Sensory Mechanisms of the Spinal Cord Volume 1 Primary Afferent Neurons and the Spinal Dorsal Horn

The third edition of this monograph continues to have the goal of providing an overview of current thought about the spinal cord mechanisms that are responsible for sensory processing. We hope that the book is of value to both basic and clinical neuroscientists. Several changes have been made in the presentation, as well as additions because of the research advances that have been made during the past decade. Chapters 3 and 4 in the previous edition have been subdivided, and now the morphology of primary afferent neu­ rons of the dorsal root ganglia is described in Chapter 3 and the chemical neuroanatomy 4. The description of the dorsal hom in the previous Chapter 4 of these neurons in Chapter is now included in Chapter 5, and the chemical neuroanatomy of the dorsal hom in Chapter 6. Furthermore, discussions of the descending control systems have now been of Chapter 12. consolidated at the end The authors would like to express their appreciation for the help provided by several individuals. R.E.C. wishes to acknowledge the many things he learned about primary afferent neurons from conversations with Dr S. N. Lawson. He also thanks Lyn Shilling for her assistance with the typing. WDW thanks Dr Nada Lawand for her critical reading of parts of the manuscript, Rosaline Leigh for help with the manuscript, and Griselda Gonzales for preparing the illustrations.

1: Introduction.- Sensory Modalities and Channels.- Specificity versus Pattern Theories of Sensation.- Historical Perspective.- Specificity Theory.- Pattern Theory.- Gate Theory of Pain.- Supporting Evidence.- Molecular Basis of Specificity of Primary Afferent Neurons.- Sinclair’s Challenge and Evidence for Specificity from Microneurography.- Sensory Role of Single Tactile Afferents in Human Subjects.- Criticism of Microneurography Results.- Rebuttal of this Criticism.- Microneurography and Pain.- Somatosensory System Dualities.- Epicritic versus Protopathic Sensations.- Lemniscal versus Non-lemniscal Systems.- Large- versus Small-Fiber Systems.- Conclusions.- 2: Sensory Receptors and Peripheral Nerves.- Composition of Peripheral Nerves.- Sensory Receptors.- Cutaneous Receptors.- Cutaneous Mechanoreceptors.- Mechanoreceptors in the Glabrous Skin of the Primate Hand.- Cutaneous Displacement and Velocity Detectors.- SA I Receptors.- SA II Receptors.- Cutaneous Velocity Detectors.- FA I receptors.- Hair Follicle Receptors.- Field Receptors.- C Mechanoreceptors.- Cutaneous Transient Detectors.- FA II Receptors.- G1 Hair Follicle Receptors.- Sinus Hairs.- The Role of Growth Factors in the Regulation of Mechanoreceptors.- SA I (Merkel Cell) Endings.- FA I (Meissner Corpuscle) Receptors.- FA II (Pacinian Corpuscle) Receptors.- Hair Follicle Receptors.- Transduction in Mechanoreceptors.- Cutaneous Nociceptors.- A? Nociceptors.- C Nociceptors.- Transduction in Nociceptors.- Sensitization of Nociceptors.- Neurogenic Inflammation.- Peptidergic and Non-Peptidergic Nociceptors.- Nociceptors and Neurogenic Inflammation.- Interaction of Growth Factors with Nociceptors.