Full Text PA-97-059
NIH GUIDE, Volume 26, Number 16, May 16, 1997
PA NUMBER:  PA-97-059
P.T. 34

  Musculoskeletal System 
  Disease Prevention+ 

National Institute of Arthritis and Musculoskeletal and Skin Diseases
National Institute of Child Health and Human Development
National Institute of Neurological Disorders and Stroke
National Institute for Occupational Safety and Health
This initiative invites applications directed to the study of the
pathogenesis, epidemiology, prevention, and treatment of repetitive
motion disorders.
The Public Health Service (PHS) is committed to achieving the health
promotion and disease prevention objectives of "Healthy People 2000,"
a PHS-led national activity for setting priority areas.  This PA,
Repetitive Motion Disorders, is related to the priority area of
chronic disabling conditions.  Potential applicants may obtain a copy
of "Healthy People 2000" (Full Report:  Stock No. 017-001-00474-0 or
Summary Report:  Stock No. 017-001-00473- 1) through the
Superintendent of Documents, Government Printing Office, Washington,
DC 20402-9325 (telephone 202-512-1800).
Applications may be submitted by foreign and domestic, for-profit and
non-profit organizations, public and private, such as universities,
colleges, hospitals, laboratories, units of State and local
governments, and eligible agencies of the Federal government.
Foreign institutions or organizations in foreign countries are not
eligible for First Independent Research Support and Transition
(FIRST) (R29) awards.  Applications from minority individuals, women,
and persons with disabilities are encouraged.
The support mechanisms for grants in this area will be the individual
investigator-initiated research grant (R01) and the First Independent
Research Support and Transition (FIRST) Award (R29).
Applicants or collaborators from institutions that have a General
Clinical Research Center (GCRC) funded by the National Center for
Research Resources may wish to identify the GCRC as a resource for
conducting the proposed research.  If so, a letter of agreement from
the GCRC program director should be included with the application.
The words "repetitive motion disorder" describe a constellation of
conditions that primarily affect the soft tissues, including the
nerves (e.g., carpal tunnel syndrome), tendons (e.g., tenosynovitis,
peritendinitis, epicondylitis), and muscles (e.g., tension neck
syndrome).  These conditions are common, are often insidious in their
onset, and may or may not have relatively clear diagnostic criteria.
In addition, their etiologies are often multifactorial,  with work
activities often contributing significantly, but not solely, to their
development or exacerbation.  This relationship to work is
significant.  In 1992, 60% of new occupational illnesses were
associated with repetitive motion.  The national rate of reported
repetitive motion disorders has increased 880%, from 5 cases per
10,000 workers in 1982 to 44 cases per 10,000 workers in 1992.  The
highest rates generally occur in industries with a substantial amount
of repetitive work (e.g., meat and poultry processing, automobile
manufacturing).  Recently, the Bureau of Labor Statistics has
reported  an increase in repetitive motion disorders in "safe
industries", such as data entry jobs using a computer.
Despite the increasing prevalence of these disorders, and the fact
that they have become an extremely costly public health problem,
there are important gaps in our knowledge as relates to the
pathophysiology and etiology of repetitive motion disorders.  In
addition, there is uncertainty regarding the optimal methods to
diagnose, treat, and prevent them.
The current Program Announcement (PA) represents a continued interest
in repetitive motion disorders, and is the direct outgrowth of an
NIAMS and American Academy of Orthopaedic Surgeons sponsored workshop
on the status and future research directions on Repetitive Motion
Disorders of the Upper Extremity, held in June 1994.  A primary
objective of the workshop was to develop suggestions for future
research directions in the pathogenesis, treatment, and prevention of
repetitive motion disorders.  A more detailed description of the
proceedings and suggested research topics is available in Repetitive
Motion Disorders of the Upper Extremity, edited by S. L. Gordon, S.
J. Blair, and L. J. Fine, American Academy of Orthopaedic Surgeons,
Chicago, 1995.
Through the use of this PA, the NIAMS, the NICHD, the NINDS, and the
NIOSH anticipate the receipt of a broad range of applications
targeted, but not limited, to the following areas:
(1) Pathophysiology:  Biomechanical Loads
o  Develop and validate methods and models for predicting structural
changes in soft tissues based on external exposure.
o  Develop and validate methods for measuring biomechanical and
biochemical changes in soft tissue.
o  Compare the biologic and healing response of tissues to acute
loading versus chronic loading.
o  Identify thresholds of physiologic injury to soft tissue under
repetitive loading conditions.
o  Develop models for specific musculoskeletal disorders.
(2) Pathophysiology:  Connective Tissue
o  Study the structure-function relationships of human tendons and
o  Determine the components of tendon that detect and resist load.
o  Investigate the innervation of tendons.
o  Elucidate the mechanisms by which cells perceive and respond to
mechanical stimulation and loads.
o  Define the structure, composition, and pathology of the
fibrocartilaginous regions of tendon (includes fibrocartilage
development and how associated with tendon pathology).
o  Study the effects of repetitive motion on synovium.
o  Develop an animal model for investigating the effects of
repetitive use and overuse of tendons, ligaments, and synovium.
o  Investigate the influence of age, gender, and genetics on the
development of repetitive motion disorders.
o  Develop diagnostic criteria to distinguish between painful
musculoskeletal syndromes having no physical findings and those with
a structural mechanism.
