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Release Date:  November 27, 1998 (see replacement PA-03-152)

PA NUMBER:  PA-99-021


National Institute of Nursing Research
National Institute of Dental and Craniofacial Research
National Institute on Aging
National Institute of Arthritis and Musculoskeletal and Skin Diseases
National Cancer Institute
National Institute of Child Health and Human Development
National Institute on Drug Abuse
National Heart, Lung, and Blood Institute
National Institute of Mental Health
National Institute of Neurological Disorders and Stroke
National Center for Complementary and Alternative Medicine

This program announcement replaces PA-95-056, which was published in the NIH
Guide, Vol 24, No. 15, April 28, 1995.


The purpose of this biobehavioral pain research program announcement (PA) is to
inform the scientific community of the interests of the various institutes at the
National Institutes of Health (NIH) and to stimulate and foster a wide range of
basic and clinical studies on pain as they relate to the missions of these

Applications are encouraged to study individual differences in pain responses
which may be due to factors such as genetic differences, endocrine activity,
neural activity, immune function, psychological state, disability state, age,
gender, and cultural background.  Research is also needed in areas such as
understanding the neuroanatomical pathways and the neurophysiological mechanisms
in pain.  The pain experience needs to be examined at all levels of research
including the gene, molecule, cell, organ, and individual with the goal of
developing biobehavioral interventions to manage or prevent pain.


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 Program Announcement (PA),
Biobehavioral Pain Research, is related to the priority areas of chronic
disabling conditions, cancer, and clinical prevention services.  Potential
applicants may obtain a copy of "Healthy People 2000" at


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.  Racial/ethnic minority individuals, women, and persons with
disabilities are encouraged to apply as principal investigators.


This PA will use the National Institutes of Health (NIH) research project grant
(R01) award mechanism.  Responsibility for the planning, direction, and execution
of the proposed project will be solely that of the applicant.  The total project
period for an application submitted in response to this PA may not exceed five


Pain is a critical national health problem.  It is the most common reason for
medical appointments, nearly 40 million visits annually, and costs this country
over $100 billion each year in health care and lost productivity.  Pain has a
profound effect on the quality of human life.  In addition to possible
deleterious effects on immune function, pain can cause disruptions in sleep,
eating, mobility, and overall functional status.  In the hospitalized patient,
pain may be associated with increased length of stay, longer recovery time, and
poorer patient outcomes, all of which have health care quality and cost

Progress is being made in understanding the neuroanatomical pathways and the
neurophysiological and neurochemical mechanisms involved in pain.  However,
understanding the subjective pain experience in individuals presents unique
scientific challenges.  Even though the basic physiology may be similar, people
react in very different ways, perhaps due to genetic differences, endocrine
activity, neural activity, immune function, stress, psychological state, age,
gender, and cultural background.  Thus, the pain experience needs to be examined
at all levels of basic and clinical research, including the gene, molecule, cell,
organ, and individual, with the goal of developing biobehavioral interventions
to manage or prevent pain.

In order to develop a research agenda, ten NIH institutes sponsored a workshop,
"Biobehavioral Pain Research: A Multi-Institute Assessment of Cross-Cutting
Issues and Research Needs," in January 1994.  This meeting, under the aegis of
the NIH Health and Behavior Coordinating Committee, resulted in the
identification of research needs from a broad spectrum of the scientific
community expert in pain research.

The following pain research areas cut across Institutes and programs and should
not be viewed as restricted to only one specific Institute.  Current NIH referral
guidelines will be used to assign grant applications to the most appropriate NIH
Institute based on the scientific focus of the application.

The following topics and study areas are not intended to be comprehensive or

Understanding Critical Interfaces Between Biology and Behavior

o  Explore the neural basis of pain perception and discover targets in the signal
transduction pathways that may be the most effective points for interventions in
the control of pain across the lifespan.

o  Examine the neuroendocrine and immunological correlates of pain.

o  Investigate both pharmacological and behavioral interventions to prevent pain.

o  Refine neuroimaging algorithms for the study of structural and functional
correlates of pain perception.

o  Conduct animal and human studies on the temporal patterning of pain.

o  Explore the basic developmental aspects of pain processing, including an
integration of psychological, neurochemical, and molecular approaches which could
impact the treatment of pain across the life span.

o  Identify genes relevant to pain and pain inhibitory mechanisms.

o  Examine the role of placebo effect in pain treatment.

