From speaking with our community of practitioners, we learnt that many wanted handy reference guides to summarise advanced testing options for key health conditions.
In light of this, our Clinical Support Specialist, Virginia Blake, has written a clinically robust introduction to advanced testing options for Fibromyalgia.
Read and bookmark this page if you need a starting point for advanced testing options for Fibromyalgia.
What is Fibromyalgia?
Fibromyalgia (FM) is a condition characterised by chronic, widespread musculoskeletal pain and increased tenderness on specific soft tissue areas (Goldenberg, 2009). It is frequently seen with fatigue, headaches, sleep disturbance, cognitive dysfunction and depression / anxiety (Chen & McKenzie-Brown, 2015).
There is significant overlap with Chronic Fatigue Syndrome (CFS) (Teitelbaum et al., 2020) and with major mood disorder and depression (Arnold et al., 2004). It is frequently present with other syndromes with similar symptoms e.g. rheumatological conditions and can co-exist with irritable bowel syndrome (Mezhov et al., 2021).
Brief History
FM was first clinically described in the mid 19th century. “Fibrositis” was coined by Sir William Gowers in 1904 when he was actually describing regional pain syndrome. Subsequent work showed that inflammation was not present in the connective tissues and the name was considered a misnomer. The term “Fibromyalgia” was first introduced in 1976 by the American Rheumatism Association. Derived from Latin and Greek, it translates as pain in the muscle and fibrous tissues (Chong & Ng, 2009).
Epidemiology
Prevalence of fibromyalgia is approximately 2-4% of the general population. With age adjustment, this is around 7 cases per 1000 males and 11 cases per 1000 females. Prevalence rate in children is 1.2 to 1.4%.Most studies show greater incidence in female populations with a female to male ratio of approximately 7-9:1 (Chen & McKenzie-Brown, 2015). But this gender bias may be dependent on assessment methods used (Arout et al., 2018).
Some researchers suggest incidence may be higher and / or increasing based on a European survey in 5 countries, which found an incidence of 4-7% in the general population (Branco et al., 2010). Development of fibromyalgia is most common aged 20 to 50 years. It is found in around 5-6% of adults presenting at general medical clinics while in rheumatology clinics, it accounts for 12 to 30% of new patients (Chong & Ng, 2009).
Classification
The diagnostic criteria for fibromyalgia are based on the recommendations of the American College of Rheumatology (ACR) 2010 (Wolfe et al., 2010). A patient satisfies diagnostic criteria for fibromyalgia if the following 3 conditions are met:
- Widespread pain index (WPI) 7 and symptom severity (SS) scale score 5 or WPI 3–6 and SS scale score 9.
- Symptoms have been present at a similar level for at least 3 months.
- The patient does not have a disorder that would otherwise explain the pain.
These recommendations were developed as there is no laboratory diagnostic test for fibromyalgia. It is worth bearing in mind that they are not necessarily helpful for individual patient diagnosis (Goldenberg, 2009) but as yet, no other classification system has been decided upon. Recently the Royal College of Physicians reviewed and updated UK clinical guidelines but diagnosis is still based on the ACR criteria above (Royal College of Physicians., 2022).
Differential Diagnosis
As the symptoms of FM are so varied and diffuse and may also co-exist with other conditions; differential diagnosis is complex and may have been a lengthy process for your client. Another issue to be aware of is that FM, as a condition in it’s own right, can also be present along with other conditions. By the time your client has come to you, the following should have been assessed (Goldenberg, 2009):
- Autoimmune / autoinflammatory diseases such as rheumatoid arthritis, systemic lupus erythemotosus, ankolysing spondulitis, polymyalgia rheumatica, myositis myopathies
- Chronic fatigue syndrome
- Myofascial pain syndrome
- Hypothyroid (which may be autoimmune)
- Certain cancers
Aetiology
It is not clear why fibromyalgia develops. A number of different mechanisms have been suggested. As the presenting symptoms can differ so widely, some propose that there may not be one causative factor (Hechtman, p.626 2019). I will explore current theories on aetiology in the hope that it will support your work to develop an individual approach with the clients you see in clinic. Based on current experience, I agree that the causes of symptoms do vary from client to client and there is no one causative agent.
