (94%)
Yes	8 (10%)	5 (15%)	3 (6%)
Gastrointestinal disease				0.69
No	74 (93%)	30 (91%)	44 (94%)
Yes	6 (8%)	3 (9%)	3 (6%)
Psychotropics				0.23
No	47 (59%)	22 (67%)	25 (53%)
Yes	33 (41%)	11 (33%)	22 (47%)
Agents for neuropathic pain				0.65
No	34 (43%)	15 (45%)	19 (40%)
Yes	46 (57%)	18 (55%)	28 (60%)
Other analgesia				0.62
No	51 (64%)	20 (61%)	31 (66%)
Yes	29 (36%)	13 (39%)	16 (34%)
NSAIDs (n = 79)				0.83
No	54 (68%)	23 (70%)	31 (67%)
Yes	25 (32%)	10 (30%)	15 (33%)
SSRI				0.40
No	75 (94%)	32 (97%)	43 (91%)
Yes	5 (6%)	1 (3%)	4 (9%)
SNRI				0.059
No	59 (74%)	28 (85%)	31 (66%)
Yes	21 (26%)	5 (15%)	16 (34%)
Leafy greens consumed >3 times weekly				0.17
No	16 (20%)	9 (27%)	7 (15%)
Yes	64 (80%)	24 (73%)	40 (85%)
Meat and poultry consumed >3 times weekly				0.001
No	7 (9%)	7 (21%)	0 (0%)
Yes	73 (91%)	26 (79%)	47 (100%)
Liver consumed >3 times weekly				0.57
No	77 (96%)	31 (94%)	46 (98%)
Yes	3 (4%)	2 (6%)	1 (2%)
Seafood consumed >3 times weekly				0.27
No	63 (79%)	24 (73%)	39 (83%)
Yes	17 (21%)	9 (27%)	8 (17%)
Beans consumed >3 times weekly				0.12
No	47 (59%)	16 (48%)	31 (66%)
Yes	33 (41%)	17 (52%)	16 (34%)
Subjective global assessment				0.32
A Well-nourished	75 (94%)	32 (97%)	43 (91%)
B Mildly/moderately malnourished	5 (6%)	1 (3%)	4 (9%)

n (%) presented unless otherwise specified.

BMI: body mass index; NSAIDs: non-steroidal anti-inflammatory drugs; SSRI: selective serotonin reuptake inhibitor; SNRI: serotonin and norepinephrine reuptake inhibitor; SD: standard deviation; IQR: interquartile range.

The associations between iron deficiency status, patient characteristics and the outcomes of FACIT-Fatigue were explored (Table 2). The presence of central nervous system disease, deep vein thrombosis and psychotropics were associated with lower FACIT-Fatigue scores, demonstrating a higher burden of fatigue. The mean difference in FACIT-Fatigue between ID and non-ID patients was –1.59 (95% confidence interval (CI) –6.46 to 3.28).

Table 2.

Association between iron deficiency and patient characteristics with FACIT-Fatigue.

	n	FACIT-Fatigue
	n	Mean (SD)	P value
Total	81	30.8 (10.6)
Iron deficiency			0.52
No	33	31.7 (10.7)
Yes	46	30.1 (10.8)
Sex			0.75
Male	45	31.2 (10.0)
Female	36	30.4 (11.3)
Alcohol use (standard drinks/week)			0.79
None	35	29.9 (10.5)
1–6	24	31.1 (11.7)
>=7	22	31.9 (9.7)
Cardiac disease			0.94
No	39	30.7 (10.1)
Yes	42	30.9 (11.1)
Respiratory disease			0.99
No	55	30.8 (10.1)
Yes	26	30.8 (11.6)
Diabetes			0.28
No	72	31.3 (10.7)
Yes	9	27.2 (9.5)
Central nervous system disease			0.020
No	71	31.8 (10.4)
Yes	10	23.6 (9.2)
Deep vein thrombosis			0.050
No	77	31.3 (10.5)
Yes	4	20.8 (7.7)
Malignancy			0.54
No	69	31.1 (10.2)
Yes	12	29.1 (12.6)
Substance abuse			0.82
No	73	30.9 (10.5)
Yes	8	30.0 (11.9)
Autoimmune disease			0.59
No	73	31.0 (10.5)
Yes	8	28.9 (11.1)
Gastrointestinal disease			0.76
No	76	30.9 (10.7)
Yes	5	29.4 (8.9)
Medications that affect coagulation			0.095
No	34	33.1 (10.2)
Yes	47	29.1 (10.6)
Psychotropics			0.037
No	48	32.8 (10.6)
Yes	33	27.9 (9.9)
Narcotics			0.064
No	45	32.8 (9.9)
Yes	36	28.4 (11.0)
Agents for neuropathic pain			0.68
No	34	31.4 (11.0)
Yes	47	30.4 (10.3)
Other analgesia			0.74
No	51	31.1 (10.2)
Yes	30	30.3 (11.3)
NSAIDs			0.27
No	55	31.5 (10.5)
Yes	25	28.7 (10.5)
SSRI			0.24
No	76	31.2 (10.7)
Yes	5	25.4 (6.8)
SNRI			0.066
No	61	32.0 (10.7)
Yes	20	27.1 (9.4)
Subjective global assessment			0.36
A Not malnourished	75	31.1 (10.7)
B Moderately malnourished	6	27.0 (8.0)
BMI, kg/m²	81	0.11^†	0.32
Age, years	81	0.15^†	0.19