Pain, Suffering, and Emotion

o  Explore basic mechanisms of the conscious perception of pain and the affective
responses to pain.

o  Examine the relative importance of biological, socioenvironmental, and
psychological variables in explaining variations in pain-expressive behaviors.

o  Clarify the relationship between depression and chronic pain by elucidating
the biological factors, characteristics of the pain (e.g., location, quality,
timing), environmental circumstances, and personal characteristics that are
predictive of this relationship.

o  Elucidate emotions and emotional disturbances, in addition to depression,
(e.g., anger, fear, anxiety) which are associated with acute and chronic pain
conditions, and determine how these emotions modify the experience of pain.

Pain and Behavior

o  Explore the sensory, cognitive, and affective aspects of acute and chronic
pain across the lifespan.

o  Elucidate the interaction of biological markers, central nervous system
mechanisms, and drug and behavioral interventions.

o  Determine the relative contributions of biological, psychological, behavioral,
and environmental predictors of the course of pain, pain dysfunction, and
response to treatment for pain.

o  Examine addiction risk in patients taking controlled drugs for pain;  the role
of tolerance, addiction and dependence in the consumption of these drugs; and
implications of long-term use in noncancer disease states.

o  Develop and refine biobehavioral techniques for optimizing adherence to pain

Behavior-Related Interventions

o  Evaluate research strategies to integrate medical, nursing, dental,
neurological, pharmacological, and behavioral treatments for pain problems. 
Compare the relative effectiveness of each mode of treatment, and combined
treatments, and their potentiating effects on multiple outcomes, such as pain,
physical functioning, psychological functioning, health care utilization, and

o  Conduct research on the mechanisms and process variables that are responsible
for the efficacy of behavioral interventions.  This research includes studies to
understand better the effect of patients' expectations and beliefs,
psychophysiological states (e.g., anxiety, relaxation, stress), adherence, and
specific cognitive (e.g., imagery) and social (e.g., support) components in
behavioral interventions.

o  Determine which behavioral treatments are most effective for specific
subgroups of patients differentiated by factors such as age, gender, race, ethnic
group, level of dysfunction, or psychosocial characteristics.

o  Conduct clinical trials of cognitive/behavioral pain control methods and
combinations of medical, pharmacological, and cognitive/behavioral pain control

o  Compare the costs of various types of interventions for pain, including
economic analyses of pain, pain dysfunction, and pain treatments with different
and combined biomedical and biopsychosocial models of treatment.

o  Investigate the effectiveness and appropriate targeting of alternative
treatments (e.g., hypnosis, massage, spinal manipulations, acupuncture) using
randomized, controlled trials of these treatments in association with
conventional medical approaches.

o  Assess methods for primary, secondary, and tertiary prevention of pain.

o  Establish dose-response curves for biobehavioral interventions.

o  Test interventions to improve health care practice in such areas as pain
assessment, analgesic management, pain prevention, and rehabilitation.

Commonalities and Differences in Pain Expression, Experience, and Treatment

o  Study cognitive factors in the experience of pain, disability, and pain
behaviors across disorders, including such factors as self-efficacy, perceived
control, and pain beliefs.

o  Establish the factors that prevent a person with acute pain from developing
a chronic pain problem and a chronic pain- related disability.  Areas to assess
include patient biological/organic, psychosocial, and socioeconomic
characteristics, interactions of the patient with health care providers, family
and social supports, and workplace factors.

o  Refine existing techniques for measuring pain and develop new techniques that
are disease- and outcome-specific for different populations.

o  Determine the supraspinal mechanisms of pain modulation, determine the effects
of specific pain treatments on these central nervous system processes, and apply
new findings on CNS plasticity to the understanding of pain.

o  Examine the interrelationships between pain and other symptoms and
comorbidities (e.g., fatigue, sleep alterations, nausea, vomiting, anxiety, mood
disorders, physical deconditioning, stress).