Central Nervous System Differences: Dysfunction of the central nervous system (CNS) is an important aspect of FM. Changes to the spinal and cerebral cortex processing of pain results in allodynia (pain in response to non-painful stimuli) and hyperalgesia (excess pain in response to normally painful stimulus). This is described as ‘central sensitisation’ (Hechtman,p.627 2019). There can also be hypersensitivity to sound, light, smell and taste (‘central sensitivity syndromes’) (Mezhov et al., 2021).
Altered Neurotransmitters: Both opioid signalling and changes to serotonin production, signalling and levels have been found in fibromyalgia. Analysis of cerebrospinal fluid (CSF) in patients with FM compared to controls suggest there may be increased opioid and reduced serotonin metabolism. This is likely to lead to low mood and increased pain, as serotonin amplifies the pain controlling effects of opiates (Tour et al., 2022). These changes could be caused by alterations in brain centres, the spinal chord and the dorsal horn, triggering a hypersensitive CNS (Mezhov et al., 2021). It is not clear what causes these changes. Dopamine is also implicated, with receptor function changes and reduced dopamine levels observed. As dopamine plays a central role in pain perception and pain relief it most likely contributes to the pain and reduced feelings of well-being found in fibromyalgia. (Hechtman p627, 2019). This dysregulation is hypothesised to lead to an increased level of excitatory neurotransmitters, such as substance P and glutamate (Yepez et al., 2022). Substance P is a neuropeptide involved in transmitting pain signals from the periphery to the CNS and has been found to be elevated in the CSF of those with FM (Zhang et al., 2016)
HPA Axis Dysregulation: Dysregulation of the HPA axis has been found in patients with fibromyalgia and this may also contribute to symptoms. Main findings are changes in the diurnal pattern of cortisol secretion, with some patients showing hypo and others hypercortisolism (Yepez et al., 2022; Carvalho et al., 2008).
Immune Dysregulation: Some studies have shown that there are increased levels of proinflammatory cytokines and activated T cells, while others show no changes in immune cells (Carvalho et al., 2008). At this stage, the research is unclear, but for some with FM, immune dysregulation may play a role. This could be secondary to altered secretion of cortisol or it could be a primary cause; as a result of infection
Infection: Viral and bacterial infection are potentially linked to FM, with some studies showing an association with hepatitis B (Ozsahin et al., 2013) and C (Buskila, 1997); Lyme disease, mycoplasma and HIV (Branco et al., 2010). Increased incidence of Human herpes virus-6 (HHV-6) and human herpes virus-7 (HHV-7) have been found in FM patients (n=43, control n=50) with a statistically significant correlation with HHV-6 and not HHV-7 (Krumina et al., 2019). Some older studies have shown a link with EBV (Buchwald et al., 1987).
Gender / hormones: Most patients diagnosed with FM are women (Yepez et al., 2022). Those with FM are reported to be between twice to 9 times more likely to be female. However, since the dependence on ‘tender points’, which are more common in women, for diagnosis was removed from the assessment criteria in 2010, some studies since indicated parity between genders while others have suggested a ratio of 3:1 skewing female (Arout et al., 2018). Specific findings on the relationship between FM and the sex hormones have looked at the relationship between pain and menstrual cycle and menopause. The results are conflicting. Pamuk & Cakir (2005) did find that half of their FM subjects (n=152) noted an increase in pain with menses and menopause, with no impact for the other half. Blood hormone levels were not measured and assessment was based on subjective methodology. In a more rigourously designed study of menstruating women with healthy control group of equal size (n=74 each group), no relationship between serum assessed sex hormones and pain were found. Ovulation was determined by 9-day urine testing (Okifuji & Turk, 2006). In practice, I have found a worsening of symptoms in perimenopause and menopause, particularly if associated with CFS.