†

Correlation coefficient.

FACIT-Fatigue: functional assessment of chronic illness therapy fatigue scale; BMI: body mass index; NSAIDs: non-steroidal anti-inflammatory drugs; SSRI: selective serotonin reuptake inhibitor; SNRI: serotonin and norepinephrine reuptake inhibitor; SD: standard deviation.

There was no statistically significant difference between the SF-36 domain scores of iron and non-iron deficient patients (Table 3). Multiple patient characteristics were associated with SF-36 domains (see Supplementary Table 1 available online). Agents for neuropathic pain were associated with decreased energy and emotional wellbeing. Psychotropics were associated with role limitations due to emotional problems, poorer emotional wellbeing and social functioning. Serotonin-norepinephrine reuptake inhibitor (SNRI) usage was associated with role limitations due to physical and emotional problems, poorer emotional wellbeing and decreased general health. Medications that affect coagulation were linked to poorer physical functioning and energy. Various domains were significantly associated with substance abuse, central nervous system comorbidity, deep vein thrombosis comorbidity, medications that possibly affect coagulation, selective serotonin reuptake inhibitors (SSRIs) and subjective global assessment, although most had small group sizes and should be interpreted with caution.

Table 3.

Association between iron deficiency and SF-36 domains.

	Not iron deficient (n = 33)	Iron deficient (n = 47)
SF-36 domain	Median (IQR)	Median (IQR)	P value
Physical functioning	55 (25–75)	45 (30–70)	0.88
Role limitations—physical health	25 (0–50)	0 (0–50)	0.41
Role limitations—emotional problems	33.3 (0–66.7)	33.3 (0–100)	0.41
Energy/fatigue	45 (30–55)	45 (30–55)	0.91
Emotional wellbeing	68 (52–76)	64 (48–80)	0.69
Social functioning	50 (37.5–75)	50 (37.5–75)	0.48
Pain	32.5 (22.5–45)	22.5 (12.5–45)	0.10
General health	55 (30–70)	45 (35–70)	0.59

IQR: interquartile range; SF-36: 36-item short form survey of health-related quality of life.

Overall, this patient group had the poorest quality of life in the domain of role limitations due to physical health (median 0, IQR 0–50), followed by pain (median 22.5, IQR 22.5–45). There was no statistically significant difference in domain scores between male and female patients. There was a weak relationship between increasing age and decreasing physical functioning (r −0.22, P = 0.044), and a weakly positive relationship between increasing age and energy (r 0.26, P = 0.018).

Discussion

There was a substantial proportion of patients with ID (58.8%) in this sample of chronic pain patients. There was no significant difference found in the FACIT-Fatigue score between iron deficient and non-iron deficient groups. Overall, there was a high burden of fatigue (mean FACIT-Fatigue 30.8) in this group. We were unable to compare fatigue scores between iron deficient patients without anaemia and those with IDA due to the low percentage of anaemic patients. Health-related quality of life as measured by SF-36 domain scores was not significantly diminished in iron deficient patients. There was no significant relationship between SF-36 pain scores and ID, although the median score was lower in the ID group.

The study by Ahmed et al. of iron status in Australian adults reported an ID prevalence of 20.3% of pre-menopausal women, 5% of women 50 years or older, and 1.5% of men.³ It should be noted that there is significant variation in the diagnostic criteria of ID, with Ahmed et al. employing a definition of serum ferritin less than 20 μg/l. The prevalence of IDA (2.5%) in our study was low and is likely to be related to the smaller proportion of pre-menopausal women in this sample.

