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ARRA Investments in Pain

Public Health Burden
Pain is one of the most costly and pervasive public health problems facing the United States. According to the Centers for Disease Control and Prevention, chronic pain is the leading cause of disability in the United States. Chronic pain can have a tremendous impact on quality of life, affecting peoples’ physical and mental health, employment prospects, job performance, and family and social relationships.

Understanding Pain Pathways
The conscious perception of pain is the result of the activation of pain-sensing neurons called nociceptors, transmission of pain signals to the brain and subsequent processing of the signals. These events require the coordinated participation of a variety of molecules, chemical pathways, and neural circuits, and the process is poorly understood. ARRA-funded projects are supporting the following projects:
  • An ARRA-funded study is investigating how circuitry within the spinal cord permits the mixing of sensations, causing the brain to misinterpret light touch as pain. This study will help researchers understand why the pain pathway is normally suppressed during light touch, and provide important information on how to control pain.1
  • A supplement will advance research on a project investigating how the Mas-related genes, a recently-discovered gene family that is expressed specifically in neurons involved in pain transmission, function in the regulation of pain.2
  • Researchers received an ARRA-supplement to a grant investigating how pain signals reach the brain, and how sensitization of this pathway leads to persistent pain states. This project will use behavioral, electrophysiological, and functional magnetic resonance imaging (fMRI), to understand why and how people experience pain.3
Mechanisms of Chronic Pain in Disease
Chronic pain, pain that lasts for an abnormally long period of time after an injury or disease process, is associated with many conditions, such as arthritis, cancer, fibromyalgia, diabetes, and headache and migraine. Several ARRA-funded studies are investigating the causes of chronic pain:
  • One study is exploring how the function of proteins in spinal cord neurons that are involved in pain transmission is altered in type II diabetes. This study will investigate why these molecules fail to regulate pain in diabetic neuropathy.4
  • ARRA funds are supplementing an ongoing project to investigate how different genes involved in the function of calcium channels affect pain-sensing spinal nerves. This study proposes that an alteration in calcium channels following nerve injury can contribute to neuropathic pain, or feelings of cold, burning, “pins and needles” sensations, and numbness.5
  • Researchers are studying sex- specific regulation of a certain gene by estrogen, which may contribute to increased vulnerability of women to symptoms of chronic pain.6
  • Projects are underway to study how migraine, a neurological condition characterized by severe painful headaches, develops. ARRA funds are supplementing research on triptans, antimigraine drugs that relieve migraine pain, to better understand the basic mechanisms of migraine7.  Another project is studying pain-facilitating neurons before and after inflammation in order to understand the pain associated with migraine headaches.8
Treatment for Chronic Pain
Although some treatments are currently available, chronic pain remains very difficult to treat. The identification of new therapies to attenuate pain, as well as understanding individual differences in response to therapeutics, is a high priority. ARRA-funded projects in this area are addressing the following:
  • Researchers are using newly discovered, naturally occurring toxins derived from the venom of Australian funnel-web spiders to develop drugs that interfere with molecules that conduct pain signals.9
  • A Challenge Grant is exploring a drug that may “reset” chronically activated cells that maintain pain states, thus returning their activity to normal levels and alleviating chronic pain.10
  • Researchers are developing artificial nerves to repair injured nerves by focusing on the arrangement of Schwann cells, cells that surround and protect nerves. These artificial nerves may replace injured nerves that contribute to the sensation of pain.11
  • ARRA funds are supplementing a grant on how the loss of a certain class of neurons that inhibit pain contributes to enhanced and prolonged pain. This study will explore how stem cell transplantation could restore mechanisms in the spinal cord that inhibit pain signaling, and therefore alleviate pain.12
  • ARRA funds are supporting a supplement to an ongoing project that uses a common clinical pain model to identify and characterize psychosocial, physiological and genetic factors that contribute to ethnic group differences in pain perception.13

  1. 2R01NS029797-15 -- Inhibition separating touch and pain- MacDermott, Amy B. (NY)
  2. 3P01NS048499-05S1 -- Role of the Mrg family of GPCRs in nociception Anderson, David J (CA)
  3. 3R01NS039426-09S1 -- Supraspinal Processing of Sensory Aspects of Pain- Coghill, Robert C. (NC)
  4. 2R01NS045602-06A2 -- Mechanisms of Spinal Plasticity in Diabetic Neuropathic Pain Pan, Hui-lin (TX)
  5. 3R01NS055251-04S1 -- N-type Calcium Channels in Nociceptive Neurons- Lipscombe, Diane (RI)
  6. 1R21NS066307-01 -- Sex-specific gene regulation of neuronal chloride co-transporter, kcc2- Liedkte, Wolfgang B. (NC)
  7. 3K08NS047113-05S1 - Mechanisms of Triptan Action in Migraine and Pain- Ahn, Andrew H. (CA)
  8. 1R01NS065406-01 Migraine headache and central pain facilitating systems- Heinricher, Mary M. (OR)
  9. 1R21NS058330-01A2 -- Novel Analgesics from Australian Funnel-Web Spider Venom- Nitabach, Michael Nathan (CT)
  10. 1RC1NS067807-01 -- Spinal adenosine modulator: enduring anti-inflammatory action in neuropathic pain- Watkins, Linda (CO)
  11. 1R21NS063084-01A1 -- Transplantation of Autologous Schwann Cells for the Repair of Segmental Periphera- Levi, Allan D. (FL)
  12. 3R01NS051667-04S1 -- Neural Transplants and Spinal Neuropathic Pain Processes- Sagen, Jacqueline (FL)
  13. 3K01NS055094-04S1 -- Ethnic Differences in Acute Pain and Analgesic Response- Hastie, Barbara A (FL)

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