Fibromyalgia and Functional Gut Disorders: A systematic review of 14 studies of n=1340 adults with FM and n=363 healthy controls found that IBS is more common in FM. The authors note that amelioration of gastrointestinal symptoms correlate with improved symptomatology of FM. Other functional gut disorders are not as well studied. They conclude that further study of gastrointestinal disorder in FM is warranted (Erdrich et al., 2020a). The same group also systematically reviewed research on gastrointestinal biomarkers and the microbiome in FM. Despite limited research, they conclude that there is sufficient evidence to suggest that the composition of the gastrointestinal microbiome may be associated with FM (Erdrich et al., 2020b). While no single gut marker has been validated for FM, infections to evaluate include Helicobacter pylori, Yersinia enterocolitica, Campylobacter jejuni. Dysbiosis to consider: raised Parabacteroides and Akkermansia muciniphila, potentially leading to increases in GABA and glutamate. Stool chemistries showed conflicting results, with higher and lower levels of butyrate found in FM (Erdrich et al., 2020b). Small intestinal bacterial overgrowth was found in 100% of subjects with FM by Pimentel (2004) However, the study has significant limitations. For reasons unclear, only hydrogen results were reported on and not methane. Criteria for the diagnosis of FM were also unclear. In study of 1100 IBS patients between 2011-2019, Berstad et al., (2020) found that 80% of IBS patients had musculoskeletal pain and 87% had CFS. Again however, criteria for diagnosis of FM was not clear. They hypothesised that IBS as a result of dysbiosis, that worsened over time was a cause of muscuoloskeletal pain. They suggest that early and /or frequent antibiotic use depletes Lactobacilli resulting in SIBO and/or the development of the invasive hyphal form of Candida ablicans. They coin this the ‘Dysbiotic March Hypothesis’. And that immune changes as a result of this dysbiotic march contribute to the development of pain syndromes.
Thyroid Function: In a systematic review and meta-analysis of 10 original studies and 5 case control studies, thyroid autoantibodies were more than 3 times more likely to be found in FM patients compared to healthy controls. This was increased in FM patients who were also menopausal. The authors recommend assessment of thyroid autoimmune status in all FM patients (Park et al., 2021).
Genetic links: Family based studies and twin studies have suggested a genetic ink in FM. First degree relatives of those with FM risk of developing FM was 8.5 times the risk in the general population (Arnold et al., 2004). In the Finnish Twin Cohort study (n=12,502; with n=49 diagnosed with FM) found that heritability was estimated to be 51% (Markkula et al., 2009).
Stress and Trauma Stress and trauma are thought to be significant contributors to onset and worsening of FM. Some stressors that are considered capable of triggering FM include (Clauw, 2009):
- Physical trauma (e.g. car accidents)
- Psychological trauma
- Hormonal changes (e.g. hypothyroid)
- Peripheral pain syndromes
Mitochondria:There is evidence of mitochondrial dysfunction in FM, but argument remains as to whether it is cause or effect. In study using microdialysis and MRI of FM patients (n=33 control n=31)(Gerdle et al., 2020) found that there were increased concentrations of lactate and pyruvate and lower levels of ATP and phosphocreatine (PCr) in muscle tissue in the FM cohort. Lactate can be transferred into the mitochondria and converted to pyruvate, then converted to Acetyl CoA for oxidative phosphorylation in the citric acid cycle. In FM the higher concentrations of lactate and pyruvate and lower concentrations of ATP and PCr in muscle tissue suggest mitochondrial dysfunction. Gerdle et al. (2020) posit that this mitochondrial dysfunction is secondary to oxidative stress caused by adverse environmental factors.
Nutritional Deficiencies: Research on deficiency and supplementation of micronutrients in FM is inconclusive and contradictory. However, measuring vitamin D, vitamin A and C, B vitamins, magnesium and E, beta-carotene may be useful as they have found to be deficient in some cases of FM (Pagliai et al., 2020) and intervention studies for vitamin D, magnesium and vitamin C show some benefit with supplementation (Bjørklund et al., 2018). Most studies on supplementation (in any condition) do not measure baseline levels of micronutrients. So, it is rarely clear that there was deficiency and supplementation helped. If no baseline measurements are taken, one may suggest that often supplemented micronutrients are used where there is no clinical need. This absence of baseline testing is a major flaw in many nutrition supplementation intervention studies.
Heavy Metals: Higher concentrations of heavy metals such as cadmium, lead and mercury have been found in some patients with FM (Bjørklund et al., 2018).
Mycotoxins: There is limited research in this area, but case reports, grey literature (Gray n.d.) and studies using CFS patients as the investigated population do indicate that mycotoxins should be assessed in FM. A Finnish study on hospital workers exposed to water damaged buildings (n=90, control=45) with a high incidence of CNS and PNS symptoms investigated the link with FM. Musculoskeletal symptoms were a primary variable. In the test cohort, 51% had musculoskeletal pain compared to 22% in the control group (p<0.02). Interestingly, 62% of exposed cohort also had CNS symptoms compared to 11% of the control group (p<0.001) and the authors conclude that exposure to mycotoxins should be considered as a causative factor in these conditions (Hyvönen et al., 2020). In a study testing for mycotoxins in a CFS population, researchers found that those with CFS and FM were more likely to have mycotoxin exposure (n=112, control =55) 93% of the CFS group had one or more mycotoxins with 0% of the control group testing positive (p<0.001) (Brewer et al., 2013)
Multiple Chemical Sensitivities: There is limited evidence, but worth considering levels of toxic exposure and innate capacity to clear it (Hu & Baines, 2018).
