chronic pain – Page 3 – American ME and CFS Society

Clinical Characteristics and Mechanisms of Musculoskeletal Pain in Long COVID

Abstract:

Objective: Musculoskeletal (MSK) pain is being increasingly reported by patients as one of the most common persistent symptoms in post-COVID-19 syndrome or Long COVID. However, there is a lack of understanding of its prevalence, characteristics, and underlying pathophysiological mechanisms. The objective of this review is to identify and describe the features and characteristics of MSK pain in Long COVID patients.

Methods: The narrative review involved a literature search of the following online databases: MEDLINE (OVID), EMBASE (OVID), CINAHL, PsyclNFO, and Web of Science (December 2019 to February 2022). We included observational studies that investigated the prevalence, characteristics, risk factors and mechanisms of MSK pain in Long COVID. After screening and reviewing the initial literature search results, a total of 35 studies were included in this review.

Results: The overall reported prevalence of MSK pain in Long COVID ranged widely from 0.3% to 65.2%. The pain has been reported to be localized to a particular region or generalized and widespread. No consistent pattern of progression of MSK pain symptoms over time was identified. Female gender and higher BMI could be potential risk factors for Long COVID MSK pain, but no clear association has been found with age and ethnicity. Different pathophysiological mechanisms have been hypothesized to contribute to MSK pain in Long COVID including increased production of proinflammatory cytokines, immune cell hyperactivation, direct viral entry of neurological and MSK system cells, and psychological factors.

Conclusion: MSK pain is one of the most common symptoms in Long COVID. Most of the current literature on Long COVID focuses on reporting the prevalence of persistent MSK pain. Studies describing the pain characteristics are scarce. The precise mechanism of MSK pain in Long COVID is yet to be investigated. Future research must explore the characteristics, risk factors, natural progression, and underlying mechanisms of MSK pain in Long COVID.

Source: Khoja O, Silva Passadouro B, Mulvey M, Delis I, Astill S, Tan AL, Sivan M. Clinical Characteristics and Mechanisms of Musculoskeletal Pain in Long COVID. J Pain Res. 2022 Jun 17;15:1729-1748. doi: 10.2147/JPR.S365026. PMID: 35747600; PMCID: PMC9212788. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9212788/ (Full text)

Sexual dimorphism in a neuronal mechanism of spinal hyperexcitability across rodent and human models of pathological pain

Abstract:

The prevalence and severity of many chronic pain syndromes differ across sex, and recent studies have identified differences in immune signalling within spinal nociceptive circuits as a potential mediator. Although it has been proposed that sex-specific pain mechanisms converge once they reach neurons within the superficial dorsal horn, direct investigations using rodent and human preclinical pain models have been lacking.

Here, we discovered that in the Freund’s adjuvant in vivo model of inflammatory pain, where both male and female rats display tactile allodynia, a pathological coupling between KCC2-dependent disinhibition and N-methyl-D-aspartate receptor (NMDAR) potentiation within superficial dorsal horn neurons was observed in male but not female rats. Unlike males, the neuroimmune mediator brain-derived neurotrophic factor (BDNF) failed to downregulate inhibitory signalling elements (KCC2 and STEP61) and upregulate excitatory elements (pFyn, GluN2B and pGluN2B) in female rats, resulting in no effect of ex vivo brain-derived neurotrophic factor on synaptic NMDAR responses in female lamina I neurons. Importantly, this sex difference in spinal pain processing was conserved from rodents to humans.

As in rodents, ex vivo spinal treatment with BDNF downregulated markers of disinhibition and upregulated markers of facilitated excitation in superficial dorsal horn neurons from male but not female human organ donors. Ovariectomy in female rats recapitulated the male pathological pain neuronal phenotype, with BDNF driving a coupling between disinhibition and NMDAR potentiation in adult lamina I neurons following the prepubescent elimination of sex hormones in females. This discovery of sexual dimorphism in a central neuronal mechanism of chronic pain across species provides a foundational step towards a better understanding and treatment for pain in both sexes.

Source: Dedek A, Xu J, Lorenzo LÉ, Godin AG, Kandegedara CM, Glavina G, Landrigan JA, Lombroso PJ, De Koninck Y, Tsai EC, Hildebrand ME. Sexual dimorphism in a neuronal mechanism of spinal hyperexcitability across rodent and human models of pathological pain. Brain. 2022 Apr 29;145(3):1124-1138. doi: 10.1093/brain/awab408. PMID: 35323848; PMCID: PMC9050559. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9050559/ (Full text)

Altered Pain in the Brainstem and Spinal Cord of Fibromyalgia Patients During the Anticipation and Experience of Experimental Pain

Abstract:

Chronic pain associated with fibromyalgia (FM) affects a large portion of the population but the underlying mechanisms leading to this altered pain are still poorly understood. Evidence suggests that FM involves altered neural processes in the central nervous system and neuroimaging methods such as functional magnetic resonance imaging (fMRI) are used to reveal these underlying alterations. While many fMRI studies of FM have been conducted in the brain, recent evidence shows that the changes in pain processing in FM may be linked to autonomic and homeostatic dysregulation, thus requiring further investigation in the brainstem and spinal cord.