There have been limited studies examining the relationship between pain and ID in selected chronic pain conditions including fibromyalgia and migraine. Ortancil et al. hypothesised that ID may play a role in the pathophysiology of fibromyalgia as iron is essential for the formation of neurotransmitters such as dopamine, which have been found to be of a lower concentration in the cerebrospinal fluid of patients with fibromyalgia.²⁷ The aetiology of chronic pain is diverse in the patients presenting to chronic pain clinics. Our sample included only two patients with fibromyalgia and two with migraine. Further research into the role of ID in the pathophysiology of these conditions may lead to targeted treatment options in the future.

SF-36 scores in domains related to emotional wellbeing were lower in patients using SNRIs, psychotropic drugs and medications to manage neuropathic pain. Identification of patients in these groups may allow for focused treatment in chronic pain clinics.

The main limitations of this study were the small sample size and lack of a healthy population control group. The cohort was heterogeneous in terms of the aetiology of their chronic pain. Due to the small sample size, multivariable modelling was not performed to investigate further the independent effect of iron deficiency on SF-36 and FACIT-Fatigue. At the univariable level, some variables had small group sizes and should be interpreted with caution. While multiple factors were associated with SF-36 domains, many groups had small sizes requiring caution in their interpretation. As this was a cross-sectional study, we did not measure the effect of iron replacement therapy. Serum ferritin is frequently used as a single measure of iron status but is only an estimation of iron status, given it may be raised in conditions such as inflammation, malignancy and increased alcohol intake. FACIT-Fatigue and SF-36 scores were not compared with norms for the Australian general population.

Conclusion

Only 2.5% of the study population had IDA, but there was a high prevalence of iron deficiency without anaemia in patients presenting to this chronic pain clinic. There was no statistically significant difference in FACIT-Fatigue or SF-36 scores between the iron deficient and non-iron deficient groups. However, there was a high burden of fatigue overall in our study population. The data collected from this study may help inform the evaluation of treatment at chronic pain clinics using patient-reported health-related outcome measures and iron supplementation in the future.

Supplemental Material

sj-pdf-1-aic-10.1177_0310057X241263612 - Supplemental material for A cross-sectional study of the relationship between iron deficiency anaemia and chronic pain

Supplemental material, sj-pdf-1-aic-10.1177_0310057X241263612 for A cross-sectional study of the relationship between iron deficiency anaemia and chronic pain by Kerstin H Wyssusek, Christine AWoods, Emily T Minard, Julie Lee, Anita Pelecanos and Paul Gray in Anaesthesia and Intensive Care

Footnotes

Author contribution(s)

Kerstin H Wyssusek: Conceptualization; Data curation; Funding acquisition; Methodology; Supervision; Writing – review & editing.

Christine A Woods: Data curation; Methodology; Project administration; Supervision; Writing – review & editing.

Emily T Minard: Formal analysis; Writing – original draft; Writing – review & editing.

Julie Lee: Formal analysis; Writing – original draft; Writing – review & editing.

Anita Pelecanos: Formal analysis; Writing – original draft; Writing – review & editing.

Paul Gray: Formal analysis; Writing – original draft; Writing – review & editing.

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

ORCID iD

Emily T Minard

Supplemental material

Supplemental material for this article is available online.

References

World Health Organization. The global prevalence of anaemia in 2011. Geneva: World Health Organization, 2015. https://apps.who.int/iris/handle/10665/177094 (accessed January 2022).

Safiri

Kolahi

A-A

Noori

, et al. Burden of anemia and its underlying causes in 204 countries and territories, 1990–2019: results from the Global Burden of Disease Study 2019. J Hematol Oncol 2021; 14: 185. doi:10.1186/s13045-021-01202-2

Ahmed

Coyne

Dobson

, et al. Iron status among Australian adults: findings of a population based study in Queensland, Australia. Asia Pacific J Clin Nutr 2008; 17: 40–47.

Mistry

Hosoya

Kohut

, et al. Iron deficiency in heart failure, an underdiagnosed and undertreated condition during hospitalization. Ann Hematol 2019; 98: 2293–2297. doi:10.1007/s00277-019-03777-w

Gisbert

Gomollon

Common misconceptions in the diagnosis and management of anemia in inflammatory bowel disease. Am J Gastroenterol 2008; 103: 1299–1307. doi:10.1111/j.1572-0241.2008.01846.x

Rasu

Manley

Crawford

, et al. Undertreatment of anemia in patients with chronic kidney disease in the United States: analysis of national outpatient survey data. Clin Ther 2007; 29: 1524–1534. doi:10.1016/j.clinthera.2007.07.016

Ekiz

Agaoglu

Karakas

, et al. The effect of iron deficiency anemia on the function of the immune system. Hematol J 2005; 5: 579–583. doi:10.1038/sj.thj.6200574

Hassan

Badr

Karam

, et al. Impact of iron deficiency anemia on the function of the immune system in children. Medicine 2016; 95: e5395–e. doi:10.1097/MD.0000000000005395

Haas

Brownlie

IV.

