George Berkeley theorized that reality is a product of the mind, arguing that, "... sensible things are only to be perceived by sense or represented by the imagination" \[[@R1]\]. Berkeley's idealism---*esse est percipi aut percipere*, or, to be is to be perceived or to perceive---though lacking peer-reviewed, reproducible experimentation, withstands many objections: what can we perceive beyond that which we sense? Of course, immaterialism is irrelevant to the practical workings of our daily lives and it precludes the study of the myriad, complex ways in which our minds manifest across different time and length scales to fashion ideas, perceptions, and senses into reality. In this *Yale Journal of Biology and Medicine* (YJBM) focus issue on Sensory Biology and Pain, we bring you a more nuanced view of the mind and of the workings of senses and pain. 

Sensory biology and pain begins with inputs---light, smell, taste, touch, sound, balance, in the case of sensory biology, or at points proximal to synapses in our bodies, in pain. These inputs are signals, detected by various receptors, that are parsed and interpreted by the nervous system. These labyrinthine, exquisite, and multi-scale neural structures and systems, which constitute our minds, were beautifully illustrated by the neuroscientist, Santiago Ramón y Cajal, whose portrayals serve as the inspiration for this issue's cover art. 

Along with topics in the biology of sensory perception, in this issue, we consider the specialized sensory neurons, nociceptors, which relay the bodily representation of pain to the nervous system. Today, the difficulty in understanding and managing patients' pain has led to widespread problems in the overuse of---and addiction to---opioid medications. In 2017, the US Department of Health and Human Services (HHS) declared that the opioid epidemic was a public health emergency. Upon this declaration, the HHS suggested a 5-point strategy to combat the opioid crisis. Two of these strategic points called for enhanced understanding of the epidemic and broadened support for innovative research. In this issue, we interviewed a public health official and active researcher, Dr. Bertha Madras, who is currently a member of the President's Commission on Combating Drug Addiction and the Opioid Crisis and the former Deputy Director for Demand Reduction in the White House Office of National Drug Control Policy (Ogawa). Madras walks us through how the "opioid commission's" report was created, what its principal recommendations are, and what is forthcoming, in terms of prevention and research. We share deeper insights and updates about research into pain and addiction medicine with interviews of Dr. Stephen Waxman, whose research focuses on pain treatment, especially in treating pain that arises from the dysfunction of the nervous system, and Dr. Patrick O'Connor, one of the founders of the new Program in Addiction Medicine at Yale University's School of Medicine; pertinently, O'Connor's research lies at the crossroads of public health policy, primary care, and addiction (DeNardo and Horien, respectively). 

Apart from the opioid crisis, we also cover other topics in pain and clinical research, including a mini-review on the history and treatment of the main cause of non-traumatic cervical spinal cord (neck) injury in adults, degenerative cervical myelopathy (DCM) (Gibson *et al*.). Gibson *et al*. review the history of DCM, its symptoms, the physiological progression of chronic spinal cord compression, its diagnosis by imaging, and the outcome of surgical treatment. On the topic of clinical pain management, we also offer an original research article on emergency medicine best practices for patients admitted to the emergency room expressing sudden-onset, severe pain and headaches (Gill *et al*.). 

On the topic of sensory biology, Borges offers a review on how the organisms involved in nocturnal pollination have evolved sensory systems for low-light environments. Borges focuses on adaptations in the visual system for nocturnal pollinators, reviewing adaptations across the pollinators' eye, photoreceptors, and central nervous system, all of which work together to increase organisms' sensitivity to environmental cues. Nocturnal pollinators face less competition than their diurnal pollinators, which, Borges suggests, may explain why entire groups, such as bats, are nocturnal. 

Continuing with the theme of visual systems, albeit in humans, Yang *et al*. review the cornea, which, apart from maintaining structural integrity and sensation in our eyes, is also one of our most densely innervated tissues. Yang *et al*. review corneal disease and treatment and suggest that corneal disease, whose diagnosis relies on non-invasive, *in vivo*confocal microscopy, and can sometimes be treated with non-invasive laser refractive surgery, offers a glimpse into potential diagnoses and treatments of other densely innervated tissues, beyond the cornea, without the risk of invasive diagnoses or treatments. 

Offering a molecular and biochemical viewpoint of the visual system, Detwiler provides a mini-review of the molecular mechanisms of visual receptors in the eye, concentrating on a light-sensitive G-protein coupled receptor, melanopsin, that is expressed in a class of photoreceptors in the eye, called ganglion cells. Many aspects of the light transduction process in ganglion cells are either debated or unknown. Detwiler discusses these outstanding challenges in studying light transduction in photosensitive ganglion cells and hints that differences between cell types and organisms within the ganglion cell class may offer clues about these cells' salient functional mechanisms. 

Switching focus to the olfactory system, Gaudry reviews the elusive role of serotonin and its influence on mice and fruit fly olfactory processing. Gaudry specifically focuses on the role that serotonin has on the modifying olfactory circuits as olfactory learning and development is taking place. Gaudry's approach is to compare how serotonin modulates olfactory processes between species and to use their similarities and differences to extract general principles. Gaudry pushes us to consider that the serotonin-sensitive receptor, 5-HT, may have multiple effects on olfactory processing, a prospect which remains an open question. 

Moving away from animal models and into the city, consider this: if you step into any urban environment and try to focus on what your senses are telling you, undoubtedly you'll notice a cacophony of sirens and other commotions, a plethora of complex smells and pollutants, and an oppression of resplendent light. In this issue, Hoover provides us with several examples of how these novel human-environment interactions outpace evolution and lead to sensory-impairment. Hoover concentrates on olfactory loss and the intersection of a protuberance of pollution with an unequal distribution of environmental justice along socioeconomic lines. Hoover reminds us that these sensory impairments often adversely affect under-privileged individuals in a society and suggests policy and research interventions to combat this inequity.

After reading this issue, you will be reassured that the complexity of sensory biology and pain reflects the multiplicities of reality itself; perhaps you will even move forward with a deeper intricacy, appreciation, and understanding of our mind than Bishop Berkeley offered. Yet, as we learn from experts in pain and addiction medicine, there are many pressing issues to resolve. As Dr. Madras reminds us, pain is a difficult phenomenon to understand because there are different types, origins, manifestations, perceptions, and methods to diagnose, treat, and manage pain (Ogawa). As Dr. O'Connor and Dr. Waxman point out, there are still many questions, regarding pain receptors, that need to be studied before we can understand how and why pain arises at the molecular level (Horien and DeNardo, respectively). So, we hope that this is neither a last inquiry for YJBM nor for you but, rather, a continuation of the exploration into the biology that so wonderfully evolved to enable such sensory-deprived and functionally successful behaviors as nocturnal pollination (Borges) and whose impairment extensively impacts our way of life, our society, and our culture (Hoover).

HHS

:   Department of Health and Human Services

DCM

:   degenerative cervical myelopathy