Recommended Testing
As you can see, the potential contributing factors to FM are wide and varied. As such, an individual approach for your client needs to be developed based on detailed case taking. I broken the tests down into categories:
General Overview
Functional Platinum Panel by Medical Diagnosis
The Functional Platinum Panel provides a comprehensive insight into these key health areas: full blood count, biochemistry, endocrinology, haematology, and immunology. This an excellent all-round test, alongside areas listed above, it also assesses vitamin B12, calcium, iron including ferritin and TIBC, folate and homocysteine. Thyroperoxidase and thyroglobulin antibodies are included.
Organic Acid Test (OAT) by Great Plains Laboratory
An evaluation of 76 biomarkers provides a comprehensive metabolic snapshot of overall health, including intestinal microbial overgrowth (yeast and bacteria), mitochondrial health, neurotransmitter status, detox capacity, oxidative stress, markers for vitamin and mineral levels and oxalates.
This is another big picture test, particularly relevant in fibromyalgia as it can give an overview of system health. Detoxification capacity may be affected in FM. Microbial overgrowth may be a contributing factor (yeast and bacteria). By examining the mitochondrial metabolites measured, the presence of excess toxins and toxicants can be deduced. High oxalate levels may be contributing to pain. You will find useful information on nutrient needs. This test is not too difficult for a client to do and gives an indication of which system may be under pressure and direction on where to go next.. It is a great place to start if you are not sure where to begin.
Central Nervous System, Neurotransmitters, and HPA Axis Dysregulation
DUTCH Complete by Precision Analytical:
DUTCH Complete comprehensively assesses sex and adrenal hormones, including oestrogen, progesterone, testosterone, DHEA and cortisol, and their metabolites. It also measures daily free cortisol and cortisone patterns, the oxidative stress marker 8-OHdG, melatonin and nine organic acids, including markers for vitamin B12 (methylmalonate), vitamin B6 (kynurenate and xanthurenate), biotin (β-hydroxyisovalerate), glutathione (pyroglutamate), dopamine (homovanillate), norepinephrine / epinephrine (vanilmandelate), neuroinflammation (quinolinate) and tryptophan putrefaction (indican). The DUTH Plus is the DUTCH Complete above, with additional assessment of the cortisol awakening response (CAR) which can be used to evaluate HPA-axis function further.
HuMap (Hormone & Urinary Metabolites Assessment Profile) by Doctor’s Data
HuMap provides a comprehensive overview of steroid hormones, including oestrogen, progesterone, testosterone, DHEA and cortisol, an extensive evaluation of their metabolites and the efficiency of the enzymes that metabolise these hormones. This non-invasive test requires only 4 or 5 separate urine collections. Because the breakdown of hormones relies so heavily on processes within the liver, this test can also elucidate areas of interest about the conjugation of each metabolite. Additionally, testing urinary hormone metabolites can contribute to further understanding endogenous hormone secretion, supplemental hormone utilisation, enzyme activity, oxidative stress, and insight into how your body metabolises hormones.
Doctor’s Data also provide additional urine panels, including Estrogen Metabolites Profile, Sex Hormones Profile, Adrenal Corticoids Profile and Androgens and Progesterone Profile when targeted information is required or for retesting.
Saliva hormone and adrenal panels are also available to help understand the active, bioavailable, and unbound portion of sex steroid hormones and assess the therapeutic response to hormone replacement.
NeuroBasic Profile by Doctor’s Data
NeuroBasic Profile is a non-invasive urinary profile to assess the body's ability to make and break down neurotransmitters (Dopamine, Serotonin, 5HIAA, GABA, Glutamate, Glycine, Epi, NorEpi, Epi: NorEPi ratio, Histamine, PEA) and is representative of the whole body's neurotransmitter levels.
