Pain Research

Considerable advances have been made in the past 10 years with regard to our understanding of the mechanisms underlying nociception. These advances have led to tangible developments in human pain therapy. There remains, however, a significant gap between the basic research and the implementation of new approaches. There is an evolving appreciation that a variety of underlying mechanisms may be in play that account for the difficulty faced by the clinician in managing that pain. Moreover, there is considerable fruitful work being undertaken with respect to the mechanisms of nociception. It is clear that pain states are themselves uniquely complex and the pharmacology, physiology and molecular biology associated with the mechanisms underlying pain reflect issues that are of fundamental interest to neurobiologists. It is thus our aim to bring current research approaches to bear on the mechanisms underlying chronic pain states. It is our belief that such approaches represent important basic scientific issues, but of particular importance, they are essential for developing efficacious methods for managing pain syndromes.

Members of the pain research program

The membership of the pain research program reflects individuals with considerable focus in the area of pain research. All are members of the Department of Anesthesiology. This group may be characterized in terms of a high level of funding, a consistent record of publication and a high level of interaction and collaboration.

Members of the Clinical Pain Research Program include:

Tobias Moeller-Bertram, M.D., Program Director
Peggy Mollen, R.N., CCRC, Associate Director (pmollen@ucsd.edu)
Sandra Woods, RN Clinical Nurse II
Vicky Lam, B.S. Staff Research Associate III
Cindy Martin, LVN, Staff Research Associate III
Tahir Syed, Staff Research Associate II

Preclinical Research

Facilities

There are two sites. The CTF laboratory is a secured and alarmed facility, approximately 4100 sq. ft., and is located on a single floor of the Clinical Teaching Facility at the University of California, San Diego (UCSD) Medical Center. The second site is an 1800sq ft space in the Medical Teaching Facility on the La Jolla campus. Each of the preclinical investigators has independent laboratory space, but the group is organized into a series of research cores to optimize interaction and cost sharing. All shared facilities operate on a recharge basis so that the direct expense is born by each user.

Preclinical Research Goals

The following outlines the essential targets encompassing the preclinical mission statement of the pain program.

1. Mechanisms of nociception that arise from disease and from therapy.

Effect on nerve function effects of radiation and chemotherapeutic agents that lead to nerve damage (central and peripheral) that yields neuropathic pain states.
- Assessment of allodynia, hyperalgesia
Treatment effect / tumor upon nerve / DRG / spinal cord
- Local tumor / Intrathecal tumor
- Radiation
- Chemotherapeutic agent: Systemic/intrathecal
Release of central and peripheral transmitters
Sprouting of central and peripheral terminals
Change in sympathetic innervation of DRG and radiated site (skin / muscle dura).
- Time course
- Effect of suppressed/ altered immunogenicity
Effect of tumor / type on nerve function (spontaneous activity)
Changes in central indices
- Regulation of central receptors (NK1 up/down regulation) / IEG expression

2. Implementation of mechanistic insights into the evolution of animal models of nociceptive processing (hyperalgesia, allodynia, spontaneous pain states) after tumor, radiation, chemotherapy and/or various combinations.

Definition of hyperalgesia allodynia-hyperalgesia / pain thresholds
Parallel time course with changes in nerve morphology and central changes

3. Implementation of animal models to develop mechanistic screening approaches that will target directions of pain therapy

Spinal pharmacology of induced hyperalgesic and neuropathic states
Anti-cytokines, growth factors

4. Use of preclinical models in defining evolution of tolerance/dependence

Effects of radiation and chemotherapy on analgesic tolerance

Clinical Research Program

A strong clinical management program provides the basic foundation for a clinical research program. The clinical component of the pain research program is unique in that it feeds off of the intense preclinical program that has and will continue to be developed. This has allowed organization of clinical research protocols based on good science. Dr. Wallace and Dr. Yaksh have developed a strong clinical research program strongly linked to the preclinical work. The program has the following components.

1. Pharmacology of Human Experimental Pain

Several specific mechanisms have been proposed for encoding nociception. We have implemented human models that are believed to reflect these mechanisms and can employ them in normal human volunteers. These models involve both experimental pain states in human volunteers and neuropathic pain states. Examples of cancer pain syndromes that we believe are fitted by these models include postmastectomy pain, postherpetic neuralgia, radiation-induced neuritis, chemotherapy induced peripheral neuropathy, and tumor invasion of peripheral nerves.

2. Alternative Therapies for Pain

Currently, patients spend billions of dollars per year on alternative health care in spite of lack of solid scientific support. NIH has initiated a section on integrative medicine that signals the importance of this aspect of medicine. We currently have research protocols in place looking at the effects of acupuncture on pain and symptom management.

3. Preclinical Directed Research

Much of the work of the preclinical group feeds information into the clinical research program. Information gathered from this preclinical work is used to develop clinical research protocols. These involve the use of existing drugs and lead to the development of new drugs that require an IND and phase I studies.

4. Clinical Trials in Pain

There are many new analgesics emerging in the market. Pharmaceutical companies are looking for reliable sites to study these new drugs. We have developed a service that is user friendly to these companies. Our service currently has a good track record with phase I-IV clinical trials. We have been very successful with patient enrollment but can always do better. For information of currently active clinical trials, please contact Peggy Mollen, R.N., at pmollen@ucsd.edu or (858) 657-7099.