NEUROBIOLOGY OF CHRONIC MUSCLE PAIN

Grant Number: 5R01NS039734-03
PI Name: SLUKA, KATHLEEN A.
PI Title:
Project Title: NEUROBIOLOGY OF CHRONIC MUSCLE PAIN

Abstract: DESCRIPTION (taken from the application): Although 14% of the United States population suffers from chronic musculoskeletal pain, most of our knowledge about pain has been obtained from studies on cutaneous pain. The current models of musculoskeletal pain typically produce short term hyperalgesia (resolved in 24 h or less). However, clinically, chronic muscle pain, as experienced by people with fibromyalgia, is long lasting (months to years). In preliminary studies, I determined that a long lasting bilateral hyperalgesia can be induced by two injections of low pH saline, five days apart, into one gastrocnemius muscle. In the work proposed I hypothesize that the development of the long lasting bilateral hyperalgesia is dependent initially on input from the site of injection following both the first and second injection. I further propose that once the long lasting hyperalgesia develops plastic changes in the central nervous system occur that maintain the hyperalgesia through increased activity in spinal neurons. The specific aims will establish and characterize a new model of muscle pain that is chronic and widespread. The proposed studies will establish if the neural mechanisms involved in the development and maintenance of chronic pain, induced by stimulation of muscle nociceptors, involve peripheral or central nervous system processes. These proposed studies will help in the understanding and thus potential treatment of chronic muscle pain, including such conditions as fibromyalgia, myofascial pain and low back pain.

Thesaurus Terms: chronic disease /disorder, disease /disorder model, fibromyalgia, model design /development, neurobiology acidity /alkalinity, dorsal horn, glutamate receptor, heat injury, hyperalgesia, neuron injection /infusion, laboratory rat

Institution:
Fiscal Year: 2001
Department:
Project Start:
Project End:
ICD: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
IRG:

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EMPLOYMENT AND HEALTH STATUS IN WOMEN WITH FIBROMYALGIA

Grant Number: 5R01AR046041-03
PI Name: REISINE, SUSAN T.
PI Title: PROFESSOR AND HEAD
Project Title: EMPLOYMENT AND HEALTH STATUS IN WOMEN WITH FIBROMYALGIA

Abstract: Preliminary data on women with rheumatoid arthritis (RA) indicate that those who are able to enter and leave the work force experience the best health outcomes; homemakers report the worst health. These findings raise several new questions about the dynamic relationship among paid work, unpaid family work and health status among women with rheumatic diseases and whether these results hold for other musculoskeletal conditions. We propose to study women with primary fibromyalgia syndrome (FMS) and to describe prospectively the simultaneous evolution of health status, paid work status, unpaid family work, and daily stressors. Women with MS will be compared to a control group similar in age, race, and employment status. Finding from the study will shed light on the relationships among paid and unpaid family work and physical and psychological health status. We will recruit a sample of 245 women diagnosed with FMS and 250 healthy women from the community similar in age, race, and employment status. The total sample will consist of equal groups of those who are employed outside the home and those who are not currently employed. Patients will be recruited from a national sample of rheumatologists who are fellows in the ACR. Annual interviews will be conducted with participants from a national sample of rheumatologists who are fellows in the ACR. Annual interviews will be conducted with participants to collect detailed data on family and employment structure and functional status. Participants to collect detailed data on family and employment structure and functional status. Participants also will complete a daily diary for one week at the time of the baseline and annual interviews each year to collect detailed data on daily stressors as possible mediator of work and family structure on functional status. The proposed study will provide data describing the natural course of paid and unpaid family work and health status among FMS patients and control subjects and will address questions about the relationship between paid work, unpaid family work structure and the physical and psychological health status of women with FMS and controls. The data will be analyzed first, using descriptive statistics in order to describe the experiences of the patients and controls in the study; second, MANOVA and MANCOVA techniques will be used to assess differences in health status between groups at baseline and to assess changes over time in health status between groups adjusting for covariates.

