Basic Science Research

Basic Science Research is based on well led controlled experiments which ultimately lead to demonstrated truths.

Basic Science Research Topics

  • Effects of Local Anesthetics
  • AMPA receptor regulation in the brain and spinal cord during chronic neuropathic pain state, or long lasting biochemical changes in the brain and spinal cord that underly chronic neuropathic pain. 
  • The role NMDA Receptors in Chronic Pain following Nerve Injury
  • Investigation of Preclinical Models of Chronic Pain using Electroencephalography (EEG)

Current Basic Science Research Projects

Lisa Doan, MD describes her protocol of looking at local anesthetic effects.
Local anesthetics are often used for spinal and epidural anesthesia, and their use can be associated with postoperative neurological complications such as transient neurological symptoms or cauda equina syndrome. These complications are believed to arise from local anesthetic neurotoxicity (being poisonous to nerves or nerve cells). Previously, the lab studied local anesthetic cytoxicity (toxicity to cells) in human neuroblastoma cells. Six local anesthetics were studied and all were found to be cytotoxic at subclinical doses. Cell death occurred via necrosis (localized death of living cells), though certain local anesthetics through increased concentration or exposure time also triggered apoptosis (programmed cell death). This work is now being extended to a rodent model to further examine the toxicity of local anesthetics. We will investigate the mechanisms of local anesthetic neurotoxicity on the rat spinal cord and the dorsal root ganglia.

Jing Wang, MD, PhD describes his ongoing research of "AMPA receptor regulation in the brain and spinal cord during chronic neuropathic pain state," or "Long lasting biochemical changes in the brain and spinal cord that underlie chronic neuropathic pain." 
Pain is a very complex sensation, but more than a sensation, it also represents a complex behavior. There are many manifestations of pain. There is the sensory component of pain, which represents our nervous system's ability to localize the source of pain and to convey this information from a peripheral site in the body to the brain. There is also an emotional component of pain, which may be characterized as suffering. Finally, there is the executive component of pain, namely, the brain's decision on what should be done about the painful stimulus (to flee, to take analgesics, etc). Through two distinct projects, all these three components of pain are actively investigated. First, we are investigating the role certain brain regions play in processing the emotional and to a lesser degree the executive component of pain. Two limbic regions in the brain – nucleus accumbens and amygdala – are the focus of this inquiry. Nucleus accumbens plays an important role in driving actions in response to a pleasure or reward, but it is also activated by pain. Amygdala, meanwhile, is the emotional center of the brain. Questions being examined include how these two regions are activated by painful stimuli, and once activated, what they do to process the information of suffering. A second project examines the sensory pathway that is necessary for the conduction of neuropathic pain. Neuropathic pain is defined as pain resulting from injury to the somatosensory system, and common examples include phantom limb pain, diabetic neuropathy, HIV neuropathy, etc. Little is known about the activity of the spinal cord neurons in the absence of nervous information, which is what occurs in deafferentation pain such as phantom limb pain. A hypothesis that is being tested is that in the presence of a nerve injury, prolonged lack of sensory input as the result of deafferentation may actually increase the activity in the spinal cord neurons, resulting in the erroneous conduction of the painful signal.

Esperanza Recio-Pinto, PhD and Thomas J.J. Blanck, MD, PhD describe their research, "The role NMDA Receptors in Chronic Pain following Nerve Injury"
The role of NMDA receptors (NMDArs) in pain sensation was initially uncovered in 1987 when the hyper-excitability of spinal cord dorsal horn nociceptive neurons evoked by C-fiber stimulation was found to be blocked by spinal delivery of NMDAr antagonist (Davies & Lodge 1987; Dickenson & Sullivan 1987). Since then many studies have focused on the role of central NMDArs in pain sensation. It is now apparent that peripheral NMDArs also play a role not only in the initiation but also in the maintenance of chronic pain states particularly those following peripheral nerve injuries. Such studies have mostly concentrated in the changes of central terminals of dorsal root ganglia (DRG) neurons that may contact with the spinal dorsal horn sensory neurons. In patients, the development of chronic pain following surgery has been shown to correlate with the presence of peripheral nerve injury (Macrae 2001). Peripheral NMDArs are an attractive target for treating chronic pain involving surgical procedures, because under normal (non-painful) stimulation NMDArs in dorsal root ganglia (DRG) neurons do not activate, some of the NMDArs isoforms are predominantly expressed in DRG neurons, and NMDArs have various regulatory sites that are isoform-dependent and hence one could select treatments directed solely at peripheral NMDAr and in this way avoid unwanted CNS side effects. Of particular interest is the role of NMDArs not only on peripheral DRG neurons but also on their surrounding satellite glial cells, since neuronal-glial interactions have been shown to contribute to injury-evoked neuronal hyperexcitability. In addition, the identification of paths that are under the control of peripheral NMDAr and that contribute to the maintenance of chronic pain states will help select treatments that will not only decrease but potentially also reverse the chronic pain states observed following peripheral nerve injury. We are using in vivo and in vitro studies in order to indentify nerve injury-evoked changes that involve peripheral NMDAr activity that could contribute to the initiation and/or maintenance of chronic pain. We are using the spared tibial and sural nerve injury models (two of the sciatic nerve branches) in order to identify which of the nerve injury-evoked changes in the expression and function of NMDAr in both injured and “uninjured” fibers within the sciatic nerve, contribute to the initiation and maintenance of mechanical allodynia. Since both DRG neuronal soma and their surrounding satellite glial cells contain substance P. We are also interested in studying how substance P through actions on the soma of DRG neurons (in particular on paths activated by NMDAr) could contribute to the enhancement of peripheral neuronal excitability.

Kevin Gingrich, MD, ME describes his research, "Investigation of Preclinical Models of Chronic Pain using Electroencephalography (EEG)"
Unrelenting pain can lead to a condition of chronic pain which is thought to involve pathological alterations in the way the brain perceives pain. Chronic pain is poorly understood, difficult to treat, and affects more than 10% of the US population. Emerging evidence suggests that chronic pain is associated with human brain dysfunction that can be detected by measuring brain electrical activity using EEG and MEG (magnetoencephalography). Advances in understanding human disease and the subsequent development of effective treatments can be markedly accelerated by the development of preclinical models that parallel human pathophysiology. As a first step in pursuit of this goal, the Division of Pain Medicine (Anesthesiology) in collaboration with the Department of Neurosciences at NYU are currently investigating changes in brain function in rodent pain models using EEG.