(3) Pathophysiology:  Muscle
o  Evaluate the relationship among cognitive/attention demands,
muscle activity, and pathophysiology in patients and controls with
disorders associated with repetitive motion.
o  Evaluate the relationship between localized fatigue, discomfort,
perceived exertion, and muscular disorders.
o  Define the acute and chronic injury mechanisms in skeletal muscle.
o  Define the role, if any, of altered muscle fiber recruitment
patterns in repetitive motion disorders.
o  Define the conditioning methods required to prevent muscle injury.
o  Determine clinical indicators of muscle dysfunction.
o  Determine which systemic and/or muscle tissue factor(s) limit the
rate and degree of recovery following an overuse injury.
(4) Pathophysiology:  Nerve
o  Develop and validate a peripheral nerve compression model as
related to mechanical issues (i.e., extrinsic pressure).
o  Explore changes in central neuronal function in repetitive motion
o  Characterize nerve damage in  repetitive motion disorders (e.g.,
what role do growth factors play here, and how does the presence of
certain neurochemicals relate to the presence of the persistent pain
associated with these disorders.
o  Better understand the biochemical and other mechanisms that lead
to sensitization of nociceptors in deep tissue, with resultant
hyperalgesia (could lead to novel therapeutic approaches for deep
(6) Clinical Issues
o  Define more clearly which physical tests and diagnostic
evaluations (e.g.,  sensibility testing, electrodiagnostic studies,
and imaging studies) should be performed, and at what stage of
disease progression.
o  Develop improved electrodiagnostic, clinical, and other diagnostic
tools for soft-tissue disorders of the upper limb.
o  Determine the roles of ergonomic and workstation changes and
exercise regimens, in prevention.
o  Determine the value of drug treatment (including NSAIDs),
physical/occupational/ manipulative therapies, rest/immobilization,
injection, other common non-operative treatments, and surgery, in the
clinical management of repetitive motion injuries.
o  Determine which work and recreational activities are safe
following treatment, and when it is appropriate to return to them.
o  Determine the incidence of repetitive motion disorders and value
of treatments in persons with pre-existing severe disability (e.g.,
brain injury, stroke, spinal cord injury, amputation, cerebral
No priority has been established among the research suggestions
presented.  Applications are encouraged in any scientifically
meritorious research area related to the pathogenesis, treatment, or
prevention of repetitive motion disorders.  Research applications are
encouraged from all basic science disciplines pertinent to this area,
as well as the medical specialties providing health care for these
patients, including, but not limited to:  orthopaedic and
neurosurgeons, occupational medicine physicians, internists and
family practitioners, rheumatologists, physiatrists, chiropractic and
osteopathic practitioners, and occupational and physical therapists.
It is the policy of the NIH that women and members of minority groups
and their subpopulations must be included in all NIH supported
biomedical and behavioral research projects involving human subjects,
unless a clear and compelling rationale and justification is provided
that inclusion is inappropriate with respect to the health of the
subjects or the purpose of the research.  This policy results from
the NIH Revitalization Act of 1993 (Section 492B of Public Law
All investigators proposing research involving human subjects should
read the "NIH Guidelines for Inclusion of Women and Minorities as
Subjects in Clinical Research," which have been published in the
Federal Register of March 28,1994 (FR 59 14508-14513), and reprinted
in the NIH Guide for Grants and Contract, Volume 23, Number 11, March
18, 1994.
Applications are to be submitted on the grant application form PHS
398 (rev. 5/95) and will be accepted at the standard application
deadlines as indicated in the application kit.  Applications kits are
available at most institutional offices of sponsored research and may
be obtained from the Division of Extramural Outreach and Information
Resources, National Institutes of Health, 6701 Rockledge Drive, MSC
7910, Bethesda, MD 20892-7910, telephone 301/710-0267, email:
ASKNIH@odrockm1.od.nih.gov. The title and number of the program
announcement must be typed in Section 2 on the face page of the
Applications for the FIRST Award (R29) must include at least three
sealed letters of reference attached to the face page of the original
application.  FIRST Award (R29) applications submitted without the
required number of reference letters will be considered incomplete
and will be returned without review.
The completed original application and five legible copies must be
sent or delivered to:
6701 ROCKLEDGE DRIVE, ROOM 1040 - MSC 7710
BETHESDA, MD  20892-7710
BETHESDA, MD  20817 (for express/courier service)
Upon receipt, applications will be reviewed for completeness by the
DRG.  Incomplete applications will be returned to the applicant
without further consideration.
