NIH GUIDE, Volume 21, Number 41, November 13, 1992

PA:  PA-93-019

P.T. 34


  Neurological Disorders 




  Disease Prevention+ 

  Risk Factors/Analysis 

National Institute of Neurological Disorders and Stroke


The Division of Stroke and Trauma (DST), National Institute of

Neurological Disorders and Stroke (NINDS), invites applications for

support of research that will increase our understanding of the causes

of, and add to our ability to treat and prevent, recurrent headache,

especially migraine.


Applications may be submitted by foreign and domestic institutions,

for-profit and non-profit organizations, public or private, such as

universities, colleges, hospitals, laboratories, units of state and

local governments, and eligible agencies of the Federal government.

Foreign institutions are eligible to apply for research project grants

(R01) only.  Foreign institutions are not eligible for First

Independent Research Support and Transition (FIRST) (R29) awards.

Applications from minority institutions, minority individuals, and

women are particularly encouraged.


The support mechanisms for grants in this area will be the traditional

investigator-initiated research project grant (R01), the FIRST award

(R29), the program project grant (P01), and the center grant (P50).  As

consistent with the aforementioned mechanisms, the Principal

Investigator or program director, as well as any participating

investigators, will plan, direct, and perform the research.  Applicants

for program project grants should contact the NINDS representative

listed below as early as possible in the planning stages.



Millions of Americans suffer from recurrent headaches.  For many, the

headaches are of such severity that they are disabling.  In addition to

the profound effects on the quality of life for these people, the

economic consequences are enormous.  Some estimates are that headache

sufferers seek medical care through over eight million visits to

physicians or emergency rooms each year.  Other estimates of the impact

of this condition are that migraineurs alone lose over sixty million

workdays a year.  A major research goal of the NINDS, which is the

responsible agency for neurological research in the Federal Government,

is to understand the basic pathophysiology of headaches and to use this

understanding to improve methods for treatment and prevention of


Headaches can be classified as vascular headaches, muscle contraction

headaches, tension headaches, or inflammatory headaches, to mention but

a few.  Vascular headaches are thought to involve abnormal function of

the brain's blood vessels or vascular system.  The most common type of

vascular headache is migraine headache, the cause of which is still not

known.  Migraine headaches are frequently characterized by severe pain

on one or both sides of the head, nausea, and extreme sensitivity to

light and noises.  The two most prevalent types of migraine headache

are the classic migraine and the common migraine.  The major difference

between these two types of migraine is that the victim of a classic

migraine experiences an aura about 10 to 30 minutes before the onset of

headache.  This aura is the major prodromal neurological symptom and

warning of the imminent onset of the classic migraine.  The pain of a

migraine headache is described as an intense, throbbing, or pounding

pain in the forehead, temple, ear, jaw, or around the eye; these pains

may continue for several days.  The common migraine is not preceded by

an aura; however, some people who are subject to the common migraine

exhibit a variety of vague symptoms before the onset of the headache,

such as mood shifts, fatigue, and abnormal retention of fluids.  The

pain of common migraine can also last several days, during which the

victim may have nausea or vomiting.

Research Goals and Scope

Examples of investigator-initiated research grant applications for

basic and clinical studies related, in the broadest sense, to the

etiology, prevention, and treatment of recurrent headache, especially

migraine headache, may include, but should not necessarily be limited


o  precise elucidation of the cellular and molecular events that cause

or lead to headaches;

o  development of more specific clinical interventions for both

prevention and treatment of migraine headaches, such as anti-platelet

clumping drugs; more efficacious anti-serotonin drugs or other means of

preventing or reducing the constriction of arteries; and site-specific


o  development of methods for precisely identifying the sequence of

alterations in blood flow or vascular reactivity that may be an

initiating factor for migraine;

o  identification of risk factors, or events, that predispose the

migraineur to an attack, such as stress, allergies, diet, sleeping

patterns, neuroses, personality type, and behavioral characteristics

such as excitability and compulsiveness;

o  control of risk factors in relation to the prevention of a migraine


o  longitudinal epidemiology of the distribution and inter-relation

between risk factors and the predisposition to an attack of migraine


o  determination of whether or not genetic factors predispose to

migraines, and, if so, identification of the genetic locus with a view

toward understanding the causative or contributory mechanisms and

developing a means of preventing migraine headache; and

o  determination of the relation between hormones and migraine.



NIH policy is that applicants for NIH clinical research grants and

cooperative agreements will be required to include minorities and women

in study populations so that research findings can be of benefit to all

persons at risk of the disease, disorder, or condition under study;

special emphasis should be placed on the need for inclusion of

minorities and women in studies of diseases, disorders, and conditions

that disproportionately affect them.  This policy is intended to apply

to males and females of all ages.  If women or minorities are excluded

or inadequately represented in clinical research, particularly in

proposed population-based studies, a clear compelling rationale should

be provided.

