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." 
Our research interest is centered on the role of brain circuits in the regulation of acute and chronic pain. One of our projects aims to understand how glutamatergic projections from the prefrontal cortex to the nucleus accumbens - an important projection in the brain for reward-based learning - can modulate acute and persistent postoperative pain in rodent models. We have shown over the last three years that this projection relieves both sensory and affective components of pain. A translational extension of this project is pre-clinical and clinical investigations of pharmacological agents that alter glutamate signaling such as ketamine or AMPA receptor potentiators in postoperative pain management. A second project in our laboratory aims to use computational methods to decode acute pain in the brain. We are successful in decoding both the onset and intensity of pain in rodents using supervised and unsupervised machine learning algorithms. The eventual goal for this project is the development of a brain-computer interface approach to neuromodulation so as to decode and treat pain in real time in patients. Meanwhile, we are also conducting clinical studies on postoperative and chronic pain. Specifically, we have ongoing clinical trials to examine the role of ketamine in postoperative pain control, we are taking a big data approach to investigate risk factors for postoperative pain, and finally, we are using PET/MRI to look at the brain of chronic pain patients before and after epidural steroid injections.

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.