The T102C Polymorphism of the 5-HT2A-Receptor Gene in Fibromyalgia

doi:10.1006/nbdi.1999.0262

Neurobiology of Disease

Volume 6, Issue 5, October 1999, Pages 433-439

https://doi.org/10.1006/nbdi.1999.0262 Get rights and content

Abstract

Based on a possible involvement of serotonergic dysfunction in the pathophysiology of fibromyalgia (FM) and on preliminary reports of a possible genetically driven vulnerability for this disorder we investigated the silent T102C polymorphism of the 5-HT2A-receptor gene in 168 FM patients and 115 healthy controls. Our results showed a significantly different genotype distribution in FM patients with a decrease in T/T and an increase in both T/C and C/C genotypes as compared to the control population (Fisher's Exact test, two-sided, P = 0.008). However, the increase in allele-C102 frequency felt short of significance (P = 0.07). Correlation of genotypes to clinical parameters revealed no influences on age of onset, duration of disease or psychopathological symptoms, measured with the Beck Depression Inventory and the symptom checklist SCL-90-R. In contrast to that the pain score, being a self reported information on pain severity, was significantly higher in patients of the T/T genotype (Mann–Whitney U test, P = 0.028). This suggests that the T102-allele might be involved in the complex circuits of nociception. However, the T102C polymorphism is not directly involved in the aetiology of FM but might be in linkage dysequilibrium with the true functional variant, which has to be unravelled.

References (37)

B.G. Almay et al.
5-HIAA and HVA in CSF in patients with idiopathic pain disorders
Biol. Psychiatry
(1987)
B.G. Almay et al.
Substance P in CSF of patients with chronic pain syndromes
Pain
(1988)
M. Arranz et al.
Association between clozapine response and allelic variation in 5-HT2A receptor gene
Lancet
(1995)
M.J. Arranz et al.
5-HT2A receptor and bipolar affective disorder: Association studies in affected patients
Neurosci. Lett.
(1997)
D. Buskila et al.
Familial aggregation in the fibromyalgia syndrome
Semin. Arthritis Rheum.
(1996)
L.J. Crofford et al.
Neurohormonal perturbations in fibromyalgia
Baillieres. Clin. Rheumatol
(1996)
M.A. Demitrack
Neuroendocrine correlates of chronic fatigue syndrome: A brief review
J. Psychiatr. Res.
(1997)
M.A. Demitrack
Chronic fatigue syndrome and fibromyalgia. Dilemmas in diagnosis and clinical management
Psychiatr. Clin. North Am.
(1998)
J.I. Hudson et al.
The concept of affective spectrum disorder: relationship to fibromyalgia and other syndromes of chronic fatigue and chronic muscle pain
Baillieres. Clin. Rheumatol.
(1994)
M.J. Schwarz et al.
Relationship of substance P, 5-hydroxyindolic acetic acid and tryptophan in serum of fibromyalgia patients
Neuroscience Letters
(1999)

A. Tokunaga et al.

5-HT2A receptor subtype is involved in the thermal hyperalgesic mechanism of serotonin in the periphery

Pain

(1998)

J.N. Butcher et al.

Minnesota Multiphasic Personality Inventory (MMPI-2) Manual for Administering and Scoring

(1989)

C.R. Cloninger

A systematic method for clinical description and classification of personality variants. A proposal

Arch. Gen. Psychiatry

(1987)

Costa, P. T, &, McCrae, R. R. 1992, Revised NEO Personality Inventory (NEO PI-R) and NEO Five Factor Inventory....

J. Erdmann et al.

Systematic screening for mutations in the human serotonin-2A (5-HT2A) receptor gene: Identification of two naturally occurring receptor variants and association analysis in schizophrenia

Hum. Genet.

(1996)

A. Farmer et al.

Is disabling fatigue in childhood influenced by genes

Psychol. Med.

(1999)

K. Fassbender et al.

Tender points, depressive and functional symptoms: Comparison between fibromyalgia and major depression

Clin. Rheumatol.

(1997)

D.L. Goldenberg et al.

