Molecular and Cellular Neuroscience Program
Center for Integrative Craniofacial Research
OBJECTIVE: The objective of this Initiative is to stimulate research to develop and utilize novel animal models of chronic orofacial pain conditions that provide insight into the biological mechanisms underlying these disorders. A second objective is to stimulate research on patients with chronic painful disorders that will also aid in the understanding of pain and analgesic mechanisms. As an adjunct to the first two objectives, this Initiative will encourage the development of similar measures of pain in patients and animals that are non-invasive and objective, and that permit a behavioral or functional assessment of pain.
This Initiative will stimulate research approaches that are of increasing importance for pain research and that focus on mechanisms of disease. The primary outcome of this Initiative will be 1) an increased knowledge of pathophysiological mechanisms underlying chronic orofacial pain disorders, and 2) an increased knowledge of biological mechanisms underlying nociception. An additional outcome may be a better understanding of approaches and behaviors in healthy people that will diminish the likelihood of developing chronic painful conditions. Results from this Initiative will provide a basis for translating newly discovered mechanistic data into better therapeutic approaches for chronic pain disorders.
BACKGROUND: Approximately 10% of Americans suffer from chronic pain conditions. A significant portion of these patients have chronic orofacial pain. Orofacial pain disorders encompass a wide range of conditions including temporomandibular joint disorders, periodontal pain, trigeminal neuralgia, atypical face pain, burning mouth syndrome, dental surgical pain, head and neck cancer pain, pain due to oral infections, and other neuropathic and inflammatory pain conditions. The current treatments for chronic pain are less than satisfactory and there is a lack of new approaches to treat these conditions. Inability to effectively treat acute pain may result in progression to chronic pain conditions and a spiral of disability, depression, and further utilization of medical resources. Chronic pain disorders cost the U.S. approximately 80 billion dollars a year in health care costs and lost productivity.
Undertaking clinical studies early on in the analgesic development process will better inform and direct the discovery of new, efficacious therapeutics. Current human studies and measures of acute and chronic pain may not be entirely representative of clinical pain conditions. Stimulus-induced measures of nociceptive behavior (i.e. thermal and mechanical sensitivity) are routinely used in basic studies to assess acute and chronic pain and they reliably measure the sensory aspects of pain. In a clinical setting however, pain measures usually rely on self-reporting, may be activity-dependent, and necessarily include psychosocial influences. In addition, clinical pain reported by patients may be spontaneous or continuous as well as stimulus-induced like that measured in animal studies.
Clinical orofacial pain studies in humans may involve measurement of the effectiveness of analgesic drug treatments in reducing pain after dental extraction or other noxious treatment; another approach measures the latency to respond to a noxious thermal or mechanical stimulus. This latter approach typically involves cutaneous or muscular injections of various irritants. It is not clear if these types of experiments are reflective of human clinical pain states since, in these studies the pain disappears with a predictable time course. Some animal models of orofacial pain that have been used include infraorbital nerve ligation or axotomy; injection of inflammatory agents into the vibrissal pads, temporomandibular joint, or masseter muscle; and intradental or dural application of irritants. These examples have served as models for neuropathic and inflammatory facial pain, temporomandibular joint disorders, dental pain, and migraine headache. It is now appropriate to look beyond these models and to develop truly novel approaches that will lead to a better understanding of human pain and analgesic mechanisms.
Successes in treating experimental pain in animal studies in the laboratory have rarely been followed by successful therapeutic outcomes in clinical trials of chronic pain conditions. There are many reasons for this failure. Most importantly, we do not fully understand the pathophysiological mechanisms underlying the development and persistence of chronic pain disorders. Consequently, we have not been able to identify appropriate new targets and pathways critically involved in these disorders. Second, current animal models and measures of chronic pain probably do not reflect human chronic pain disorders. Thus, we lack animal models and appropriate dependent measures of chronic pain that reliably identify therapeutic targets useful in treating human chronic pain. Much of current pain literature focuses on peripheral pain and spinal nerves and the information gathered from these studies is relevant to trigeminal mechanisms. However, fewer studies have explored chronic pain mechanisms in animal models specifically relevant to the trigeminal system. This Initiative aims to stimulate this area of research by focusing on science that will utilize new animal models of pain and studies of humans with chronic pain disorders in order to discover pathophysiological mechanisms underlying the development and maintenance of chronic pain states.
Current Portfolio Overview: The current NIH portfolio of grants broadly related to pain research totals approximately 1,000 and the NIDCR portfolio totals about 60. While the NIDCR portfolio contains grants that address mechanisms of nociception and pain perception, few utilize behavioral animal models and few utilize studies of humans with chronic pain conditions. Thus this Initiative will attempt to fill those gaps and provide research results that will better characterize the biological mechanisms underlying chronic pain conditions.
Collaborative Activities: The objectives and content of this Concept Clearance are consistent with the interests of the Institutes and Centers participating in the NIH Pain Consortium and the NIH Blueprint for Neuroscience.