Advances in itch research have elucidated differences between itch and pain but have also blurred the distinction between them. There has been 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 lymphoma, 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.

Contents

• Series Preface
• Preface
• Editors
• Contributors
• 1. Itch Hypotheses: From Pattern to Specificity and to Population Coding
  Hermann O Handwerker.
• 2. Epidemiology of Itch
  Elke Weisshaar and Uwe Matterne.
  • 2.1 PREFACE/STARTING POINT
  • 2.2 IMPORTANT EPIDEMIOLOGICAL PARAMETERS AND HOW TO OBTAIN THEM
  • 2.3 INTRODUCTION
  • 2.4 PRURITUS IN SPECIFIC AGE GROUPS
  • 2.5 PRURITUS IN SPECIFIC DISEASES
  • 2.6 PRURITUS IN THE GENERAL POPULATION
  • 2.7 NEW DEVELOPMENTS AND CURRENT RESEARCH
  • 2.8 CONCLUDING REMARKS
  • REFERENCES
• 3. Atopic Dermatitis
  Ulf Darsow, Ulrike Raap, and Sonja Ständer.
  • 3.1 ATOPIC ECZEMA
  • 3.2 ATOPIC ITCH
  • 3.3 FEATURES OF ATOPIC ITCH SHOWN WITH SCALES AND QUESTIONNAIRES
  • 3.4 MECHANISM OF ATOPIC ITCH
  • 3.5 NERVES AND ITCH
  • 3.6 SUBSTANCE P AND ITCH
  • 3.7 EOSINOPHILS AND NERVES IN ATOPIC DERMATITIS
  • 3.8 EOSINOPHILS AND NEUROTROPHINS/NEUROPEPTIDES IN THE REGULATION OF ITCH
  • 3.9 IL-31 AND ITCH IN ATOPIC DERMATITIS
  • 3.10 THERAPY OF AD ITCH
  • 3.11 ANTI-INFLAMMATORY THERAPIES
  • 3.12 ANTIHISTAMINES
  • 3.13 TARGET-SPECIFIC THERAPY
  • REFERENCES
• 4. Clinical Aspects of Itch: Psoriasis
  Adam Reich and Jacek C Szepietowski.
  • 4.1 INTRODUCTION
  • 4.2 PREVALENCE, SEVERITY, AND CLINICAL PRESENTATION OF ITCH IN PSORIASIS
  • 4.3 MECHANISM OF ITCH IN PSORIASIS
  • 4.4 BURDEN OF ITCH IN PSORIASIS
  • 4.5 TREATMENT OF ITCH IN PSORIASIS
  • REFERENCES
• 5. Pruritus in Renal Disease
  Thomas Mettang.
  • 5.1 INTRODUCTION
  • 5.2 CLINICAL FEATURES OF CKD-aP
  • 5.3 TOPICAL TREATMENT
  • 5.4 µ-OPIOID RECEPTOR ANTAGONISTS
  • 5.5 κ-OPIOID RECEPTOR AGONISTS
  • 5.6 OTHER MEDICAL TREATMENT OPTIONS
  • REFERENCES
• 6. Pruritus of Cholestasis
  Nora V Bergasa.
  • 6.1 PATHOGENESIS OF THE PRURITUS OF CHOLESTASIS
  • 6.2 INDIVIDUAL PREDISPOSITION TO EXPERIENCE PRURITUS BY PATIENTS WITH CHOLESTASIS
  • 6.3 RECEPTORS SPECIFICITY IN THE MEDIATION OF OPIOID-INDUCED PRURITUS
  • 6.4 PRURITUS OF CENTRAL ORIGIN
  • 6.5 SCRATCHING ACTIVITY IN PATIENTS WITH THE PRURITUS OF CHOLESTASIS: LESSONS FROM BEHAVIORAL STUDIES
  • 6.6 TREATMENT OF THE PRURITUS OF CHOLESTASIS
  • REFERENCES
• 7. Neuropathic Itch
  Anne Louise Oaklander.