Iron deficiency and reduced work capacity: a critical review of the research to determine a causal relationship. J Nutr 2001; 131: 676S–690S. doi:10.1093/jn/131.2.676S

10.

Groner

Holtzman

Charney

, et al. A randomized trial of oral iron on tests of short-term memory and attention span in young pregnant women. J Adolesc Health Care 1986; 7: 44–48. doi:10.1016/s0197-0070(86)80094-8

11.

Bruner

Joffe

Duggan

, et al. Randomised study of cognitive effects of iron supplementation in non-anaemic iron-deficient adolescent girls. Lancet 1996; 348: 992–996. doi:10.1016/S0140-6736(96)02341-0

12.

Murray-Kolb

Beard

JL.

Iron treatment normalizes cognitive functioning in young women. Am J Clin Nutr 2007; 85: 778–787. doi:10.1093/ajcn/85.3.778

13.

Krayenbuehl

Battegay

Breymann

, et al. Intravenous iron for the treatment of fatigue in nonanemic, premenopausal women with low serum ferritin concentration. Blood 2011; 118: 3222–3227. doi:10.1182/blood-2011-04-346304

14.

Verdon

Burnand

Stubi

, et al. Iron supplementation for unexplained fatigue in non-anaemic women: double blind randomised placebo controlled trial. BMJ 2003; 326: 1124. doi:10.1136/bmj.326.7399.1124

15.

Favrat

Balck

Breymann

, et al. Evaluation of a single dose of ferric carboxymaltose in fatigued, iron-deficient women—PREFER a randomized, placebo-controlled study. PloS One 2014; 9: e94217. doi:10.1371/journal.pone.0094217

16.

Benoliel

Svensson

Evers

, et al. The IASP classification of chronic pain for ICD-11: chronic secondary headache or orofacial pain. Pain 2019; 160: 60–68. doi:10.1097/j.pain.0000000000001435

17.

Blyth

March

Brnabic

AJM

, et al. Chronic pain in Australia: a prevalence study. Pain 2001; 89: 127–134. doi:10.1016/s0304-3959(00)00355-9

18.

Breivik

Collett

Ventafridda

, et al. Survey of chronic pain in Europe: prevalence, impact on daily life, and treatment. Eur J Pain (London, England) 2006; 10: 287–333. doi:10.1016/j.ejpain.2005.06.009

19.

Dahlhamer

Lucas

Zelaya

, et al. Prevalence of chronic pain and high-impact chronic pain among adults – United States, 2016. MMWR Morb Mortal Wkly Rep 2018; 67: 1001–1006. doi:10.15585/mmwr.mm6736a2

20.

Fishbain

Cutler

Rosomoff

, et al. Chronic pain-associated depression: antecedent or consequence of chronic pain? a review. Clin J Pain 1997; 13: 116–137. doi:10.1097/00002508-199706000-00006

21.

Covington

EC.

Depression and chronic fatigue in the patient with chronic pain. Primary Care 1991; 18: 341–358.

22.

Becker

Bondegaard Thomsen

, et al. Pain epidemiology and health related quality of life in chronic non-malignant pain patients referred to a Danish multidisciplinary pain center. Pain 1997; 73: 393–400. doi:10.1016/S0304-3959(97)00126-7

23.

Kewman

Vaishampayan

Zald

, et al. Cognitive impairment in musculoskeletal pain patients. Int J Psychiatry Med 1991; 21: 253–262. doi:10.2190/FRYK-TMGA-AULW-BM5G

24.

Grigsby

Rosenberg

Busenbark

Chronic pain is associated with deficits in information processing. Percept Motor Skills 1995; 81: 403–410. doi:10.2466/pms.1995.81.2.403

25.

Dick

Eccleston

Crombez

Attentional functioning in fibromyalgia, rheumatoid arthritis, and musculoskeletal pain patients. Arthr Rheum 2002; 47: 639–644. doi:10.1002/art.10800

26.

Creavin

Dunn

Mallen

, et al. Co-occurrence and associations of pain and fatigue in a community sample of Dutch adults. Eur J Pain (London, England) 2010; 14: 327–334. doi:10.1016/j.ejpain.2009.05.010

27.

Ortancil

Sanli

Eryuksel

, et al. Association between serum ferritin level and fibromyalgia syndrome. Eur J Clin Nutr 2010; 64: 308–312. doi:10.1038/ejcn.2009.149

28.

