Historical Background.- Epidemiology of the Burden of Chronic Itch.- Neurophysiology and Itch Pathways.- Brain Mechanisms of Chronic Itch.- Mouse and Human Models of Itch. Transient Receptor Potential Channels and Itch.- Cytokines and Itch.- Role of Mrgpr Family of Receptors and Itch.- Protease-activated Receptor Agonists and Itch.- VGLUT2-dependent Sensory Neurons and Itch.- Identification and Characterization of Spinal Inhibitory Neurons That Inhibit Itch.- Noradrenergic Itch Transmission in the Spinal Cord.- NK-1 Antagonists and Itch.- Cannabinoids and Itch.- Antihistamines and Itch.- Targeting Itch with Ligands Selective for k Opioid Receptors.- Neuraxial Opioid-induced Scratching and Its Pharmacological Antagonism.- Topical Therapies.- Allergic Itch in Dogs.
Basic research on the pharmacology of itch has exploded in the wake of two very influential papers that were published in Nature (2007) and Science (2009). Long overlooked as a milder form of pain, itching has rapidly gained a new appreciation in both research and clinical communities because of its complexity and its negative effects on the quality of life of the distressed patients. Like pain, not all itches are the same. Unlike pain, there are no standard drugs equivalent to aspirin and morphine. Epidemiological studies emphasize the high incidence and economic costs of itch (pruritus). It is the most prevalent symptom of a wide variety of allergic and inflammatory skin conditions (e.g., psoriasis, atopic dermatitis), is associated with several systemic diseases (e.g., chronic kidney and liver disease), and occurs in patients undergoing hemodialysis, spinal administration of opioids, and in those suffering from AIDS. The reader will learn about the multiple pathways for itch and their interactions with pain. The relationship between these closely related, yet distinct sensory phenomena, will be emphasized. Both itch and pain use several common molecules to send signals to the brain. Thus, drugs that have been, and are being, developed as analgesics may also attenuate intractable itch. This has been an exciting and very necessary turn of events since traditional H-1 receptor antagonists are ineffective in blocking the pruritus associated with kidney failure and cholestasis. The clinical chapters will provide insights into contemporary treatment regimens for pruritus in different human scenarios.