Functional magnetic resonance imaging data from 15 women with FM and 15 healthy controls were obtained in the cervical spinal cord and brainstem at 3 tesla using previously established methods. In order to investigate differences in pain processing in these groups, participants underwent trials in which they anticipated and received a predictable painful stimulus, randomly interleaved with trials with no stimulus. Differences in functional connectivity between the groups were investigated by means of structural equation modeling.

The results demonstrate significant differences in brainstem/spinal cord network connectivity between the FM and control groups which also correlated with individual differences in pain responses. The regions involved in these differences in connectivity included the LC, hypothalamus, PAG, and PBN, which are known to be associated with autonomic homeostatic regulation, including fight or flight responses. This study extends our understanding of altered neural processes associated with FM and the important link between sensory and autonomic regulation systems in this disorder.

Source: Ioachim G, Warren HJM, Powers JM, Staud R, Pukall CF, Stroman PW. Altered Pain in the Brainstem and Spinal Cord of Fibromyalgia Patients During the Anticipation and Experience of Experimental Pain. Front Neurol. 2022 May 6;13:862976. doi: 10.3389/fneur.2022.862976. PMID: 35599729; PMCID: PMC9120571. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9120571/ (Full text)

The incidence and characteristics of chronic pain and fatigue after 12 months later admitting with COVID-19; The Post- COVID 19 syndrome

Abstract:

Introduction: This study aimed to evaluate chronic pain and fatigue in patients 12 months after hospitalization for Covid-19.

Methods: We studied the COVID-19 patients discharged from Hospital, March 10 and April 20, 2020.

Results: A total of 157 patients were included in this study. Forty-three patients (27.4%) complained of chronic fatigue and muscle weakness in the last six months. The visual analog fatigue scale (VAFS) score of 3.84 ± 1.48 was obtained. Forty patients (25.5%) were suspected of Chronic Fatigue Syndrome (CFS).Twenty-four patients (15.3%) had severe chronic pain or exacerbation of previous chronic pain, most of which were reported in the lower back (70.8%) and lower extremities (66.7%). Pain intensity had a mean score of 2.33 ± 0.87 and was mainly described as “muscle cramps,” “persistent dull pain,” and “boring and numbing.” In women, chronic pain and fatigue, extended hospital stays, ICU admission, and depressed mood were common than in men.For these pain and fatigue, 37% used nonsteroidal anti-inflammatory drugs, and 16.3% used antidepressants. Only one person had applied for physiotherapy, and none of the patients had received psychotherapy.

Conclusion: Fatigue and chronic pain in patients recovering from COVID-19 are common complications, even after 12 months of illness.

Source: Janbazi L, Kazemian A, Mansouri K, Madani SP, Yousefi N, Vahedifard F, Raissi G. The incidence and characteristics of chronic pain and fatigue after 12 months later admitting with COVID-19; The Post- COVID 19 syndrome. Am J Phys Med Rehabil. 2022 Apr 13. doi: 10.1097/PHM.0000000000002030. Epub ahead of print. PMID: 35473921. https://pubmed.ncbi.nlm.nih.gov/35473921/

Chronic Fatigue Syndrome and chronic pain conditions – vitally protective systems gone wrong

Abstract:

Chronic Fatigue Syndrome (CFS) and chronic pain syndromes represent major health problems in society. These conditions are disabling and strongly associated with low quality of life. Even though CFS and chronic pain are separate conditions, they have strikingly much in common. Both pain and fatigue are important sensations with protective value in an acute situation. It can be life-threatening not to be aware of them.

However, as these symptoms become chronic, their protective roles decrease and instead they become health problems. Our understanding of the perception of pain and fatigue has shifted through the years, from a dualistic biomedical point of view to a holistic biopsychosocial understanding. This combined with the increasing evidence of how our brain works in a predictive/anticipatory manner, gives a deeper understanding of why treatments like cognitive behavior therapies and stress relief therapies can help these patients recover to better health.