Thesaurus Terms: employment of women, fibromyalgia, quality of life, women's health family, functional ability, health behavior, occupational psychology, personal log /diary, psychological stressor, rheumatoid arthritis behavioral /social science research tag, clinical research, female, human subject, interview

Institution: UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
Fiscal Year: 2001
Department: BEHAV SCIS & COMMUNITY HEALTH
Project Start: 01-JUL-1999
Project End: 30-JUN-2004
ICD: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES
IRG: ZAR1

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FIBROMYALGIA, DEPRESSION AND MYOFASCIAL TMD
Grant Number: 1R01DE13486-03
PI Name: RAPHAEL, KAREN G.
PI Title:
Project Title: FIBROMYALGIA, DEPRESSION AND MYOFASCIAL TMD

Abstract:
DESCRIPTION (taken from the application): The well-established comorbidity of fibromyalgia (FMS) and major depression (MDD) has motivated speculations about the direction of the relationship.

Three principal hypotheses to be tested here are:

(l)that FMS is a variant of depression;

(2) that MDD in FMS sufferers is a reaction to FMS; and

(3) that high rates of MDD in FMS patients are an artifact of studying treatment-seekers.

The proposed study's first aim is to support one and refute other hypotheses, by conducting a family study. Community women meeting criteria for FMS (n= 120) will be stratified so that half (n=60) have a lifetime history of MDD. Demographically-matched non-FMS controls (n= 120) from the same sampling frame will also be stratified on MDD status. Direct psychiatric interviews and physical examinations will be conducted with probands and all their available adult first degree relatives.

To support the first hypothesis, familial MDD rates should be elevated in FMS probands, even among probands with no personal depression histories; to support the second, probands with FMS and MDD should have low familial depression rates, as their depression should be more likely reactive to FMS; to support the last, familial MDD should be elevated in probands with MDD histories themselves, regardless of FMS status.

A second aim, prompted by the comorbidity of FMS and myofascial temporomandibular disorder (M/TMD), is test (1) whether M/TMD is a regional manifestation of FMS or (2) whether M/TMD comorbid with FMS is different from M/TMD expressed as a regional disorder.

To accomplish this aim, we will first reconfirm that FMS is familial, utilizing data gathered to satisfy the first aim. Second, we will reconstitute the groups from Aim 1, according to both FMS and M/TMD status. Rates of familial M/TMD in FMS and control probands, broken down by proband M/TMD status, will be examined. If M/TMD is found in the family of FMS probands, regardless of proband M/TMD status, this will support the first hypothesis. If only FMS probands have familial M/TMD but M/TMD probands do not, this will support the 2nd hypothesis and indicate that the two disorders are provoked through different pathogenic processes.

Thesaurus Terms: comorbidity, fibromyalgia, major depression, temporomandibular joint syndrome disease /disorder etiology, family genetics, mental health epidemiology clinical research, female, human subject, interview, statistics /biometry

Institution: UNIV OF MED/DENT NJ NEWARK
Fiscal Year: 2001
Department: PSYCHIATRY
Project Start: 01-JUL-1999
Project End: 30-JUN-2003
ICD: NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH
IRG: ZAR1

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FIBROMYALGIA AND TMD IN YOUNG WOMEN - A MULTIRACIAL STUDY

Grant Number: 5R01DE013487-02
PI Name: PLESH, OCTAVIA
PI Title: PROFESSOR
Project Title: FIBROMYALGIA AND TMD IN YOUNG WOMEN-A MULTIRACIAL STUDY

Abstract: This investigation will determine the relationship of temporomandibular disorders (TMDs) with fibromyalgia (FM) and factors associated with the two conditions in an established, populations-based cohort (51% black, 49% white) women; and assess racial differences regarding prevalence and the factors explaining this difference. This cohort has been participating for 10 years in the longitudinal National Heart Lung and Blood Institute Growth and Health Study (NGHS) conducted by the University of California, Berkeley and the University of Cincinnati The specific aims are: 1) to assess the prevalence of self-reported, common chronic pains (including TMD and FM) based on questionnaires and to identify potential TMD, FM, and regional chronic pain (RCP) cases and controls; 2) to clinically determine combined body pain and TMD status based on palpating tender points and the distribution of TMD diagnostic types; 3) to compare potential explanatory risk factors (predictors) for these groups and determine the temporal relationship between NGHS-collected factors and diagnostic group status; 4) to analyze factors responsible for racial differences. The cohort consists of 1573 women currently 18-19 years old, recruited from west Contra Costa County, CA and the greater Cincinnati area. Longitudinal data collected over 10 years in the NGHS study regarding physical development, (e.g. growth, sexual development, and reproductive health history) and psychosocial development (e.g. coping strategies inventory and family environmental scale) will be assessed as potential risk factors for combined body pain and TMD group status. These longitudinal data collected during the development of this cohort offer a unique opportunity to study multiple risk factors thought to be associated with different types of chronic pain such as FM and TMDs, as they enter the most vulnerable period of life for developing such conditions. Our proposed study will be able to examine the interconnectedness of the longitudinal psychosocial and physiological measures with cross-sectional FM and TMD status, enabling a case-control design to draw conclusions like a longitudinal study.