Applications will be assigned on the basis of established Public
Health Service referral guidelines. Applications will be reviewed for
scientific and technical merit by  an appropriate peer review group
convened in accordance with NIH peer review procedures.  As part of
the initial merit review, all applications will receive a written
critique and may undergo a process in which only those applications
deemed to have the highest scientific merit, generally the top half
of all applications under review, will be discussed, assigned a
priority score, and receive a second level review by the appropriate
national advisory council or board.
Review Criteria
o  Scientific, technical, or medical significance and originality of
proposed research;
o  Appropriateness and adequacy of the experimental approach and
methodology proposed to carry out the research;
o  Qualifications and research experience of the Principal
Investigator and staff, particularly, but not exclusively, in the
area of the proposed research;
o  Availability of the resources necessary to perform the research;
o  Appropriateness of the proposed budget and duration in relation to
the proposed research; and
o  Adequacy of plans to include both genders and minorities and their
subgroups as appropriate for the scientific goals of the research.
Plans for the recruitment and retention of subjects will also be
The Initial Review Group will also examine the provisions for the
protection of human subjects and animal welfare and the safety of the
research environment.
Applications will compete for available funds with all other approved
applications assigned to NIAMS and NINDS.  The following will be
considered in making funding decisions:
o  Quality of the proposed project as determined by peer review
o  Availability of funds
o  Program relevance and balance among research areas of the
Written and telephone inquiries are encouraged.  The opportunity to
clarify any issues or questions from potential applicants is welcome.
For scientific programmatic inquiries contact:
James S. Panagis, M.D., M.P.H.
Orthopaedics Program
National Institute of Arthritis and Musculoskeletal and Skin
Diseases, NIH
Natcher Building, Room 5AS-37K
45 Center Drive, MSC 4500
Bethesda, MD  20892-6500
Telephone: (301) 594-5055
FAX: (301) 480-4543
Email:  panagisj@ep.niams.nih.gov
Stephen M. Tuel, MSE, MD
National Center for Medical and Rehabilitation Research
National Institute of Child Health and Human Development, NIH
Building 61E, Room 2A03
Bethesda, MD  20892-7510
Telephone:  (301) 402-2242
FAX:  (301) 402-0832
Email:  tuels@hd01.nichd.nih.gov
Paul L. Nichols, Ph.D.
National Institute of Neurological Disorders and Stroke
Federal Building, Room 504
Bethesda, MD  20892
Telephone:  (301) 496-1431
FAX:  (301) 402-2060
Email:  pn13w@nih.gov
Larry Fine, MD, DrP.H.
Division of Surveillance, Hazard Evaluations and Field Studies
National Institute for Occupational Safety and Health, CDC
4676 Columbia Parkway, Mail Stop R-12
Cincinnati, OH  45226-1998
Telephone:  (513) 841-4428
FAX: (513) 841-4483
Direct inquiries regarding fiscal matters to:
Vicki Maurer
Grants Management Branch
National Institute of Arthritis and Musculoskeletal and Skin Diseases
Natcher Building, Room 5AS-49A
45 Center Drive, MSC 4500
Bethesda, MD  20892-6500
Telephone:  (301) 594-3504
FAX:  (301) 480-5450
Email:  maurerv@ep.niams.nih.gov
Mary Ellen Colvin
Grants Management Branch
National Institute of Child Health and Human Development, NIH
Building 61E, Room 8A017
Bethesda, MD  20892-7510
Telephone:  (301) 496-1303
FAX:  (301) 402-0915
E-mail:  colvinm@hd01.nichd.nih.gov
Dawn Richardson
Grants Management Branch
National Institute of Neurological Disorders and Stroke
Federal Building, Room 1004
Bethesda, MD  20892
Telephone:  (301) 496-9231
FAX:  (301) 401-0219
Email:  da8h@nih.gov
Roy Fleming
Grants Management Branch
National Institute for Occupational Safety and Health, CDC
1600 Clifton Road, N.E., Building 1
Mail Stop D30
Atlanta, GA  30333
Telephone:  (404) 639-2810
FAX:  (404) 639-2196
Email:  RMF2@CDC.GOV
Awards made in this program are described in the Catalog of Federal
Domestic Assistance:  No. 93.846, Arthritis, Musculoskeletal and Skin
Diseases Research, No. 98.853, Clinical Research Related Neurological
Disorders, and No. 93.854, Biological Basic Research in the
Neurosciences.  Awards will be made under the authority of the Public
Health Service Act, Title III, Section 301 (Public Law 410, 78th
Congress, as amended, 42 USC 241) and administered under PHS grant
policies and Federal regulations 42 CFR Part 52 and 45 CFR Part 74.
This program is not subject to intergovernmental review requirements
of Executive Order 12372 or Health Systems Agency review.
The PHS strongly encourages all grant and contract recipients to
provide a smoke-free workplace and promote the non-use of all tobacco
products.  In addition, Public Law 103-227, the Pro-Children Act of
1994, prohibits smoking in certain facilities (or in some cases, any
portion of a facility) in which regular or routine education,
library, day care, health care or early childhood development
services are provided to children.  This is consistent with the PHS
mission to protect and advance the physical and mental health of the
American people.

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