Colon afferents: molecular identity, histology/morphology and hypersensitivity

Irritable bowel syndrome (IBS) is estimated to affect up to 15% of the population in the USA with chronic visceral pain as its cardinal symptom. Accumulating evidence suggests that heightened peripheral sensory input from colorectal afferents (i.e., afferent sensitization) is necessary for the persistence of IBS-related pain. The goal of this research is to investigate molecular/neurochemical identities and histological locations of functionally distinct afferent classes in the colorectum, from which information about mechanisms of afferent sensitization that contribute to colorectal hypersensitivity will be revealed by complementary computational simulation of afferent neural encoding.



Mechanisms of DRG stimulation to modulate visceral afferent function

Dorsal root ganglia (DRG) have recently emerged as a promising neuromodulatory target to manage certain types of chronic pain according a pilot clinical study. But it remains unknown whether and in what mechanisms visceral pain could be effectively attenuated by DRG stimulation. Since sensitization of visceral afferents is necessary for the persistence of visceral pain, we focus here on elucidating the underlying mechanisms to attenuate or reverse visceral afferent sensitization (and thus treat visceral pain) via DRG stimulation. To achieve that, we are currently developing a multichannel microelectrode array through MEMS technology and working on its application in a novel ex vivo preparation that includes colon/rectum, DRG and dorsal rootlets in continuity for simultaneous single-unit recordings of visceral afferents.



Biomechanics of colorectal tissue and the micromechanical environment of the sensory afferent endings

Afferent terminal complex is responsible for transducing stimuli (typically mechanical) into a generator potential, and encoding the generator potential into action potential spikes, the understanding of which requires two seemly distinct areas of knowledge: afferent neuron physiology and biomechanics of colorectal tissue. This heavily understudied area will be pursued by 1) mechanical tests to determine the bulk mechanical properties of the distal colon and rectum, 2) morphological analyses of afferent nerve endings in the colon and rectum by combining ex vivo single-unit recordings with nerve tracing of colorectal afferents, and 3) a mechanical finite element analysis to investigate the local mechanical stress and strain at the nerve ending – colorectal tissue interface.