Thesaurus Terms: chronic pain, female, fibromyalgia, racial /ethnic difference, social psychology, temporomandibular joint syndrome comorbidity, epidemiology, hyperalgesia, longitudinal human study, psychometrics, socioeconomics behavioral /social science research tag, clinical research, human subject

Institution: UNIVERSITY OF CALIFORNIA SAN FRANCISCO
Fiscal Year: 2000
Department: RESTORATIVE DENTISTRY
Project Start: 25-SEP-1999
Project End: 31-AUG-2002
ICD: NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH
IRG: ZAR1

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INDOOR AIR ODORS EFFECT ON BRAIN AND BEHAVIOR
Grant Number: 1R15ES08838-01
PI Name: LORIG, TYLER S.
PI Title:
Project Title: INDOOR AIR ODORS EFFECT ON BRAIN AND BEHAVIOR

Abstract:
DESCRIPTION: (Adapted from the APPLICANT'S ABSTRACT) Indoor air quality continues to be an area of public concern even after the enactment of legislation restricting smoking and other potentially hazardous practices. Much of the current concern about indoor air is related to odors, and specifically to perfumes, perfumed hygiene products and room "de-odorizers." Legislation was recently introduced in Marin County, California to restrict the use of fragrance products in county buildings. Other public organizations have already restricted fragrance use in buildings (School of Social Work, University of Minnesota) and "artificial odors" are often cited as contributing to or triggering debilitating episodes for sufferers of multiple chemical sensitivity disorder. Despite the public concern for the effects of fragrances, little peer-reviewed scientific evidence exists about the effect of these odors on health, behavior, and self-reports of well-being, and the studies which do address this topic are mixed as to their findings. The proposed research project seeks to evaluate the effects of odorants such as perfumes, room de-odorizers, and food odors on cognitive performance and associated neurophysiological responses. Specifically, the effects of odors will be tested on subjects completing behavioral studies of linguistic processing and spatial processing. Preliminary data suggest that odors differentially affect these tasks. Electrophysiological recordings (event-related potentials) will be made during the linguistic, spatial, and odor stimuli to evaluate the potential neural and attentional mechanisms influenced by the odors. An important feature of this project is the use of auditory and visual stimuli as control conditions. Since any type of stimulus introduced during a cognitive task may impede performance, control stimuli will be introduced in a manner similar to the odor stimuli. This will allow any odor effects on performance and/or electrophysiology to be compared relative to effects in other modalities. The specific aims of this project are 1) to introduce a behavioral/electrophysiological paradigm for the evaluation of potentially distracting odors, 2) to use the paradigm to evaluate typical odors found in room air and quantify their effects on task performance and neurophysiology, and 3) to expand research opportunities for undergraduate students.

Thesaurus Terms:
air pollution odor, attention, behavior test, consumer product, food odor, neural information processing, neurophysiology, performance, space perception, cognition, environmental health, evoked potential, neurologic manifestation, psycholinguistics, quality of life, sensory mechanism, visual stimulus, behavioral /social science research tag, clinical research, electrophysiology, human subject, statistics /biometry

Institution: WASHINGTON AND LEE UNIVERSITY
LEXINGTON, VA 24450
Fiscal Year: 1997
Department: PSYCHOLOGY
Project Start: 01-APR-97
Project End: 31-MAR-99
ICD: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
IRG: ZRG4

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PERSIAN GULF WAR SYNDROME--STUDY OF NEUROENDOCRINE AXIS
Grant Number: 5M01RR00334-33S30488
PI Name: BENNETT, ROBERT M.
PI Title:
Project Title: PERSIAN GULF WAR SYNDROME--STUDY OF NEUROENDOCRINE AXIS

Abstract:
Persian Gulf War veterans with fibromyalgia will be compared to asymptomatic veterans for abnormalities in growth hormone and cortisol production.

