Neurobiology of stress and visceral pain
My research program is pursuing translational studies in the areas of neurobiology of visceral pain and stress. This program is supported by a recently awarded NIH Center grant as well as by RO1s of the senior investigators.
On a cellular and molecular level, we are studying mechanisms underlying the transduction and neuroplasticity of primary and secondary afferent neurons in response to noxious visceral stimulation, using electrophysiologic, immunocytochemical and molecular techniques. A primary focus of research in this area is the identification and characterization of receptors and signaling mechanisms on peripheral terminals of DRG neurons such as VR1, CB1R, NMDA and PAR receptors. In addition, plasticity of synaptic transmission between primary and secondary afferents are studied in spinal cord slices. The longterm goal of these studies is the characterization of mechanisms underlying the development of chronic visceral hyperalgesia and the development of effective viscero-analgesic drugs.
On an animal experimental level, we are characterizing alterations in stress-induced pain modulation, in behavioral responses and in HPA axis responses in rats which have been exposed to neonatal stress. Behavioral changes are related to permanent neuroplastic changes in the CNS of neonatally stressed animals. These studies focus on the role of altered central CRF release and changes in stress-induced opioid analgesia. Long term goal of these studies is to develop an animal model with high face and construct validity for stress-related disorders.
On a human level, we are characterizing neuroendocrine, autonomic and perceptual responses to various stressors in healthy control subjects and patient population with chronic stress disorders, such as functional gastrointestinal disorders and fibromyalgia. In collaborative studies with the UCLA Brain Mapping Division, we study central representations of visceral stimuli, including pain, in normal volunteers and patients with chronic abdominal pain syndromes, using functional brain imaging techniques such as positron emission tomography (PET) functional MRI and ERP. We are evaluating the effect of emotions and acute stressors on these visceral pain responses. The longterm goal of these studies is to identify cerebral alterations underlying abnormal perceptual, neuroendocrine and autonomic responses to visceral pain at the receptor level, and to evaluate pharmaceutical compounds with selective effects on visceral pain.