Source: Pedersen M. Chronic Fatigue Syndrome and chronic pain conditions – vitally protective systems gone wrong. Scand J Pain. 2019 Jun 29. pii: /j/sjpain.ahead-of-print/sjpain-2019-0072/sjpain-2019-0072.xml. doi: 10.1515/sjpain-2019-0072. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/31256069

Chronic Fatigue Syndrome: From Chronic Fatigue to More Specific Syndromes

Abstract:

In the last decade, a group of chronic disorders associated with fatigue (CDAF) emerged as the leading cause of chronic fatigue, chronic pain, and functional impairment, all of which have been often labeled in clinical practice as chronic fatigue syndrome (CFS) or fibromyalgia. While these chronic disorders arise from various pathophysiologic mechanisms, a shared autoimmune or immune-mediated etiology could shift the focus from symptomatic treatment of fatigue and pain to targeted immunomodulatory and biological therapy.

A clinical paradigm shift is necessary to reevaluate CFS and fibromyalgia diagnoses and its relationship to the CDAF entities, which would ultimately lead to a change in diagnostic and therapeutic algorithm for patients with chronic fatigue and chronic pain. Rather than uniformly apply the diagnoses of CFS or fibromyalgia to any patient presenting with unexplained chronic fatigue or chronic pain, it may be more beneficial and therapeutically effective to stratify these patients into more specific diagnoses in the CDAF group.

Source: Blitshteyn S, Chopra P. Chronic Fatigue Syndrome: From Chronic Fatigue to More Specific Syndromes. Eur Neurol. 2018 Oct 4;80(1-2):73-77. doi: 10.1159/000493531. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/30286454

Chronic Fatigue Syndrome and Chronic Widespread Pain in Adolescence: Population Birth Cohort Study

Abstract:

Although many studies have investigated the overlap between pain phenotypes and chronic fatigue syndrome (CFS) in adults, little is known about the relationship between these conditions in adolescents. The study’s aim was therefore to identify whether a relationship exists between chronic widespread pain (CWP) and CFS in adolescents and investigate whether the two share common associations with a set of covariates.

A questionnaire was administered to offspring of the Avon Longitudinal Study of Parents and Children (ALSPAC) at age 17, asking about site, duration, and pain intensity, from which participants with CWP were identified. At the same research clinic, a computer-based Revised Clinical Interview Schedule was filled out, from which a classification of CFS was obtained. The relationship between selected covariates and CFS and CWP was investigated using a variety of logistic, ordinal logistic, and multinomial regressions.

We identified 3,214 adolescents with complete data for all outcomes and covariates. There were 82 (2.6%) individuals classified as CFS and 145 (4.5%) as CWP. A classification of CFS resulted in an increased likelihood of having CWP (odds ratio = 3.87; 95% confidence interval, 2.05-7.31). Female adolescents were approximately twice as likely to have CFS or CWP, with multinomial regression revealing a greater sex effect for CWP compared with CFS.

Those with exclusive CFS were more likely to report higher levels of pain and greater effect of pain compared with those without CFS, although associations attenuated to the null after adjustment for covariates, which did not occur in those with exclusive CWP. Multinomial regression revealed that relative to having neither CFS nor CWP, a 1-unit increase in the depression and anxiety scales increased the risk of having exclusive CFS and, to a greater extent, the risk of having comorbid CFS and CWP, but not exclusive CWP, which was only related to anxiety.

PERSPECTIVE: In this cohort, 14.6% of adolescents with CFS have comorbid CWP. The likely greater proportion of more mild cases observed in this epidemiological study means that prevalence of overlap may be underestimated compared with those attending specialist services. Clinicians should be aware of the overlap between the 2 conditions and carefully consider treatment options offered.

Source: Norris T, Deere K, Tobias JH, Crawley E. Chronic Fatigue Syndrome and Chronic Widespread Pain in Adolescence: Population Birth Cohort Study. J Pain. 2016 Nov 12. pii: S1526-5900(16)30308-X. doi: 10.1016/j.jpain.2016.10.016. [Epub ahead of print] http://www.jpain.org/article/S1526-5900(16)30308-X/fulltext (Full article)

Role of psychological aspects in both chronic pain and in daily functioning in chronic fatigue syndrome: a prospective longitudinal study

Abstract:

In addition to fatigue, many patients with chronic fatigue syndrome (CFS) experience chronic musculoskeletal pain. We aimed at examining the role of catastrophizing, coping, kinesiophobia, and depression in the chronic pain complaints and in the daily functioning of CFS patients.

A consecutive sample of 103 CFS patients experiencing chronic widespread musculoskeletal pain completed a battery of questionnaires evaluating pain, daily functioning, and psychological characteristics (depression, kinesiophobia, pain coping, and catastrophizing).