Thesaurus Terms:
fibromyalgia, neuroendocrine system, syndrome, veteran, cortisol, hypothalamic pituitary axis, military personnel, sign /symptom, somatotropin, steroid, hormone biosynthesis, war /peace, clinical research, human subject

Institution: OREGON HEALTH SCIENCES UNIVERSITY
3181 SW SAM JACKSON PARK RD
PORTLAND, OR 97201
Fiscal Year: 1999
Department: NONE
Project Start: 01-DEC-76
Project End: 30-NOV-99
ICD: NATIONAL CENTER FOR RESEARCH RESOURCES
IRG: CLR

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NEUROTROPHINS AND AN ANIMAL MODEL OF FIBROMYALGIA

Grant Number: 5R01NS039740-03
PI Name: LARSON, ALICE A.
PI Title: PROFESSOR
Project Title: NEUROTROPHINS AND AN ANIMAL MODEL OF FIBROMYALGIA

Abstract: DESCRIPTION (taken from the application): Fibromyalgia syndrome (FMS) is characterized by pain throughout the body (multifocal) with specific areas that are particularly sensitive to pressure. Primary afferent C-fibers are believed to be important in pain transmission. Some C-fibers contain substance P (SP) and are regulated by nerve growth factor (NGF), while others are characterized by the enzyme thiamine monophosphatase (TMPase) and are supported by glial derived neurotrophic factor (GDNF). Consistent with the hypothesis that C-fibers are involved in FMS, the concentrations of SP and NGF in the CSF of these patients are elevated. What initiates this is not known. C-fibers are depolarized by kainic acid, an excitatory amino acid analog. A single i.p. injection of kainic acid increases TMPase stain in the dorsal spinal cord, suggesting sprouting, and produces a persistent (> 12 weeks) decrease in the intensity of mechanical stimulation required to evoke withdrawal responses in rats similar to the lowered threshold of pressure required to produce pain in patients with FMS. Whether kainic acid produces these effects by increasing GDNF or NGF activity along nociceptive pathways is not known. We will test the hypotheses that the mechanical hyperalgesia produced by kainic acid is caused by enhancement of neurotrophic activity that supports C-fibers (NGF and GDNF) which, in turn, enhances proteins associated with these nociceptive pathways. To accomplish this, we will use a rat model (1) to characterize the effect of kainic acid on mechanical nociception using von Frey fibers and grip force; (2) determine whether the content of NGF and GDNF (immunoreactivity) or its receptors (binding) are affected by treatment with kainic acid; (3) to determine whether the application of exogenous NGF or GDNF is sufficient to increase mechanical nociception; (4) to determine whether there is a change in the density of SP- or NkiR immunoreactivity and/or the density of TMPase in the spinal cord or DRG after injection of NGF or GDNF; and (5) to determine whether injection of kainic acid alters either the density of SP- or NKiR-immunoreactivity in the spinal cord or DRG, in a fashion that correlates with its ability to induce mechanical hyperalgesia. These studies will determine whether kainic acid alters neurotrophic activity and nociceptive responses in the rat in a fashion that is consistent with the biochemical and sensory characteristics of FMS. If kainic acid activity proves to be a useful model of FMS, therapeutic options may be more readily developed for this disease.

Thesaurus Terms: disease /disorder model, fibromyalgia, hyperalgesia, model design /development, neurotrophic factor C fiber, growth factor receptor, kainate, phosphomonoesterase, spinal ganglion, substance P, thiamine injection /infusion, laboratory rat

Institution:
Fiscal Year: 2001
Department:
Project Start:
Project End:
ICD: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
IRG:

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AUTONOMIC STRESS REACTIVITY IN FIBROMYALGIA
Grant Number: 1R21AR46077-01
PI Name: OKIFUJI, AKIKO
PI Title:
Project Title: AUTONOMIC STRESS REACTIVITY IN FIBROMYALGIA

Abstract:
This is an R21 application proposing to conduct a preliminary study on the relationship between autonomic stress-reactivity and pain sensitivity in patients with fibromyalgia syndrome (FMS). Although the exact pathphysiologic mechanisms of FMS are yet to be determined, FMS is generally considered as a disorder involving dysregulated central pain modulation. In addition, FMS seems to be associated with dysfunctional stress adaptation. Many FMS patients report that stress exacerbates their pain and symptoms. Research has suggested that autonomic dysregulation exists in FMS. FMS patients tend to exhibited blunted autonomic reactivity to noise, cold, and physical stressors. Research in cardiovascular and headache disorders, as well as animal/human laboratory studies, have demonstrated the antinociceptive effects of increased arousal, particularly baroreflex and occulosympathetic reactivity. These previous reports suggest that dysregulated autonomic functions in response to stressors play an important role in elevated pain sensitivity and other FMS symptoms.