The composition of the proposed study population must be described in

terms of gender and racial or ethnic group. In addition, gender and

racial or ethnic issues should be addressed in developing a research

design and sample size appropriate for the scientific objectives of the

study.  This information should be included in the form PHS 398 in

Sections 1-4 of the Research Plan AND summarized in Section 5, Human

Subjects.  Applicants are urged to assess carefully the feasibility of

including the broadest possible representation of minority groups;

however, the NIH recognizes that it may not be feasible or appropriate

in all research projects to include representation of the full array of

Unites States racial or ethnic minority populations:  Native Americans

(including American Indians or Alaska Natives), Asian or Pacific

Islanders, Blacks, and Hispanics).  The rationale for studies on single

minority population groups should be provided.

For the purpose of this policy, clinical research includes human

biomedical and behavioral studies of etiology, epidemiology, prevention

(and prevention strategies), diagnosis, or treatment of diseases,

disorders, or conditions, including, but not limited to, clinical


The usual NIH policies concerning research on human subjects also

apply.  Basic research or clinical studies in which human tissues

cannot be identified or linked to individuals are excluded; however,

every effort should be made to include human tissues from women and

racial or ethnic minorities when it is important to apply the results

of the study broadly.  This directive should be addressed by


For foreign awards, the policy on inclusion of women applies fully.

Since the definition of minority differs in other countries, the

applicant must discuss the relevance of research involving foreign

population groups to the United States' population, including


If the required information is not contained within the application,

the review will be deferred until the information is provided.

Peer reviewers will address specifically whether the research plan in

the application conforms to these policies.  If the representation of

women or minorities in a study design is inadequate to answer the

scientific question(s) addressed AND the justification for the selected

study population is inadequate, it will be considered a scientific

weakness or deficiency in the study design and will be reflected in

assigning the priority score to the application.

All applications for clinical research submitted to the NIH are

required to address these policies.  NIH funding components will not

award grants or cooperative agreements that do not comply with these



Applications are to be submitted on the grant application form PHS 398

(rev. 9/91) according to the instructions included in the application

package.  These application packages are available at the offices of

sponsored research of most institutions eligible to receive Federal

grants and from the Office of Grants Inquiries, Division of Research

Grants, National Institutes of Health, Westwood Building, Room 449,

Bethesda, MD 20892, telephone (301) 496-7441.

Applicants for program project grants should request, from the address

below, a copy of the NINDS Guidelines: Program Project and Research

Center Grants (rev. June 1992). Receipt dates for new research project

grant applications and FIRST Awards (R01 and R29, respectively) and for

program project and center grant applications (P01 and P50,

respectively) are February 1, June 1, and October 1.

FIRST award applications must include at least three sealed letters of

reference attached to the face page of the original application.  FIRST

award applications submitted without the required number of reference

letters will be considered incomplete and will be returned without


On page 1 of form PHS 398, check "yes" in Item 2a, enter the number of

this Program Announcement in the space provided, and provide the name

of this Program Announcement (Neurological Basis of Recurrent

Headaches, Especially Migraine) in the blank space labeled "Title."

Use the mailing label provided in the application package to mail the

signed original and five exact copies to the Division of Research

Grants.  If the application is for a program project or center grant,

please send the original and three copies to the Division of Research

Grants.  An additional two copies of the program project or center

grant application sent to the address below would be useful for

expediting the processing of these applications for multidisciplinary



Research project grant applications and FIRST award applications (R01

and R29, respectively) will be reviewed for scientific and technical

merit by an appropriate study section in the Division of Research

Grants.  Program project grant and center grant applications (P01 and

P50, respectively) will be reviewed according to the practice of the

Institute to which the application is assigned.  The second level of

review will be by the appropriate National Advisory Council.  The

standard review criteria will be used to assess the scientific merit of



Applications will compete for available funds with all other

applications. The following will be considered when making funding


o  quality of the proposed projects as determined by peer review

o  availability of funds

o  program balance among research areas


Questions concerning scientific aspects of this PA may be addressed to:

Dr. George N. Eaves

Division of Stroke and Trauma

National Institute of Neurological Disorders and Stroke

Federal Building, Room 8A13

Bethesda, MD  20892

Telephone:  (301) 496-4226

FAX:  (301) 480-1080

Questions concerning fiscal aspects of this PA may be addressed to:

Ms. Kathleen Howe

Division of Extramural Activities

National Institute of Neurological Disorders and Stroke

Federal Building, Room 1004

Bethesda, MD  20892

Telephone:  (301) 496-9231

FAX:  (301) 402-0219


This program is described in the Catalogue of Federal Domestic

Assistance, No. 93.853, Clinical Research Related to Neurological

Disorders, and 93.854, Biological Basis Research in the Neurosciences.

Grants will be awarded under the authority of the Public Health Service

Act, Title IV, Section 301 (Public Law 78-410, as amended:  42 USC 241)

and administered under PHS grants policies and Federal Regulations 42

CFR Part 52 and 45 CFR 74.  This program is not subject to Health

Services Agency review of the intergovernmental review requirements of

Executive Order 12372.


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