Legangneux

Mora

Spreux-Varoquaux

, et al. Cerebrospinal fluid biogenic amine metabolites, plasma-rich platelet serotonin and [3H]imipramine reuptake in the primary fibromyalgia syndrome. Rheumatol (Oxford) 2001; 40: 290–296. doi:10.1093/rheumatology/40.3.290

29.

Boomershine

Koch

Morris

A blinded, randomized, placebo-controlled study to investigate the efficacy and safety of ferric carboxymaltose in iron-deficient patients with fibromyalgia. Rheumatol Ther 2018; 5: 271–281. doi:10.1007/s40744-017-0088-9

30.

Pamuk

Set

, et al. An increased prevalence of fibromyalgia in iron deficiency anemia and thalassemia minor and associated factors. Clin Rheumatol 2008; 27: 1103–1108. doi:10.1007/s10067-008-0871-7

31.

Okan

Cagliyan Turk

Sivgin

, et al. Association of ferritin levels with depression, anxiety, sleep quality, and physical functioning in patients with fibromyalgia syndrome: a cross-sectional study. Croat Med J 2019; 60: 515–520. doi:10.3325/cmj.2019.60.515

32.

Mader

Koton

Buskila

, et al. Serum iron and iron stores in non-anemic patients with fibromyalgia. Clin Rheumatol 2012; 31: 595–599. doi:10.1007/s10067-011-1888-x

33.

Tayyebi

Poursadeghfard

Nazeri

, et al. Is there any correlation between migraine attacks and iron deficiency anemia? A case-control study. Int J Hematol-Oncol Stem Cell Res 2019; 13: 164–171.

34.

Gur-Ozmen

Karahan-Ozcan

Iron deficiency anemia is associated with menstrual migraine: a case-control study. Pain Med (Malden, Mass) 2016; 17: 596–605. doi:10.1093/pm/pnv029

35.

Pamuk

Top

Uyanik

, et al. Is iron-deficiency anemia associated with migraine? Is there a role for anxiety and depression? Wiener Klin Wochenschr 2016; 128(Suppl. 8): 576–580. doi: 10.1007/s00508-015-0740-8

36.

Vukovic-Cvetkovic

Plavec

Lovrencic-Huzjan

, et al. Is iron deficiency anemia related to menstrual migraine? Post hoc analysis of an observational study evaluating clinical characteristics of patients with menstrual migraine. Acta Clin Croatica 2010; 49: 389–394.

37.

Wilkes

Castro

Mohan

, et al. Health status of patients with chronic pain attending a pain center. Pain Manage Nurs: Official Journal of the American Society of Pain Management Nurses 2003; 4: 70–76. doi:10.1016/s1524-9042(02)54208-9

38.

Becker

Sjogren

Bech

, et al. Treatment outcome of chronic non-malignant pain patients managed in a Danish multidisciplinary pain centre compared to general practice: a randomised controlled trial. Pain 2000; 84: 203–211. doi:10.1016/s0304-3959(99)00209-2

39.

Bergman

Jacobsson

Herrström

, et al. Health status as measured by SF-36 reflects changes and predicts outcome in chronic musculoskeletal pain: a 3-year follow up study in the general population. Pain 2004; 108: 115–123. doi:10.1016/j.pain.2003.12.013

40.

Harris

Taylor

Thielke

, et al. Research electronic data capture (REDCap)—a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform 2009; 42: 377–381. doi:10.1016/j.jbi.2008.08.010

41.

Acaster

Dickerhoof

DeBusk

, et al. Qualitative and quantitative validation of the FACIT-fatigue scale in iron deficiency anemia. Health Qual Life Outcomes 2015; 13: 60. doi:10.1186/s12955-015-0257-x

42.

Cella

Yount

Sorensen

, et al. Validation of the functional assessment of chronic illness therapy fatigue scale relative to other instrumentation in patients with rheumatoid arthritis. J Rheumatol 2005; 32: 811–819.

43.

Lai

Beaumont

Ogale

, et al. Validation of the functional assessment of chronic illness therapy-fatigue scale in patients with moderately to severely active systemic lupus erythematosus, participating in a clinical trial. J Rheumatol 2011; 38: 672–679. doi:10.3899/jrheum.100799

44.

Elliott

Smith

Hannaford

, et al. The course of chronic pain in the community: results of a 4-year follow-up study. Pain 2002; 99: 299–307. doi:10.1016/s0304-3959(02)00138-0

45.

Elliott

Renier

Palcher

JA.

Chronic pain, depression, and quality of life: correlations and predictive value of the SF-36. Pain Med (Malden, Mass) 2003; 4: 331–339. doi:10.1111/j.1526-4637.2003.03040.x

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