This book is being published at a time when opioid receptors have recently been cloned. The structural characteristics of opioid receptors and the recent advances in their molecular cloning and expression are explicated. Connecting these cloned opioid receptors with the pharmacology of opioid receptor actions is of particular importance. The use of antisense oligodeoxynucleotides to opioid receptors to elucidate the neural mechanisms of opioid action is detailed. As analgesia is one of the most important clinical functions for opioids and opioid peptides, this book concentrates on the detailed mechanisms of action of opioids and opioid peptides for the production of analgesia. The significant pharmacologic actions of opioids and opioid peptides in gastrointestinal function, immune function, cardiovascular and respiratory regulation, addiction and the cellular mechanisms involved in tolerance and dependence of opioids are also described. The book will be of interest both to researchers investigating the neural mechanisms of the pharmacologic and physiologic functions of the endogenous opioid system and to clinicians who are involved in pain management and assessment.

Advances in itch research have elucidated differences between itch and pain but have also blurred the distinction between them. There is a long debate about how somatic sensations including touch, pain, itch, and temperature sensitivity are encoded by the nervous system. Research suggests that each sensory modality is processed along a fixed, direct-line communication system from the skin to the brain. Itch: Mechanisms and Treatment presents a timely update on all aspects of itch research and the clinical treatment of itch that accompanies many dermatological conditions including psoriasis, neuropathic itch, cutaneous t-cells lymphomas, and systemic diseases such as kidney and liver disease and cancer. Composed of contributions from distinguished researchers around the world, the book explores topics such as: Neuropathic itch Peripheral neuronal mechanism of itch The role of PAR-2 in neuroimmune communication and itch Mrgprs as itch receptors The role of interleukin-31 and oncostatin M in itch and neuroimmune communication Spinal coding of itch and pain Spinal microcircuits and the regulation of itch Examining new findings on cellular and molecular mechanisms, the book is a compendium of the most current research on itch, its prevalence in society, and the problems associated with treatment.

Opioid peptides have long been known to have regulatory effects on sexual behavior. Endogenous opioids affect reproductive function in both men and women, and the effects of exogenous opioid use are often described in sexual terms as an "orgasmiclike" euphoria. Moreover, long-term opioid use results in a deterioration of sexual function. Studies have shown similar regulatory effects on sexual behavior in rodent models, in which opioids facilitate sexual motivation and inhibit sexual performance. Of the three opioid receptors (mu, delta, and kappa), anatomical, gene manipulation, and pharmacological evidence show mu opioid receptors to be the most likely involved in the regulation of sexual behavior. The goal of this dissertation was to elucidate the role of endogenous opioid peptides in the regulation of male sexual behavior by addressing the following three specific aims. Specific aim 1 addressed when and where endogenous opioid peptides act during sexual behavior. This aim was investigated by examining in which brain regions mating-induced mu opioid receptor activation occurs and during which component of sexual behavior it occurs. Specific aim 2 addressed what the behavioral significance of mu opioid receptor activation is. The medial parvocellular Subparafascicular thalamic nucleus was the brain region chosen for examination of this aim. This region is part of the spinothalamic pathway important for the processing of sensory signals related to ejaculation. Sexual behavior was observed following pharmacological mu opioid receptor activation in the medial parvocellular Subparafascicular thalamic nucleus. Specific Aim 3 addresses which endogenous opioid peptide(s) is acting during male sexual behavior. Although three known ligands exist for mu opioid receptors, we chose to begin investigation of this aim by examining beta-endorphin. Activation of beta-endorphin neurons following various components of sexual behavior was analyzed. In addition, sexual behavior of beta-endorphin knockout mice was examined to determine any deficits due to the absence of beta-endorphin. Together, the data within this dissertation help to further our understanding of how endogenous opioid peptides are involved in the regulation of male sexual behavior.

Regulatory peptides represent the most diverse and versatile family of messenger molecules. They are produced by all living organisms from bacteria to mammals. They are involved in a wide variety of biological functions. Biologically active peptides and their receptors thus constitute an unlimited source of inspiration for the development of innovative drugs and cosmetics. The present eBook is a unique collection of research articles and reviews that provide a representative examplification of the latest progress in regulatory peptide research.

The interest in opioids such as morphine, the prototypical opioid ligand, has been maintained through the years. The identification of endogenous opioids and their receptors (mu, delta, kappa, and nociceptin), molecular cloning, and the elucidation of the crystal structures of opioid receptors represent key milestones in opioid research. The opioid system modulates numerous pharmacological responses, with therapeutic (i.e., analgesia) and detrimental side effects (i.e., addiction). The medical use and misuse of opioids have dramatically increased, leading to the 21st century opioid crisis. This book presents recent developments in opioid drug discovery, specifically in the medicinal chemistry and pharmacology of new ligands targeting the opioid receptors as effective and safe therapeutics for human diseases. Furthermore, it draws a special attention to advancing concepts and strategies in opioid drug discovery to mitigate opioid liabilities. The diversity among the discussed topics is a testimony to the complexity of the opioid system, which results from the expression, regulation, and functional role of ligands and receptors. The array of multidisciplinary research areas illustrates the rapidly developing basic research and translational activities in opioid drug discovery. This book will serve as a useful reference while also stimulating continued research in the chemistry and pharmacology of opioids and their receptors, with the prospect of developing improved therapies for human diseases, but also improving health and quality of life in general.