High frequency of fibromyalgia in patients with chronic fatigue seen in a primary care practice

Arthritis Rheum.

(1990)

Cited by (175)

Are psychedelic medicines the reset for chronic pain? Preliminary findings and research needs
2023, Neuropharmacology
Chronic pain is a leading cause of disability, reduced productivity, healthcare seeking behavior, and a contributor to opioid overdose in the United States. For many people, pain can be satisfactorily managed by existing medicines and comprehensive psychosocial treatments. For others, available treatments are either ineffective or not acceptable, due to side effects and concerns about risks. Preliminary evidence suggests that some psychedelics may be effective for certain types of pain and/or improved quality of life with increased functionality and reduced disability and distress in people whose pain may never be completely relieved. Efficacy in these quality-of-life related outcomes would be consistent with the 'reset in thinking' about chronic pain management being increasingly called for as a more realistic goal for some people as compared to complete elimination of pain. This commentary summarizes the rationale for conducting more basic research and clinical trials to further explore the potential for psychedelics in chronic pain management. Additionally, if shown to be effective, to then determine whether the effects of psychedelics are primarily due to direct antinociceptive or anti-inflammatory mechanisms, or via increased tolerability, acceptance, and sense of spirituality, that appear to at least partially mediate the therapeutic effects of psychedelics observed in psychiatric disorders such as major depression. This commentary represents a collaboration of clinical and more basic scientists examining these issues and developing recommendations for research ranging from neuropharmacology to the biopsychosocial treatment factors that appear to be as important in pain management as in depression and other disorders in which psychedelic medicines are under development.
This article is part of the Special Issue on "National Institutes of Health Psilocybin Research Speaker Series".
Republication of: “Therapeutic Patient Education for Fibromyalgia during Spa Therapy: The FiETT Randomized Controlled Trial”
2022, Douleurs
La cure thermale est connue pour améliorer la qualité de vie et diminuer la douleur. Nous avons évalué l’efficacité (Fibromyalgia Impact Questionnaire-FIQ) et l’innocuité à 6 mois d’un programme d’éducation thérapeutique du patient (ETP) spécifique à la fibromyalgie, ajouté à la cure thermale standardisée (SST) adaptée à la fibromyalgie, comparée à la SST seule, dans un essai contrôlé randomisé. Nous avons recruté 157 patients, majoritairement des femmes, fréquentant des centres thermaux du Sud-Ouest de la France, en 2015–2016, et les avons randomisés en SST + TPE (79) ou SST (78). L’analyse en intention de traiter avec « manque comme échec » a montré une tendance vers un bénéfice plus élevé, quoique non significatif, avec l’ETP sur le FIQ (−9 vs −3 ; p = 0,053) ou l’intensité de la douleur (−0,9 contre −1,1 ; p = 0,58). Nous expliquons le défaut de bénéfice significatif de l’ETP, évalué à partir du FIQ, par le fait que nos participants, appartenant à des associations de patients fibromyalgiques, étaient déjà bien informés et bien encadrés. À noter, la bonne tolérance des cures thermales avec peu d’effets indésirables et surtout que 87 % des patients du bras SST + TPE pratiquaient encore régulièrement, à 6 mois, les exercices physiques qui leur avaient été enseignés. En outre, le soulagement de la douleur (+3,2 vs. +4,3 ; p = 0,03) et la fatigue (−1,6 vs. −3,7 ; p = 0,02) étaient significativement améliorées, la prise médicamenteuse diminuée de façon nette.
Spa therapy is known to improve quality of life and diminish pain. We assessed the efficacy (Fibromyalgia Impact Questionnaire-FIQ) and safety at 6 months of a fibromyalgia-specific therapeutic patient education (TPE) program added to fibromyalgia-specific standardized spa therapy (SST), compared to SST alone, in a controlled randomized trial. We enrolled 157 patients, mostly women, attending spa centers in Southwest France in 2015–2016, and randomized them to SST + TPE (79) or SST (78). The intention-to-treat with “missing as failure” analysis showed a tendency toward a higher, though non-significant, benefit with TPE than without for FIQ (−9 vs. −3; P = 0.053) or pain intensity (−0.9 vs. −1.1; P = 0.58). In addition, pain relief (+3.2 vs. +4.3; P = 0.03) and fatigue (−1.6 vs. −3.7; P = 0.02) were significantly improved, and 87% patients in the SST + TPE arm still regularly practiced the physical exercises taught to them at 6 months. We suspect significant and lasting improvement from spa therapy, as well as our already well-informed and well-managed participants, to have prevented the demonstration of a significant benefit of TPE on FIQ.