- Inhibitory Interactions with Peripheral Cutaneous Nociceptor Endings.- Cutaneous Chemoreceptors Possibly Responsible for Itch.- Cutaneous Thermoreceptors.- Cold Receptors.- Warm Receptors.- Transduction in Thermoreceptors.- Muscle Receptors.- Stretch Receptors.- Muscle Spindles.- Golgi Tendon Organs.- Pressure-Pain Endings and Muscle Nociception.- Group III Muscle Afferents.- Group IV Muscle Afferents.- Sensitization of High Threshold Muscle Afferents.- Joint Receptors.- Joint Mechanoreceptors.- Slowly Adapting Joint Receptors.- Rapidly Adapting Joint Receptors.- Joint Nociceptors.- Sensitization of Joint Nociceptors.- Peptide Content of Fine Joint Afferents.- Joint Inflammation.- Role of Dorsal Root Reflexes in the Neurogenic Inflammation of Arthritis.- Visceral Receptors.- Visceral Mechanoreceptors.- Visceral Nociceptors.- Peptides in Visceral Afferents.- Growth Factors and Visceral Afferents.- Sensitization of Visceral Afferents.- Visceral Thermoreceptors.- Conclusions.- 3: Dorsal Root Ganglion Cells and their Processes.- Dorsal Root Ganglion Cell Bodies.- DRG Cell Classifications.- Cytologic and Size Classifications.- Myelination.- Axon Conduction Velocity.- Action Potentials and After Polarizations.- Classifications by Chemical Neuroanatomical Criteria.- Topographic Organization.- Innervation of Ganglion Cell Bodies, Pericellular Baskets.- Dorsal Root Ganglion Cell Processes.- Dermatomes.- Branching.- Ventral Root Afferent Fibers.- Spinal Cord.- Blind Fibers.- Looping Fibers.- Pial Fibers.- Function.- Segregation of Dorsal Root Fibers.- Conclusions.- 4: Chemical Anatomy of Dorsal Root Ganglion Cells.- Amines.- Catecholamines (CAs).- Histamine.- Serotonin.- Amino Acids.- Glutamate.- Aspartate.- GABA.- Glycine.- Channels.- Calcium Channels.- Sodium Channels.- Voltage-Gated Sodium Channels.- Cell Size.- Co-localizations.- ? Subunits.- Development.- Inflammation.- Peripheral Axotomy.- Nerve Growth Factor (NGF).- Peripheral Sensory Axons.- Non-voltage Gated Sodium Channels.- Enzymes.- Alkaline Phosphatase.- Carbonic Anhydrase (CA).- Cholinergic Enzymes.- ChAT.- ACHE.- Cytochrome Oxidase.- Fluoride-resistant Acid Phosphatase (FRAP).- Monoamine Oxidase.- Nitric Oxide (NO), Nitric Oxide Synthase (NOS) and NADPHd.- Ca++ Calmodulin Kinase II.- Other Kinases.- Hormones.- Corticotrophin Releasing Factor (CRF).- Insulin.- Peptides.- Angiotensin.- Atrial and Brain Natriuretic Peptide.- Bombesin.- Cholycystokinin (CCK).- Calcitonin Gene-related Peptide (CGRP).- Classification.- Age.- Development.- Co-localizations.- SP.- GAL.- SOM.- CCK.- VIP.- Bombesin, ENK, DYN, VIP, NT, and NPY.- FRAP.- Cysteine Proteases.- Amino Acids.- IB4.- Peripherin.- BDNF.- GDNF.- TrkA.- P75.- Experimental Manipulations or Disease.- Dorsal Rhizotomy.- Peripheral Nerve Lesions.- Inflammation.- Diabetes.- Hypoxia.- Hereditary Sensory Neuropathy.- Capsaicin.- Axonal Transport Blockers.- NGF Treatment.- Female Steroid Hormones.- Sympathectomy.- Dorsal Roots.- Periphery.- Somatic Innervation.- Visceral Innervation.- Endothelin (ET).- Galanin.- Nerve Lesions.- Inflammation.- Resiniferatoxin.- Axonal Transport Blockers.- Co-localizations.