Pain in Special Populations

o  Test culturally sensitive approaches to pain assessment and management,
including translation of the instruments into foreign languages and validation
as needed.

o  Investigate biobehavioral pain treatments for special populations including
infants, children, elderly, cognitively impaired, ethnic minority groups,
substance abusers with pain disorders, and individuals with disabilities.

o  Determine effective biobehavioral interventions for HIV- and AIDS-related
pain, as well as the pain prevalence, scope, and severity of patients who are
HIV-infected.  Explore alterations in nociceptive mechanisms and pain perception
in patients with HIV.

o  Investigate the roles of sleep and circadian variation in the precipitation
and modulation of pain in populations who have special rest - activity needs such
as infants, children, elderly, pregnant women, night-shift workers.  This
research could include studies of the effect of pain and its pharmacological
treatment on sleep and daytime alertness, as well as the effects of disturbed
sleep on pain and pain perception.  Studies of seasonal and other variations are
also appropriate.

o  Test and evaluate pharmacotherapies and behavioral treatments in patients with
current and past histories of addiction, including infants born to drug-,
alcohol-, and tobacco-dependent mothers, and HIV-infected persons.

o  Investigate the effectiveness of biobehavioral pain management in terminally
ill and dying patients.

o  Study the interrelationship of Axis II, as well as Axis I, psychiatric
disorders (e.g., borderline personality, histrionic, antisocial) and chronic
pain, and relate these findings to pharmacological and behavioral therapies.

o  Determine gender-related differences in the pain experience, such as whether
the experience of clinical chronic pain varies during the menstrual cycle and,
if so, the hormonal, immunological, neuronal, and psychological correlates of
this variability.

o  Investigate biobehavioral approaches to managing pain associated with acute
and chronic illness such as arthritis, cancer, diabetes, sickle cell disease, low
back pain, headaches, temporomandibular disorders, and other orofacial pain


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 103-43).

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 in the NIH Guide for Grants and Contracts, Vol. 23, No.
11, March 18, 1994 available on the web at the following URL address:


It is the policy of NIH that children (i.e., individuals under the age of 21)
must be included in all human subjects research, conducted or supported by the
NIH, unless there are scientific and ethical reasons not to include them. This
policy applies to all initial (Type 1) applications submitted for receipt dates
after October 1, 1998.

All investigators proposing research involving human subjects should read the
"NIH Policy and Guidelines on the Inclusion of Children as Participants in
Research Involving Human Subjects" that was published in the NIH Guide for Grants
and Contracts, March 6, 1998, and is available at the following URL address:

Investigators also may obtain copies of these policies from the program staff
listed under INQUIRIES. Program staff may also provide additional relevant
information concerning the policy.


Applications are to be submitted on the grant application form PHS 398 (rev.
4/98) and will be accepted at the standard application deadlines indicated in the
application kit. Application 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:

Applicants planning to submit an investigator-initiated new (type 1), competing
continuation (type 2), competing supplement, or any amended/revised version of
the preceding grant application types requesting $500,000 or more in direct costs
for any year are advised that he or she must contact the Institute or Center (IC)
program staff before submitting the application, i.e, as plans for the study are
being developed. Furthermore, the application must obtain agreement from the IC
staff that the IC will accept the application for consideration for award.
Finally, the applicant must identify, in a cover letter sent with the
application, the staff member and Institute or Center who agreed to accept
assignment of the application.  Refer to the NIH Guide for Grants and Contracts,
March 20, 1998 at http://www.nih.gov/grants/guide/notice-files/not98-030.html

Submit a signed, typewritten original of the application, including the
checklist, and five signed photocopies in one package to:

BETHESDA, MD  20892-7710
BETHESDA, MD  20817 (for express/courier service)


Applications will be assigned on the basis of established PHS referral
guidelines.  Applications will be evaluated for scientific and technical merit
by an appropriate scientific review group convened in accordance with the
standard NIH peer review procedures. As part of the initial merit review, all
applications will receive a written critique and undergo a process in which only
those applications deemed to have the highest scientific merit, generally the top
half of 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

The goals of NIH-supported research are to advance our understanding of
biological systems, improve the control of disease, and enhance health. In the
written comments reviewers will be asked to discuss the following aspects of the
application in order to judge the likelihood that the proposed research will have
a substantial impact on the pursuit of these goals. Each of these criteria will
be addressed and considered in assigning the overall score, weighting them as
appropriate for each application. Note that the application does not need to be
strong in all categories to be judged likely to have major scientific impact and
thus deserve a high priority score. For example, an investigator may propose to
carry out important work that by its nature is not innovative but is essential
to move a field forward.