Thirty-nine patients participated in the 6-12-month follow-up, consisting of questionnaires evaluating pain and pressure pain algometry. Correlation and linear regression analyses were performed to identify predictors. The strongest correlations with pain intensity were found for catastrophizing (r = -.462, p < .001) and depression (r = -.439, p < .001). The stepwise multiple regression analysis revealed that catastrophizing was both the immediate main predictor for pain (20.2%) and the main predictor on the longer term (20.1%). The degree of depression was responsible for 10% in the observed variance of the VAS pain after 6-12 months.

No significant correlation with pain thresholds could be revealed. The strongest correlations with daily functioning at baseline were found for catastrophizing (r = .435, p < .001) and depression (r = .481, p < .001). Depression was the main predictor for restrictions in daily functioning (23.1%) at baseline. Pain catastrophizing and depression were immediate and long-term main predictors for pain in patients with CFS having chronic widespread musculoskeletal pain. They were also correlated to daily functioning, with depression as the main predictor for restrictions in daily functioning at baseline.

Source: Meeus M, Nijs J, Van Mol E, Truijen S, De Meirleir K. Role of psychological aspects in both chronic pain and in daily functioning in chronic fatigue syndrome: a prospective longitudinal study. Clin Rheumatol. 2012 Jun;31(6):921-9. doi: 10.1007/s10067-012-1946-z. Epub 2012 Feb 16. https://www.ncbi.nlm.nih.gov/pubmed/22349876

Assessment of fibromyalgia & chronic fatigue syndrome: a new protocol designed to determine work capability–chronic pain abilities determination (CPAD)

Abstract:

The objective was to design a protocol to assess work ability in people suffering ill-defined painful and disabling disorders, the outstanding prototype of which is fibromyalgia/chronic fatigue syndrome (FM/CSF).Following an extensive literature search, the mos appropriate components of current methods of assessment of physical and cognitive abilities were incorporated into the protocol, occasionally with appropriate modification to suit the specific requirements of the individual.

The initial part of the assessment consists of a standard history taking, principally focusing on the patient’s self-reported physical and cognitive abilities and disabilities, as well as the completion of established pain and fatigue scales, and relevant disability questionnaires.

Following this, physical and cognitive abilities are objectively assessed on two separate occasions, utilizing computerized hand-held dynamometers, inclinometers, algometers, and force dynamometers. Specific work simulation tests using the industrial standards Methods-Time-Measurement testing are availed of, as is aerobic testing using the Canadian Aerobic Fitness Test (CAFT). Objective computerised neuro-cognitive testing are also utilised as an integral component of the assessment. All results are then subject to specific computerized analysis and compared to normative and standardised work-based databases.

The designed system produces reliable, consistent and reproducible results. It also proves capable of detecting any inconsistencies in patient input and results, in addition to being independent of any possible assessor bias. A new protocol has been designed to determine the working capability of individuals who suffer from various chronic disabling conditions, and represents a significant step forward in a difficult but rapidly expanding area of medical practice.

Source: Kelly M, Gagne R, Newman JD, Olney C, Gualtieri C, Trail D. Assessment of fibromyalgia & chronic fatigue syndrome: a new protocol designed to determine work capability–chronic pain abilities determination (CPAD). Ir Med J. 2008 Oct;101(9):277-8. https://www.ncbi.nlm.nih.gov/pubmed/19051616

Chronic pain and fatigue syndromes: overlapping clinical and neuroendocrine features and potential pathogenic mechanisms

Abstract:

Patients with unexplained chronic pain and/or fatigue have been described for centuries in the medical literature, although the terms used to describe these symptom complexes have changed frequently. The currently preferred terms for these syndromes are fibromyalgia and chronic fatigue syndrome, names which describe the prominent clinical features of the illness without any attempt to identify the cause.

This review delineates the definitions of these syndromes, and the overlapping clinical features. A hypothesis is presented to demonstrate how genetic and environmental factors may interact to cause the development of these syndromes, which we postulate are caused by central nervous system dysfunction. Various components of the central nervous system appear to be involved, including the hypothalamic pituitary axes, pain-processing pathways, and autonomic nervous system. These central nervous system changes lead to corresponding changes in immune function, which we postulate are epiphenomena rather than the cause of the illnesses.

Source: Clauw DJ, Chrousos GP. Chronic pain and fatigue syndromes: overlapping clinical and neuroendocrine features and potential pathogenic mechanisms. Neuroimmunomodulation. 1997 May-Jun;4(3):134-53. http://www.ncbi.nlm.nih.gov/pubmed/9500148