title: Probing pain pathways with light.
abstract: We have witnessed an accelerated growth of photonics technologies in recent years to enable not only monitoring the activity of specific neurons, while animals are performing certain types of behavior, but also testing whether specific cells, circuits, and regions are sufficient or necessary for initiating, maintaining, or altering this or that behavior. Compared to other sensory systems, however, such as the visual or olfactory system, photonics applications in pain research are only beginning to emerge. One reason pain studies have lagged behind is that many of the techniques originally developed cannot be directly implemented to study key relay sites within pain pathways, such as the skin, dorsal root ganglia, spinal cord, and brainstem. This is due, in part, to difficulties in accessing these structures with light. Here we review a number of recent advances in design and delivery of light-sensitive molecular probes (sensors and actuators) into pain relay circuits to help decipher their structural and functional organization. We then discuss several challenges that have hampered hardware access to specific structures including light scattering, tissue movement and geometries. We review a number of strategies to circumvent these challenges, by delivering light into, and collecting it from the different key sites to unravel how nociceptive signals are encoded at each level of the neuraxis. We conclude with an outlook on novel imaging modalities for label-free chemical detection and opportunities for multimodal interrogation in vivo. While many challenges remain, these advances offer unprecedented opportunities to bridge cellular approaches with context-relevant behavioral testing, an essential step toward improving translation of basic research findings into clinical applications.
authors.affiliation: Institut universitaire en santé mentale de Québec, Université Laval, Québec, QC, Canada.
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.affiliation: Institut universitaire en santé mentale de Québec, Université Laval, Québec, QC, Canada; Centre d'optique, photonique et laser, Université Laval, Québec, QC, Canada.
authors.forename: Erik
authors.initials: E
authors.lastname: Bélanger
authors.affiliation: Institut universitaire en santé mentale de Québec, Université Laval, Québec, QC, Canada; Département de biochimie, microbiologie et bioinformatique, Université Laval, Québec, QC, Canada.
authors.forename: Marie-Eve
authors.initials: ME
authors.lastname: Paquet
authors.affiliation: Institut universitaire en santé mentale de Québec, Université Laval, Québec, QC, Canada; Centre d'optique, photonique et laser, Université Laval, Québec, QC, Canada; Département de physique, de génie physique et d'optique, Université Laval, Québec, QC, Canada.
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Côté
authors.affiliation: Institut universitaire en santé mentale de Québec, Université Laval, Québec, QC, Canada; Centre d'optique, photonique et laser, Université Laval, Québec, QC, Canada; Département de psychiatrie et neurosciences, Université Laval, Québec, QC, Canada. Electronic address: yves.dekoninck@neuro.ulaval.ca.
authors.forename: Yves
authors.initials: Y
authors.lastname: De Koninck
mesh_terms: D000818:Animals; D006801:Humans; D009434:Neural Pathways / Q000000981:diagnostic imaging / Q000503:physiopathology; D061848:Optical Imaging / Q000295:instrumentation / Q000379:methods; D062308:Optogenetics / Q000295:instrumentation / Q000379:methods; D010146:Pain / Q000000981:diagnostic imaging / Q000503:physiopathology*
keywords: fiber-optics; nociceptive processing; nonlinear microscopy; optogenetics; optrodes