Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0016053 (fibromyalgia)
 4,687 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Drug addiction and multiple chemical intolerance (abdiction) appear to be polar opposites--the former characterized by craving and dependency, the latter by aversion. However, when the two are viewed in juxtaposition similarities emerge, revealing a common underlying dynamic, one which appears to be a new paradigm of disease. TILT, or toxicant-induced loss of tolerance, bridges the gap between addiction and abduction and has the potential to explain a variety of illnesses, including certain cases of asthma, migraine headaches and depression, as well as chronic fatigue syndrome, fibromyalgia and "Gulf War syndrome". This paper argues that both addiction and chemical intolerance involve a fundamental breakdown in innate tolerance, resulting in an amplification of various biological effects, particularly withdrawal symptoms. While addicts seek further exposures so as to avoid unpleasant withdrawal symptoms, chemically intolerant individuals shun their problem exposures, but for the same reason--to avoid unpleasant withdrawal symptoms. These observations raise critical questions: do addictive drugs and environmental pollutants initiate an identical disease process? Once this process begins, can both addictants and pollutants trigger symptoms and cravings? TILT opens a new window between the fields of addiction and environmental medicine, one that has the potential to transform neighboring realms of medicine, psychology, psychiatry and toxicology.
 ...
PMID:Toxicant-induced loss of tolerance. 1117 24

In science, anomalies expose the limitations of existing paradigms and drive the search for new ones. In the late 1800s, physicians observed that certain illnesses spread from sick, feverish individuals to those contacting them, paving the way for the germ theory of disease. The germ theory served as a crude, but elegant formulation that explained dozens of seemingly unrelated illnesses affecting literally every organ system. Today, we are witnessing another medical anomaly-a unique pattern of illness involving chemically exposed groups in more than a dozen countries, who subsequently report multisystem symptoms and new-onset chemical, food, and drug intolerances. These intolerances may be the hallmark for a new disease process or paradigm, just as fever is a hallmark for infection. The fact that diverse demographic groups, sharing little in common except some initial chemical exposure event, develop these intolerances is a compelling anomaly pointing to a possible new theory of disease, one that has been referred to as "Toxicant-Induced Loss of Tolerance" ("TILT"). TILT has the potential to explain certain cases of asthma, migraine headaches, and depression, as well as chronic fatigue, fibromyalgia, and "Gulf War syndrome". It appears to evolve in two stages: (1) initiation, characterized by a profound breakdown in prior, natural tolerance resulting from either acute or chronic exposure to chemicals (pesticides, solvents, indoor air contaminants, etc.), followed by (2) triggering of symptoms by small quantities of previously tolerated chemicals (traffic exhaust, fragrances, gasoline), foods, drugs, and food/drug combinations (alcohol, caffeine). While the underlying dynamic remains an enigma, observations indicating that affected individuals respond to structurally unrelated drugs and experience cravings and withdrawal-like symptoms, paralleling drug addiction, suggest that multiple neurotransmitter pathways may be involved.
 ...
PMID:The compelling anomaly of chemical intolerance. 1200 12

Inadequately treated acute and chronic pain remains a major cause of suffering and dissatisfaction in pain therapy. A cause for the variable success of pharmacologic pain therapy is the different genetic disposition of patients to develop pain or to respond to analgesics. The patient's phenotype may be regarded as the result of synergistic or antagonistic effects of several genetic variants concomitantly present in an individual. Variants modulate the risk of developing painful disease or its clinical course (e.g., migraine, fibromyalgia, low back pain). Other variants modulate the perception of pain (e.g., OPRM1 or GCH1 variants conferring modest pain protection by increasing the tone of the endogenous opioid system or decreasing nitric oxide formation). Other polymorphisms alter pharmacokinetic mechanisms controlling the local availability of active analgesic molecules at their effector sites (e.g., decreased CYP2D6 related prodrug activation of codeine to morphine). In addition, genetic variants may alter pharmacodynamic mechanisms controlling the interaction of the analgesic molecules with their target structures (e.g., opioid receptor mutations). Finally, opioid dosage requirements may be increased depending on the risk of drug addiction (e.g., DRD2 polymorphisms decreasing the functioning of the dopaminergic reward system). With the complex nature of pain involving various mechanisms of nociception, drug action, drug pharmacology, pain disease and possibly substance addiction, a multigenic or even genome wide approach to genetics could be required to base individualized pain therapy on the patient's genotype.
 ...
PMID:Genetic modulation of the pharmacological treatment of pain. 1961 6

Fibromyalgia (FM), a poorly understood rheumatic condition, is characterized by chronic pain and psychiatric comorbidities, most notably depression and anxiety. Additional symptoms include sleep difficulties, fatigue, and various cognitive impairments. Furthermore, FM is surrounded by social stigma, due to the unclear nature and etiology of this condition. While there is widespread evidence for the emotional and psychological suffering of those with FM, the scope of suicidality, as well as the underlying factors that are associated with suicidal ideation and behavior among this population, are not well understood. The present review, which is the first of its kind, aims to summarize existing data on the prevalence of suicide-related outcomes among FM patients, highlight factors associated with suicidal ideation and behavior in FM, and identify gaps in the literature to better inform research and clinical care. Studies were extracted from the literature that measured suicidal ideation, attempted suicide, and/or completed suicide among FM patients. Results indicated that both suicidal ideation and suicidal behavior were prevalent among individuals suffering from FM. Psychiatric comorbidity, sleep difficulties, and inpatient hospitalization were associated with both suicidal ideation and suicidal behavior. Functional impairment was associated with suicidal ideation in FM. Factors associated with higher levels of suicidal behavior in FM included female gender, unemployment and lower income, medical comorbidity, and drug dependence. While an understanding of currently recognized risk factors is important for improving FM research and clinical care, some clear methodological and conceptual limitations of the reviewed studies were identified. Future work should focus on longitudinal studies, as well as on gaining a better biological and psychological understanding of the underpinnings of FM and suicidality.
 ...
PMID:Suicidality in Fibromyalgia: A Systematic Review of the Literature. 3317 5