  • 7.1 BACKGROUND AND INTRODUCTION
  • 7.2 DIAGNOSIS AND MEASUREMENT
  • 7.3 CLINICAL NI SYNDROMES
  • 7.4 MANAGING AND TREATING NEUROPATHIC ITCH
  • 7.5 CONCLUSIONS AND FUTURE DIRECTIONS
  • REFERENCES
• 8. Pruritus in Cutaneous T-Cell Lymphomas
  Laurent Misery.
  • 8.1 CUTANEOUS T-CELL LYMPHOMAS
  • 8.2 PRURITUS IN CTCL
  • 8.3 PATHOPHYSIOLOGY
  • 8.4 THERAPEUTICS
  • 8.5 CONCLUSION
  • REFERENCES
• 9. Pruriceptors
  Matthias Ringkamp and Richard Meyer.
  • 9.1 INTRODUCTION
  • 9.2 PARALLEL PATHWAYS FOR HISTAMINERGIC AND NONHISTAMINERGIC ITCH
  • 9.3 ROLE OF C-FIBERS IN ITCH SENSATION
  • 9.4 ROLE FOR A-FIBERS IN ITCH SENSATION
  • 9.5 CONCLUSIONS
  • REFERENCES
• 10. Peripheral Neuronal Mechanism of Itch: Histamine and Itch
  Robin L Thurmond, Kayvan Kazerouni, Sandra R Chaplan, and Andrew J Greenspan.
  • 10.1 INTRODUCTION
  • 10.2 ANTIHISTAMINES AND HISTAMINE RECEPTORS
  • 10.3 HISTAMINE-INDUCED SKIN PRURITUS
  • 10.4 WHICH HISTAMINE RECEPTORS MEDIATE PRURITUS?
  • 10.5 OCULAR AND NASAL PRURITUS
  • 10.6 ANTIHISTAMINES IN CLINICAL PRACTICE
  • 10.7 CONCLUSIONS AND FUTURE DIRECTIONS
  • REFERENCES
• 11. Role of PAR-2 in Neuroimmune Communication and Itch
  Cordula Kempkes, Joerg Buddenkotte, Ferda Cevikbas, Timo Buhl, and Martin Steinhoff.
  • 11.1 INTRODUCTION
  • 11.2 PROTEASE-ACTIVATED RECEPTORS AND PROTEASES
  • 11.3 PAR-2 EXPRESSION IN THE SKIN
  • 11.4 FUNCTIONAL ROLE OF PAR-2 IN ITCH
  • 11.5 DIFFERENCES BETWEEN PAR-2- AND MrgprC11-INDUCED ITCH
  • 11.6 FUNCTIONAL ROLE OF PAR-2 IN NEUROGENIC INFLAMMATION
  • 11.7 ROLE OF PAR-4 IN ITCH
  • 11.8 CONCLUSIONS AND FUTURE DIRECTIONS
  • REFERENCES
• 12. Mrgprs as Itch Receptors
  Benjamin McNeil and Xinzhong Dong.
  • 12.1 INTRODUCTION
  • 12.2 DISCOVERY OF THE Mrgprs
  • 12.3 EXPRESSION OF Mrgprs
  • 12.4 GENERATION OF Mrgpr KNOCKOUT ANIMALS
  • 12.5 ROLE OF Mrgprs IN ITCH IN MICE
  • 12.6 Mrgpr SIGNALING PATHWAYS
  • 12.7 BAM8-22, AN Mrgpr AGONIST, INDUCES ITCH IN HUMANS
  • 12.8 DIFFERENCES BETWEEN ITCH RECEPTORS AND OLFACTORY RECEPTORS
  • 12.9 OTHER Mrgprs
  • 12.10 DIMERIZATION
  • 12.11 QUESTIONS
  • REFERENCES
• 13. Role of Interleukin-31 and Oncostatin M in Itch and Neuroimmune Communication
  Ferda Cevikbas, Cordula Kempkes, Timo Buhl, Christian Mess, Joerg Buddenkotte, and Martin Steinhoff.
  • 13.1 INTRODUCTION
  • 13.2 CONCLUSIONS AND FUTURE DIRECTIONS
  • REFERENCES
• 14. Toll-Like Receptors and Itch
  Tong Liu and Ru-Rong Ji.