- CGRP.- SP.- VIP.- NPY.- 5-HT.- Glucocorticoid Receptors.- Dorsal Roots.- Neuropeptide FF (NPFF).- Neuropeptide Y (NPY), Polypeptide Y (PPY), and Peptide YY.- Peripheral Axotomy or Compression.- Trophic Factors.- Development.- Co-localizations.- Peripheral Innervation.- Neurotensin (NT).- Opioids.- Dynorphin (DYN).- Endomorphin.- Endorphin.- Enkephalin.- Nociceptin.- Oxytocin and Vasopressin.- Secretoneurin and the Chromagranins.- Somatostatin.- Co-localizations.- GDNF and Peripheral Axotomy.- Development.- Periphery.- Substance P (SP).- Segmental Levels.- Age and Development.- Co-localizations.- Tachykinins.- CGRP.- GAL.- SOM.- CCK.- ENKandDYN.- Bombesin, VIP, NT, and NPY.- FRAP.- NOS.- Glutamate.- IB-4.- 200 KD Neurofilament Protein.- Peripherin.- GDNF.- Opioid Receptors.- Experimental Manipulations.- Dorsal Rhizotomy.- Peripheral Nerve Lesions.- Inflammation.- Trophic Factors.- Adrenalectomy.- Resiniferatoxin.- Periphery.- Somatic Innervation.- Visceral Innervation.- VIP.- Proteins.- Calcium Binding Proteins.- Glutamate Transporters.- Reg-2.- Bone Matrix Proteins.- ?-arrestin.- Receptors.- Aminergic Receptors.- Adrenergic Receptors.- Dopamine Receptors.- Histamine Receptors.- 5-HT Receptors.- 5-HT1A Receptors.- 5-HT1B Receptors.- 5-HTlC Receptors.- 5-HT1D Receptors.- 5-HT1E Receptors.- 5-HT1F Receptors.- 5-HT2 Receptors.- 5-HT3 Receptors.- 5-HT4, 5-HT5, and 5-HT7 Receptors.- Amino Acid Receptors.- Glutamate Receptors.- Ionotropic Glutamate Receptors.- Metabotropic Glutamate Receptors.- GABA Receptors.- Glycine Receptors.- Cholinergic Receptors.- Nicotinic Receptors.- Muscarinic Receptors.- Hormone Receptors.- Androgen Receptors.- Estrogen Receptors.- Gender Differences.- Development.- Castration.- Glucocorticoid Receptors.- Insulin Receptors.- TRH Receptors.- Vitamin D Receptors.- Peptide Receptors.- Angiotensin Receptors.- Bombesin Receptors.- Bradykinin Receptors.- Cannabinoid Receptors.- CCK Receptors.- CGRP Receptors.- Endothelin (ET) Receptors.- Galanin Receptors (GALR).- Neuropeptide Y Receptors (Y-Rs).- Neurotensin Receptors (NT-R).- Neurokinin-1 Receptors (NKR1s).- NPFF Receptors.- Opioid Receptors.- MORs, DORs, and KORs.- Co-localizations.- Peripheral Axotomy.- Inflammation.- Development.- Periphery.- Endomorphin Receptors.- Endorphin Receptors.- Opioid-like Receptor 1 (ORL1).- Sigma Receptors.- Oxytocin and Vasopressin Receptors.- Somatostatin Receptors.- Vasoactive Intestinal Polypeptide (VIP) Receptors.- Purinergic Receptors or Purinoceptors.- Adenosine Receptors.- ATP (P) Receptors.- P2X Purinoceptors.- P2Y Purinoceptors.- Vanilloid Receptors (VRs).- Conclusions.- 5: Structure of the Dorsal Horn.- Lamina I.- Cell Types.- Classic Types: Marginal and Smaller Cells.- Modern Types.- Primary Afferent Input into Lamina I.- The Marginal Plexus.- Large versus Small Fibers.- A? versus C Fibers.- Propriospinal versus Primary Afferent Fibers.- Cutaneous, Muscular, and Visceral Afferent Input.- Neuropil Organization.- Lamina II (The Substantia Gelatinosa).- Cell Types.- Classic Cell Types.- Limiting (Limitrophe, Border) Cells.- Central Cells.- Funicular Cells.- Short-Axoned Cells.- The Gelatinosa as