Comprehensive Neurotransmitter Profile by Doctor’s Data:
This extension of the NeuroBasic provides a more detailed assessment of neurotransmitter function and includes metabolites to help understand nutritional cofactor need and expression of nutrigenetics. NeuroBasic or Comprehensive Neurotransmitter Profile work well with hormone testing and can be ordered as an add-on to HuMap panels at a reduced cost.
Immune Status
Cyrex Laboratories
Regenerus is the UK, Ireland and Europe representative for Cyrex Laboratories. Cyrex is a clinical immunology laboratory specialising in functional immunology and autoimmunity. They focus on assessing, understanding, and educating practitioners on environmentally induced autoimmunity. Cyrex Labs offer 18 arrays using their proprietary, patented laboratory techniques.
Popular panels include, but are not limited to:
- Array 10 Foods, general
- Array 3 Gluten
- Array 4 Non-gluten Cross-reactive Foods and Dairy
- Array 5 Multiple Autoimmune Reactivity Screen
- Array 11 Chemical Immune Reactivity Screen
- Array 12 Pathogen Associated Immune Reactivity
- Array 14 Mucosal Immune Reactivity Screen (saliva)
- Alzheimer’s LINX
Autoimmune Trio (Viral Panel) by Immunosciences Lab:
Three viruses, in particular, have been identified as the major players and contributors to inflammation and autoimmune disorders: severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Epstein-Barr virus (EBV), and human herpesvirus 6 (HHV-6). Autoimmune Viral Trio panel detects the possible role of three viruses in a variety of inflammatory and autoimmune disorders, including Long COVID, SARS-CoV-2, Epstein-Barr Virus and Human Herpes Type 6.
Lyme Panel B by Immunosciences Lab
Lyme-specific antibodies, Borrelia subspecies antibodies, Lyme co-infection and Western blot assay. Lyme infection has been associated with FM.
The Gut
GI360 Complete, add on H. Pylori by Doctor’s Data
Although the research is limited, there are indications that the gut microbiome is altered in FM. This test assesses Yersinia enterocolitica, Campylobacter jejuni, Parabacteroides and Akkermansia muciniphila, correlated with FM in the research. Add on H.pylori for the complete picture. There is also the Comprehensive Stool Analysis with PCR+ Parasitology, which includes various smaller panels for retesting specific areas of concern.
SIBO Glucose by Breath Trackers
Hydrogen, methane, and combined gases to assess small intestinal bacterial overgrowth using glucose substrate
SIBO Lactulose by Breath Tracker
Hydrogen, methane, and combined gases to assess small intestinal bacterial overgrowth using lactulose substrate. Limited research in SIBO and FM, but if symptom picture fits, assess. If budget allows, run alongside OAT to test SIFO.
Thyroid
Thyroid Complete by Medical Diagnosis
Thyroid Complete includes TSH, T4, T3, fT4, fT3, TPO Ab, TG Ab, T-uptake and rT3, serving as a valuable tool for detecting those patients that are suffering from thyroid dysfunction, including low-grade hyper- or hypothyroidism, which might otherwise go undetected through standard blood tests, and auto-immune thyroid conditions either Hashimoto’s disease or Graves’ disease. NB, other panels are available, including Thyroid Basic, Thyroid Basic Plus and Thyroid Advanced.
To learn more about the Thyroid Complete, click here.
Essential Vitamin Profile by Lab4More
Measuring vitamin D, vitamin A and C, B vitamins, magnesium and E, beta-carotene may be useful as they have found to be deficient in some cases of FM (Pagliai et al., 2020) and intervention studies for vitamin D, magnesium and vitamin C show some benefit with supplementation (Bjørklund et al., 2018).
This test can help you devise your micronutrient supplement plan.
- Zinc
- Vitamin E
- Vitamin D
- Vitamin B6
- Vitamin B2
- Vitamin B12
- Selenium
- Potassium
- Magnesium
- Iron
- Folic Acid
- Calcium
To learn more about the Essential Vitamin Profile, click here.
Hepatic Detox Profile by Doctor’s Data
An excellent tool for assessing phase 1 and 2 liver detoxification via measurement of D-glucaric acid and mercapturic acids, respectively.
To learn more about the Hepatic Detox Profile, click here.
GPL-Tox by Great Plains Laboratory
Provides assessment of exposure to 172 environmental pollutants and includes a marker for mutations of mitochondrial DNA. Multiple chemical sensitivity may be a factor for your client. This test examines the 172 most common and most deleterious to health environmental pollutants. This test is useful when you are not certain where toxicant exposure comes from. It can show up very interesting results in countryside dwellers and golfers.