  • 14.1 INTRODUCTION
  • 14.2 TLRs, THE LIGANDS, AND INTRACELLULAR SIGNALING
  • 14.3 TLRs IN CHRONIC PAIN
  • 14.4 TLRs IN ACUTE AND CHRONIC ITCH
  • 14.5 FUTURE PERSPECTIVES AND CLINICAL SIGNIFICANCE
  • CONFLICT OF INTEREST
  • REFERENCES
• 15. Lipid Mediators and Itch
  Tsugunobu Andoh and Yasushi Kuraishi.
  • 15.1 INTRODUCTION
  • 15.2 ARACHIDONIC ACID METABOLITES
  • 15.3 PLATELET-ACTIVATING FACTOR
  • 15.4 LYSOPHOSPHATIDIC ACID
  • 15.5 SPHINGOLIPIDS
  • REFERENCES
• 16. Role of Transient Receptor Potential Channels in Acute and Chronic Itch
  Sarah R Wilson and Diana M Bautista.
  • 16.1 INTRODUCTION
  • 16.2 TRPV1
  • 16.3 TRPV1-EXPRESSING AFFERENTS AND ACUTE ITCH
  • 16.4 TRPA1 AND HISTAMINE-INDEPENDENT ITCH
  • 16.5 TRPV3 AND KERATINOCYTE-MEDIATED ITCH PATHWAYS
  • 16.6 TRPM8 IN INHIBITION OF ITCH
  • 16.7 CONCLUSIONS AND FUTURE PROSPECTS
  • REFERENCES
• 17. Sensitization of Itch Signaling: Itch Sensitization—Nerve Growth Factor, Semaphorins
  Mitsutoshi Tominaga and Kenji Takamori.
  • 17.1 INTRODUCTION
  • 17.2 SKIN DISEASES WITH ITCH INVOLVING EPIDERMAL NERVE FIBERS
  • 17.3 ROLES OF NGF AND Sema3A IN EPIDERMAL NERVE FIBERS
  • 17.4 NGF AND Sema3A AS ANTIPRURITIC TARGETS
  • 17.5 CONCLUSION
  • REFERENCES
• 18. Peripheral Opioids
  Paul L Bigliardi and Mei Bigliardi-Qi.
  • 18.1 INTRODUCTION
  • 18.2 OPIOID RECEPTORS IN SKIN
  • 18.3 OPIOID RECEPTORS IN SKIN DISEASES
  • 18.4 PERIPHERAL µ-OPIOID RECEPTORS (MOR) AND ITCH
  • 18.5 PERIPHERAL κ-OPIOID RECEPTORS (KOR) AND ITCH
  • 18.6 PERIPHERAL δ-OPIOID RECEPTORS (DOR) AND ITCH
  • 18.7 CONCLUSIONS
  • REFERENCES
• 19. Spinal Coding of Itch and Pain
  Tasuku Akiyama and E Carstens.
  • 19.1 INTRODUCTION
  • 19.2 RELATIONSHIP TO PAIN
  • 19.3 PERIPHERAL PATHWAYS
  • 19.4 SPINAL NEUROTRANSMITTERS
  • 19.5 PRURITOGEN-RESPONSIVE SPINAL AND MEDULLARY DORSAL HORN NEURONS
  • 19.6 MODULATION OF ITCH BY NOXIOUS COUNTERSTIMULI
  • 19.7 SENSITIZATION OF ITCH-SIGNALING PATHWAYS
  • 19.8 SPECIFICITY VERSUS POPULATION CODING THEORIES OF ITCH AND PAIN
  • 19.9 CONCLUSION
  • REFERENCES
• 20. Spinal Microcircuits and the Regulation of Itch
  Sarah E Ross, Junichi Hachisuka, and Andrew J Todd.
  • 20.1 PUTATIVE SPINAL MICROCIRCUITS INVOLVED IN THE MODULATION OF ITCH
  • 20.2 ROLE OF GRPR NEURONS AND ITCH
  • 20.3 BRIEF OVERVIEW OF NEURONAL ORGANIZATION AND CIRCUITRY WITHIN THE DORSAL HORN
  • 20.3.1 Projection Neurons
  • 20.3.2 Interneurons
  • REFERENCES
• 21. Itch Modulation by VGLUT2-Dependent Glutamate Release from Somatic Sensory Neurons
  Qiufu Ma.