(1) Significance: Does this study address an important problem? If the aims of
the application are achieved, how will scientific knowledge be advanced? What
will be the effect of these studies on the concepts or methods that drive this

(2) Approach: Are the conceptual framework, design, methods, and analyses
adequately developed, well-integrated, and appropriate to the aims of the
project? Does the applicant acknowledge potential problem areas and consider
alternative tactics?

(3) Innovation: Does the project employ novel concepts, approaches or method? Are
the aims original and innovative? Does the project challenge existing paradigms
or develop new methodologies or technologies?

(4) Investigator: Is the investigator appropriately trained and well suited to
carry out this work? Is the work proposed appropriate to the experience level of
the principal investigator and other researchers (if any)?

(5) Environment: Does the scientific environment in which the work will be done
contribute to the probability of success? Do the proposed experiments take
advantage of unique features of the scientific environment or employ useful
collaborative arrangements? Is there evidence of institutional support?

In addition to the above criteria, in accordance with NIH policy, all
applications will also be reviewed with respect to the following:

o The adequacy of plans to include both genders, minorities and their subgroups,
and children as appropriate for the scientific goals of the research. Plans for
the recruitment and retention of subjects will also be evaluated.

o The reasonableness of the proposed budget and duration in relation to the
proposed research.

o The adequacy of the proposed protection for humans, animals or the environment,
to the extent they may be adversely affected by the project proposed in the

The initial review group will also examine the provisions for the protection of
human subjects and the safety of the research environment.

Additional scientific/technical merit criteria specific to the objectives of the
RFA and the mechanism used must be included if they are to be used in the review.


Applications will compete for available funds with all other approved
applications.  The following will be considered in making funding decisions:
Quality of the proposed project as determined by peer review, availability of
funds, and program priority.


Inquiries are encouraged.  The opportunity to clarify any issues or questions
from potential applicants is welcome.

Direct inquiries regarding programmatic issues to:

Dr. Mary Leveck
Division of Extramural Activities
National Institute of Nursing Research
Building 45, Room 3AN-12, MSC 6300
Bethesda, MD  20892-6300
Telephone:  (301) 594-5963
FAX:  (301) 480-8260
Email:  Mary_Leveck@nih.gov

Dr. Patricia Bryant
Division of Extramural Research
National Institute of Dental and Craniofacial Research
Natcher Building, Room 4AN-24E
Bethesda, MD  20892-6402
Telephone:  (301) 594-2095
Email:  BryantP@DE45.nidr.nih.gov

Dr. Judith A. Finkelstein
Neuroscience and Neuropsychology of Aging Program
National Institute on Aging
7201 Wisconsin Avenue, Suite 3C307
Bethesda  MD  20892-9205
Telephone:  (301) 496-9350
FAX:  (301) 496-1494
Email:  jf119k@nih.gov

Dr. James Panagis
Orthopaedics Program Director
National Institute of Arthritis and Musculoskeletal and Skin Diseases
Building 45, Room 5AS-37K
Bethesda, MD  20892-6500
Telephone:  301-594-5055
Email:  panagisj@exchange.nih.gov

Dr. Claudette Varricchio
Community Oncology and Rehabilitation Branch
National Cancer Institute
Executive Plaza North, Suite 300
Bethesda, MD  20892
Telephone:  (301) 496-8541
Email:  varriccc@dcpcepn.nci.nih.gov

Dr. Louis Quatrano
National Center for Medical Rehabilitation Research
National Institute on Child Health and Human Development
Building 61E, Room 2A03
Bethesda, MD  20892-7510
Telephone:  (301) 402-2242
Email:  quatranl@hd01.nichd.nih.gov

Dr. David Thomas
Behavioral Neurobiology Research Branch
National Institute on Drug Abuse
5600 Fishers Lane, Room 10A-19
Rockville, MD  20857
Telephone: 301-443-6975
Email:  dt78k@nih.gov