To learn more about the GPL-TOX, click here.
MycoToxin by Great Plains Laboratory
Screens for seven mycotoxins and four mould species via LC-MS/MS. Mycotoxins can impact the immune system negatively and can be a missing link in a chronic health condition. It is worth doing as part of the Envirotox Complete Panel. See below. This is an excellent value package of 4 tests for the price of less than 2. In practice, I find a significant number of FM patients test positive for myctoxins.
To learn more about the MycoToxin, click here.
ENVIROtox Complete Panel byGreat Plains Laboratory
Combines Organic Acid Test (OAT), GPL-Tox, Mycotoxins and Glyphosate for a comprehensive environmental toxicity assessment. Higher concentrations of heavy metals such as cadmium, lead and mercury have been found in some patients with FM (Bjørklund et al., 2018).
To learn more about the ENVIROTox, click here.
Mercury Tri Test by Quicksilver Scientific
Assesses the body’s mercury overall burden and ability to detoxify and eliminate mercury.
Blood Metals Panel by Quicksilver Scientific
Screens for eight nutrient elements and seven toxic metals for indication of elevated exposure to toxic metals or imbalances of nutrient elements in whole blood.
References
ABLIN, J., SHOENFELD, Y., & BUSKILA, D. (2006). Fibromyalgia, infection and vaccination: Two more parts in the etiological puzzle. Journal of Autoimmunity, 27(3), 145–152. https://doi.org/10.1016/j.jaut.2006.09.004
Arnold, L. M., Hudson, J. I., Hess, E. V., Ware, A. E., Fritz, D. A., Auchenbach, M. B., Starck, L. O., & Keck, P. E. (2004). Family study of fibromyalgia. Arthritis & Rheumatism, 50(3), 944–952.
Arout, C. A., Sofuoglu, M., Bastian, L. A., & Rosenheck, R. A. (2018). Gender differences in the prevalence of fibromyalgia and in concomitant medical and psychiatric disorders: A National Veterans Health Administration Study. Journal of Women's Health, 27(8), 1035–1044. https://doi.org/10.1089/jwh.2017.6622
Berstad, A., Hauso, O., Berstad, K., & Berstad, J. E. R. (2020). From IBS to me – the dysbiotic march hypothesis. Medical Hypotheses, 140, 109648.
Buskila, D. (1997). Fibromyalgia in hepatitis C virus infection. Archives of Internal Medicine, 157(21), 2497. https://doi.org/10.1001/archinte.1997.00440420129014
Carvalho, L. S., Correa, H., Silva, G. C., Campos, F. S., Baião, F. R., Ribeiro, L. S., Faria, A. M., & D'Avila Reis, D. (2008). May genetic factors in fibromyalgia help to identify patients with differentially altered frequencies of immune cells? Clinical and Experimental Immunology, 154(3), 346–352.
Chong , Y. Y., & Ng, B. Y. (2009). Clinical aspects and management of fibromyalgia syndrome. Ann Acad Med Singapore., 38(11), 967–973.
Clauw, D. J. (2009). Fibromyalgia: An overview. The American Journal of Medicine, 122(12).
Hechtman, L. (2019). Musculoskeletal System. In Clinical naturopathic medicine (2nd ed., pp. 626–642)
Hu, H., & Baines, C. (2018). Recent insights into 3 underrecognized conditions: Myalgic encephalomyelitis-chronic fatigue syndrome, fibromyalgia, and environmental sensitivities-multiple chemical sensitivity. Can Fam Physician. 2018 Jun; 64(6): 413–415., 64(6), 413–415.
Pamuk , O. N., & Cakir, N. (2005). The variation in chronic widespread pain and other symptoms in fibromyalgia patients. The effects of menses and menopause. Clin Exp Rheumatol., 23(6), 778–882
Yepez, D., Grandes, X. A., Talanki Manjunatha, R., Habib, S., & Sangaraju, S. L. (2022). Fibromyalgia and depression: A literature review of their shared aspects. Cureus.
Zhang, H., Li, F., Li, W.-W., Stary, C., Clark, J. D., Xu, S., & Xiong, X. (2016). The inflammasome as a target for pain therapy. British Journal of Anaesthesia, 117(6), 693–707