Modality selective roles of pro-nociceptive spinal 5-HT<inf>2A</inf> and 5-HT<inf>3</inf> receptors in normal and neuropathic states
2018, Neuropharmacology
Citation Excerpt :
However, intrathecal ondansetron produces conditioned place preference selectively in neuropathic rats demonstrating that enhanced serotonergic activity via spinal 5-HT3Rs can lead to an ongoing aversive state, and supports a partial separation of sensory and affective processing (Wang et al., 2013). Polymorphisms of the 5-HT2AR are associated with fibromyalgia, a condition considered to be dependent on altered central modulation (Bondy et al., 1999), and 5-HT3Rs are highly expressed in human dorsal root ganglion neurones (Ray et al., 2018) supporting involvement of these receptors in pain modulation in humans. Few clinical reports exist examining the effect of 5-HT2A antagonists in chronic pain patients.
Descending brainstem control of spinal nociceptive processing permits a dynamic and adaptive modulation of ascending sensory information. Chronic pain states are frequently associated with enhanced descending excitatory drive mediated predominantly through serotonergic neurones in the rostral ventromedial medulla. In this study, we examine the roles of spinal 5-HT_2A and 5-HT₃ receptors in modulating ascending sensory output in normal and neuropathic states. In vivo electrophysiology was performed in anaesthetised spinal nerve ligated (SNL) and sham-operated rats to record from wide dynamic range neurones in the ventral posterolateral thalamus. In sham rats, block of spinal 5-HT₃Rs with ondansetron revealed tonic facilitation of noxious punctate mechanical stimulation, whereas blocking 5-HT_2ARs with ketanserin had minimal effect on neuronal responses to evoked stimuli. The inhibitory profiles of both drugs were altered in SNL rats; ondansetron additionally inhibited neuronal responses to lower intensity punctate mechanical stimuli and noxious heat evoked responses, whereas ketanserin inhibited innocuous and noxious evaporative cooling evoked responses. Neither drug had any effect on dynamic brush evoked responses nor on spontaneous firing rates in both sham and SNL rats. These data identify novel modality and intensity selective facilitatory roles of spinal 5-HT_2A and 5-HT₃ receptors on sensory neuronal processing within the spinothalamic-somatosensory cortical pathway.
Depressive Disorder, Anxiety Disorder and Chronic Pain: Multiple Manifestations of a Common Clinical and Pathophysiological Core
2018, Revista Colombiana de Psiquiatria
Una alta proporción de los trastornos depresivos se acompañan de manifestaciones ansiosas, así como la depresión y la ansiedad cursan frecuentemente con dolor. En otro sentido, las manifestaciones dolorosas causan o empeoran los síntomas depresivos y ansiosos. Cada vez hay más evidencia sobre la similitud fisiopatológica, imagenológica y neurofisiológica del dolor y la depresión.
Revisión narrativa de los aspectos fisiopatológicos y clínicos de la comorbilidad depresión y dolor crónico. Se incluyen los artículos de investigación que enfatizan los elementos relevantes relacionados con la comprensión de la fisiopatología de ambas manifestaciones.
Con los más recientes avances en técnicas bioquímicas y celulares y el advenimiento de tecnologías imagenológicas de avanzada, se ha podido considerar cada vez más claramente la aproximación etiopatogénica, fisiopatológica y clínica de estos trastornos. Se sistematiza esta información en imágenes y cuadros comprensivos.