Dr. Peter G. Kaufmann
Behavioral Medicine Research Group
National Heart, Lung, and Blood Institute
6701 Rockledge Drive MSC 7936
Bethesda, MD  20892-7936
Telephone:  (301) 435-0404
Email:  pvk@cu.nih.gov

Dr. Peter Muehrer
Prevention, Early Intervention, and Epidemiology Research Branch
National Institute of Mental Health
5600 Fishers Lane, Room 18C-14
Rockville, MD  20857
Telephone:  (301) 443-4708
FAX:  (301) 443-4611
Email:  pmuehrer@nih.gov

Dr. Cheryl A. Kitt
Division of Convulsive, Infectious and Immune Disorders
National Institute of Neurological Disorders and Stroke
7550 Wisconsin Avenue, Room 504
Bethesda, MD  20892
Telephone:  (301) 496-1431
FAX:  (301) 402-2060
Email:  kittc@ninds.nih.gov

Dr. Richard L. Nahin
National Center for Complementary and Alternative Medicine
National Institutes of Health
Building 31, Room 5B-36
Bethesda, MD  20892-2182
Telephone:  (301) 496-4792
FAX:  (301) 594-6757
Email:  NahinR@od.nih.gov

Direct inquiries regarding fiscal matters to:

Jeff Carow
Grants Management Officer
National Institute of Nursing Research
Building 45, Room 3AN-12
Bethesda, MD  20892-6301
Telephone:  (301) 594-6869
Email:  jeff_carow@nih.gov

Martin Rubenstein
Division of Extramural Research
National Institute of Dental and Craniofacial Research
Natcher Building, Room 4AS-55
Bethesda, MD  20892-6402
Telephone:  (301) 594-4800
Email:  Rubenstein@DE45.nidr.nih.gov

Joe Ellis
Grants Management Officer
National Institute on Aging
7201 Wisconsin Avenue, Suite 2N212
Bethesda MD  20892-9205
Telephone:  (301) 496-1472
FAX:  (301) 402-3672
Email:  je14j@nih.gov

Sally A. Nichols
Grants Management Officer
National Institute of Arthritis and Musculoskeletal and Skin Diseases
Building 45, Room 5AS-49F
Bethesda, MD  20892-6500
Telephone:  (301) 594-3535
Email:  nicholss@exchange.nih.gov

William T. Wells
Grants Administration Branch
National Cancer Institute
6120 Executive Boulevard, Room 243
Bethesda, MD  20892
Telephone:  (301) 496-7800, ext. 250
FAX:  (301) 496-8601
Email:  William_Wells@nih.gov

Mary Ellen Colvin
Grants Management Specialist
National Institute of Child Health and Human Development
Building 61, Room 8A17G
Bethesda, MD  20892-7510
Telephone:  (301) 496-1303
Email:  colvinm@hd01.nichd.nih.gov

Gary Fleming
Grants Management Branch
National Institute on Drug Abuse
5600 Fishers Lane, Room 8A-54
Rockville, MD  20857
Telephone:  (301) 443-6710
Email:  gfleming@aoada.ssw.dhhs.gov

Marie A. Willett
Grants Management Officer
National Heart, Lung, and Blood Institute
Rockledge Two, Room 7156
Bethesda, MD  20892-7926
Telephone:  (301) 435-0144
Email:  marie_willett@nih.gov

Diana Trunnell
Grants Management Specialist
National Institute of Mental Health
5600 Fishers Lane, Room 7C08
Rockville, MD  20857
Telephone: (301) 443-2805
Fax: (301) 443-6885
Email: diana_trunnell@nih.gov

Karen D. Shields
Grants Management Branch
National Institute of Neurological Disorders and Stroke
Federal Building, Room 1004
Bethesda, MD  20892
Telephone:  (301) 496-9231
Email:  s26n@nih.gov


This program is described in the Catalog of Federal Domestic
Assistance Nos. 93.361, 93.121, 93.866, 93.846, 93.399, 93.865, 93.279, 93.838,
93.242, 93.855, and 93.213.  Awards are made under authorization of the Public
Health Service Act, Title IV, Part A (Public Law 78-410, as amended by Public Law
99-158, 42 USC 241 and 285) and administered under PHS grants policies and
Federal Regulations 42 CFR 52 and 45 CFR Part 74. This program is not subject to
the 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, and 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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