  • 21.1 INTRODUCTION
  • 21.2 DISCOVERY OF VGLUT1-3 AND THEIR EXPRESSION IN DRG
  • 21.3 VGLUT2-DEPENDENT GLUTAMATE RELEASE FROM DRG NEURONS IS REQUIRED TO SENSE ACUTE AND CHRONIC PAIN
  • 21.4 ITCH INHIBITION BY VGLUT2-DEPENDENT GLUTAMATE RELEASE FROM DRG NEURONS
  • 21.5 WHAT IS THE NEUROTRANSMITTER BASIS OF ITCH?
  • 21.6 HOW IS ITCH INHIBITED BY VGLUT2-DEPENDENT GLUTAMATE RELEASE FROM DRG NEURONS?
  • 21.7 POPULATION CODING OF ITCH VERSUS PAIN OR OTHER SENSORY MODALITIES
  • 21.8 CONCLUDING REMARKS
  • REFERENCES
• 22. Ascending Pathways for Itch
  Steve Davidson, Hannah Moser, and Glenn Giesler.
  • 22.1 PSYCHOPHYSICAL STUDIES OF SCRATCH
  • 22.2 INHIBITION ON INTERNEURONS IN THE SPINAL CORD
  • 22.3 PRURICEPTIVE STT NEURONS ARE INHIBITED BY SCRATCHING DURING ITCH
  • 22.4 SCRATCHING ON THE SKIN, ITCHING IN THE BRAIN
  • 22.5 CIRCUITRY OF RELIEF
  • REFERENCES
• 23. Brain Processing of Itch and Scratching
  Hideki Mochizuki, Alexandru D.P Papoiu, and Gil Yosipovitch.
  • 23.1 OVERVIEW
  • 23.2 ITCH TRANSMISSION TO THE SUPERIOR CENTERS OF THE CENTRAL NERVOUS SYSTEM
  • 23.3 BRAIN AREAS ACTIVATED DURING ITCH PROCESSING
  • 23.4 DIFFERENTIAL CEREBRAL PROCESSING OF HISTAMINE AND COWHAGE ITCHES
  • 23.5 CHARACTERISTICS OF THE BRAIN PROCESSING OF PRURITUS IN CHRONIC ITCH CONDITIONS
  • 23.6 CONTAGIOUS ITCH
  • 23.7 CRAVING FOR ITCH RELIEF AND ITS CEREBRAL MECHANISMS
  • 23.8 BRAIN PROCESSING OF SCRATCHING
  • 23.9 INSIGHTS FOR A THERAPEUTIC STRATEGY TO RELIEVE ITCH DERIVED FROM BRAIN IMAGING STUDIES
  • REFERENCES
• 24. Central Nervous Processing of Itch and Pain
  Clemens Forster and Hermann O Handwerker.
  • 24.1 BRAIN ACTIVATION STUDIES OF PAIN AND ITCH: SIMILARITIES AND DIFFERENCES
  • 24.2 CONNECTIVITY STUDIES: A NEW OPTION FOR COMPARING CENTRAL ITCH AND PAIN PROCESSING
  • REFERENCES
• 25. Roles of Central Opioid Receptor Subtypes in Regulating Itch Sensation
  Mei-Chuan Ko.
  • 25.1 INTRODUCTION
  • 25.2 OPIOID RECEPTOR SUBTYPES IN THE CENTRAL NERVOUS SYSTEM
  • 25.3 EVIDENCE OF CENTRAL MU OPIOID RECEPTORS INVOLVED IN ITCH
  • 25.4 SELECTIVITY AND EFFICACY OF MOP-MEDIATED ITCH
  • 25.5 POTENTIAL OF KOP RECEPTOR AGONISTS AS ANTIPRURITICS
  • 25.6 CONCLUSIONS
  • REFERENCES
• 26. Sensitization for Itch
  Martin Schmelz.
  • 26.1 CHEMICALLY INDUCED ITCH
  • 26.2 PERIPHERAL SENSITIZATION
  • 26.3 CENTRAL SENSITIZATION
  • 26.4 PERSPECTIVES
  • REFERENCES