Optogenetics and photopharmacology in pain researchand therapeutics

Abstract

Pain afflicts billions of people worldwide, who suffer especially from long-term chronic pain. This gruelling condition affects the nervous system at all levels: from the brain to the spinal cord, the Dorsal Root Ganglia and the peripheral fibres innervating the skin. The nature of the different molecular and cellular components of the somatosensory modalities, as well as the complexity of the peripheral and central circuitry are yet poorly understood. Light-based techniques such as optogenetics, in concert with the recent advances in single-cell genetic profiling, can help to elucidate the role of diverse neuronal subpopulations in the encoding of different sensory and painful stimuli by switching these neurons on and off via optically active proteins, namely opsins. Recently, photopharmacology has emerged from the efforts made to advance optogenetics. The introduction of azo-benzene-based light-sensitive molecular switches has been applied to a plethora of molecular targets, from ion channels and receptors to transporters,enzymes and many more, some of which are paramount for pain research and therapy.In this review, we summarise the past and ongoing research in the fields of optogenetics and photopharmacology and we discuss the use of light-based techniques for the investigation of acute and chronic pain physiology, besides their potential for future therapeutic use to improve pain treatment.