El reconocimiento de que el polimorfismo de los genes relacionados con la inflamación genera susceptibilidad a las manifestaciones depresivas y puede modificar la respuesta a los tratamientos antidepresivos establece que la respuesta inflamatoria no solo es un componente etiopatogénico del dolor, sino del estrés y la depresión. De igual manera, la similitud en la aproximación con imágenes corrobora la analogía no solo estructural, sino también funcional y fisiopatológica, entre la depresión y el dolor crónico. El conocimiento de la comorbilidad depresión-ansiedad-dolor crónico es importante en la búsqueda de intervenciones terapéuticas eficaces.
A high proportion of depressive disorders are accompanied by anxious manifestations, just as depression and anxiety often present with many painful manifestations, or conversely, painful manifestations cause or worsen depressive and anxious expressions. There is increasingly more evidence of the pathophysiological, and neurophysiological and technical imaging similarity of pain and depression.
Narrative review of the pathophysiological and clinical aspects of depression and chronic pain comorbidity. Research articles are included that emphasise the most relevant elements related to understanding the pathophysiology of both manifestations.
The pathological origin, physiology and clinical approach to these disorders have been more clearly established with the latest advances in biochemical and cellular techniques, as well as the advent of imaging technologies. This information is systematised with comprehensive images and clinical pictures.
The recognition that the polymorphism of inflammation-related genes generates susceptibility to depressive manifestations and may modify the response to antidepressant treatments establishes that the inflammatory response is not only an aetiopathogenic component of pain, but also of stress and depression. Likewise, the similarity in approach with images corroborates not only the structural, but the functional and pathophysiological analogy between depression and chronic pain. Knowledge of depression-anxiety-chronic pain comorbidity is essential in the search for effective therapeutic interventions.
Genetic predictors of human chronic pain conditions
2016, Neuroscience
Chronic pain conditions are multifactorial disorders with a high frequency in the population. Their pathophysiology is often unclear, and treatment is inefficient. During the last 20 years, genetic linkage analysis and association studies have made considerable strides toward identifying key molecular contributors to the onset and maintenance of chronic pain. Here, we review the genetic variants that have been implicated in chronic pain conditions, divided into the following etiologically-grouped categories: migraine, musculoskeletal pain disorders, neuropathic pain disorders, and visceral pain disorders. In rare familial monogenic pain conditions several strong-effect mutations have been identified. In contrast, the genetic landscape of common chronic pain conditions suggests minor contributions from a large number of single nucleotide polymorphisms representing different functional pathways. A comprehensive survey of up-to-date genetic association results reveals migraine and musculoskeletal pain to be the most investigated chronic pain disorders, in which nearly half of identified genetic variability alters neurotransmission pathways.
Pharmacogenetics and Personalized Medicine in Pain Management
2016, Clinics in Laboratory Medicine

View all citing articles on Scopus

View full text

Regular ArticleThe T102C Polymorphism of the 5-HT2A-Receptor Gene in Fibromyalgia

Abstract

Biol. Psychiatry

Pain

Lancet

Neurosci. Lett.

Semin. Arthritis Rheum.

Baillieres. Clin. Rheumatol

J. Psychiatr. Res.

Psychiatr. Clin. North Am.

Baillieres. Clin. Rheumatol.

Neuroscience Letters

Pain

Minnesota Multiphasic Personality Inventory (MMPI-2) Manual for Administering and Scoring

A systematic method for clinical description and classification of personality variants. A proposal

Arch. Gen. Psychiatry

Systematic screening for mutations in the human serotonin-2A (5-HT2A) receptor gene: Identification of two naturally occurring receptor variants and association analysis in schizophrenia

Hum. Genet.

Is disabling fatigue in childhood influenced by genes

Psychol. Med.

Tender points, depressive and functional symptoms: Comparison between fibromyalgia and major depression

Clin. Rheumatol.

High frequency of fibromyalgia in patients with chronic fatigue seen in a primary care practice

Arthritis Rheum.

Regular Article
The T102C Polymorphism of the 5-HT2A-Receptor Gene in Fibromyalgia