In the proposed study, we hypothesize that

1) FMS is associated with blunted sympathetic reactivity,

2) FMS is related to increased susceptibility to develop orthostatic intolerance, and

3) stress-induced analgesics are minimized in FMS.

30 FMS patients, 30 patients with temporomandibular disorder (TMD: localized pain control), and pain-free healthy subjects will undergo various stress tasks, orthostatic torelance test, and pain sensitivity test while blood pressure and pupil size are continuously measured. The levels of stress associated with tasks are relatively moderate (mental arithmetic, discussion of stressful experience), thereby allowing us to determine the importance of daily stressors patients report as an aggravating factor. Results from this study thus should provide initial evidence regarding the effects of stress-induced dysautonomia in FMS symptoms. Furthermore, the results of the study may provide an important avenue for improving those symptoms secondary to autonomic dysfunction.

Thesaurus Terms:
autonomic reflex, fibromyalgia, pain threshold, stress, temporomandibular joint syndrome, analgesia, baroreflex, blood pressure, pathologic process, postural hypotension, clinical research, female, human subject

Institution: UNIVERSITY OF WASHINGTON
3935 UNIVERSITY WAY NE
SEATTLE, WA 98195
Fiscal Year: 1999
Department: ANESTHESIOLOGY
Project Start: 01-JUL-99
Project End: 30-JUN-02
ICD: NAT INST OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES
IRG: ZAR1

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AUDITORY WORKING MEMORY IN CFS--AN FMRI STUDY
Grant Number: 1R01MH57272-01A1
PI Name: LANGE, GUDRUN
PI Title:
Project Title: AUDITORY WORKING MEMORY IN CFS--AN FMRI STUDY

Abstract:
There is no text on file for this abstract.

Thesaurus Terms:
chronic fatigue syndrome, cognition disorder, functional magnetic resonance imaging, memory disorder, mental disorder diagnosis, neuropsychology, noninvasive diagnosis, short term memory, auditory cortex, brain mapping, mathematical model, performance, behavioral /social science research tag, bioimaging /biomedical imaging, clinical research, human subject, positron emission tomography

Institution: UNIVERSITY OF MEDICINE & DENTISTRY OF NJ
30 BERGEN ST
NEWARK, NJ 07107
Fiscal Year: 1999
Department: PSYCHIATRY
Project Start: 01-JAN-99
Project End: 31-DEC-01
ICD: NATIONAL INSTITUTE OF MENTAL HEALTH
IRG: ZRG5

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MUSCLE BLOOD FLOW AND CHRONIC FATIGUE SYNDROME
Grant Number: 1R01HL65179-01
PI Name: MCCULLY, KEVIN K.
PI Title:
Project Title: MUSCLE BLOOD FLOW AND CHRONIC FATIGUE SYNDROME

Abstract:
There is no text on file for this abstract.

Thesaurus Terms:
blood flow, chronic fatigue syndrome, muscle metabolism, exercise, hemodynamics, ischemia, oxygen consumption, clinical research, human subject, nuclear magnetic resonance spectroscopy, ultrasound blood flow measurement

Institution: UNIVERSITY OF GEORGIA
ATHENS, GA 30602
Fiscal Year: 1999
Department: EXERCISE SCIENCE
Project Start: 25-SEP-99
Project End: 31-AUG-03
ICD: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
IRG: ZRG1

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VENOUS DYSFUNCTION IN CHRONIC FATIGUE SYNDROME
Grant Number: 1R03AI45954-01
PI Name: STEWART, JULIAN M.
PI Title:
Project Title: VENOUS DYSFUNCTION IN CHRONIC FATIGUE SYNDROME

Abstract:
There is no text on file for this abstract.

Thesaurus Terms:
blood flow, blood vessel disorder, blood volume, chronic fatigue syndrome, blood pressure, heart rate, phenylephrine, syncope, vascular resistance, adolescence (12-18), blood flow measurement, clinical research, human subject

Institution: NEW YORK MEDICAL COLLEGE
ELMWOOD HALL
VALHALLA, NY 10595
Fiscal Year: 1999
Department: PEDIATRICS
Project Start: 25-SEP-99
Project End: 31-AUG-02
ICD: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
IRG: ZRG1

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