Index. B β-alanine cellular level, 80 DRG neurons, 80 heat-sensitive neurons, 82 itch-sensing neurons, 75 MrgprD, 80 muscle building, 79 water, 79, 80

Transcription

1 Index A ACC. See Anterior cingulate cortex (ACC) Acute itch, 339 Acute pruritus aprepitant, erlotinib, 247 paraneoplastic pruritus, 248 pruritic drug reactions, 247 AD. See Atopic dermatitis (AD) Α1-adrenoceptors, Α2-adrenoceptors, 213 AEW-treated mice, 228 Agonist kappa opioid receptor, nalbuphine and butorphanol, 322 neuraxial opioid-induced pruritus, Allergic conjunctivitis, 266, 267, 272 Allergic rhinitis allergen-induced, mice, 272 H 1 R antihistamines, 259, 264 nasal and pharyngeal pruritus, 265 Alpha-adrenoceptor α1-adrenoceptors, α2-adrenoceptors, 213 agonists, Anaesthetics, 342 Analgesics opioid, 319, 321 spinal, 319, 325 Antagonist histamine H1 receptor, 328 mu opioid receptor, neurokinin receptor, serotonin 5-HT3 receptor, 325, Anterior cingulate cortex (ACC), 59 65, 67, 224 Anticonvulsants, 339 Antidepressants, Antihistamines, 344 Antipruritics, 324 Aprepitant adverse events, antipruritic effects, Arterial spin labeling (ASL), 66, 68 Arylacetamide enadoline, 296 itch and visceral pain, 305 ASL. See Arterial spin labeling (ASL) Atopic dermatitis (AD) cathepsin S overexpression, 183, 222 in dogs (see Atopic itch in dogs) histamine receptor, 259 H 4 R, 273 IL-4 and IL-13, 171 IL-31 mrna, 166 intrinsic vs. extrinsic, 274 keratinocytes, 182, 274 protease-related mutant mice, 222 pruritic skin, 267 stratum corneum, 179 TH 2 -mediated immune response, 166 Atopic itch in dogs classification, 359 etiology, modeling and pharmacology (see Canine atopic itch) B β-alanine cellular level, 80 DRG neurons, 80 heat-sensitive neurons, 82 itch-sensing neurons, 75 MrgprD, 80 muscle building, 79 water, 79, 80 # Springer-Verlag Berlin Heidelberg 2015 A. Cowan, G. Yosipovitch (eds.), Pharmacology of Itch, Handbook of Experimental Pharmacology 226, DOI /

2 372 Index Basic helix-loop-helix (bhlh) transcription factor Bhlhb5, dorsal horn, 194 Benzomorphan, 295, 298 Bhlhb5, Bhlhe22. See Bhlhb5 B5-I neurons Bhlhb5 / mice, counter stimuli, 202, 203 direct synaptic input, 202 inhibition of itch, 197 kappa agonists inhibit itch (see Kappa agonists) kappa opioid dynorphin, spinal interneurons population, Biting, Bombesin BB 2 receptor, 213 GRPR, 47 icv, 295 Bovine adrenal medulla 8-22 (BAM8-22) peptide and chloroquine, 76 DRG neurons, 78 mouse and human Mrgprs, 75 pruritogens, 77, 81, 82 Brachioradial pruritus, 250 Brain, 224 Butorphanol 14-hydroxymorphinan, 305 inflammatory skin/systemic diseases, 306 lipophilic butorphanol (Stadol NS ), 306 nalbuphine ER, 306 Byzantine period, 4 5 C Calamine, 342 Calcium signaling, Canine atopic itch cyclosporine efficacy, mechanism of action, 361 glucocorticoids efficacy, mechanism of action, 360 Janus kinase (JAK) inhibitors efficacy, 363 mechanism of action, 363 modeling flea allergic pruritus dog model, HDM allergic pruritus dog model, pruritus induction by single substances, type 1 antihistamines efficacy, mechanism of action, 362 Cannabinoids, 344 Canonical TRP channels, 101, Capsaicin, , CDLQI. See Children s Dermatology Life Quality Index (CDLQI) C-fibres, 339, 341 Chanzymes, 101 Chemokines immunomodulators, 165 inflammatory, 169 interleukin-8 (IL-8), 172 messenger molecules, 165 Children s Dermatology Life Quality Index (CDLQI), 25 Chloroquine, 75 allergic response, 76 antimalarial drug, 76 β-alanine, 75 and BAM8-22, 76 pruritogens, 81, 82 Cholestatic pruritus, Chronic cholestatic liver disease, 267 Chronic itch. See also Chronic itch, management causes dermatological, 339 neuropathic, 339 psychogenic, 339 systemic, 339 immunosuppressants apremilast, 352 biologic agents, 352 dapsone, 352 methotrexate, mycophenolate mofetil (MMF), 351 oral, 351 kappa agonists, 200 keratinocytes, neurogenic itch, 83 neuropathic itch, 83 pruritoceptive itch, 83 psychogenic itch, 83 Chronic itch, management brain perfusion measurements, 68 processing, 62 64

3 Index 373 target, contagious itch, cortical regions, fmri, 59 histamine and cowhage, MEG, 59 PAG role, 65 PET, 59 prefrontal and limbic control, relief and cerebral mechanisms (see Craving) transmission CNS, 59 cortex, 59 Chronic pruritus, 200, 238, See also Chronic itch antipruritic effect of aprepitant, brachioradial pruritus, 250 CTCL, 250 NKR1, 248 therapies, Claustrum, 60, 62, 63, 65, 225 Complex regional pain syndrome (CRPS), 243 Compound 48/80 antinociceptive agents, 297 enadoline, 297, 298 histamine H-1 and H-4 receptors, 299 ICI 204,297, 299, 300, 448 JNJ , 299 naloxone, 297 norbni, 297 potential antipruritic agents, 297 Swiss Webster mice, 297 Contagious itch atopic dermatitis, 67 brain imaging, 66, 67 central mechanisms, 66 insula and basal ganglia, 67 scratching, 66 Corticotropin-releasing hormone receptor-1 (CRHR-1), 243 Counterstimulus, 209 CR845, 307 Craving brain regions, 64 fmri, 64 PFC, 64, 65 tactile stimuli, 64 ventral tegmentum (VTA), 65 vice, 65 CRHR-1. See Corticotropin-releasing hormone receptor-1 (CRHR-1) CRPS. See Complex regional pain syndrome (CRPS) CTCL. See Cutaneous T-cell lymphoma (CTCL) Cutaneous drug reaction, 23 Cutaneous T-cell lymphoma (CTCL), 249, 250, 267 Cytokines histamine, 181 H 4 R antagonists, 274 IL-4 and IL-13, interleukin-2 (IL-2), interleukin-6 (IL-6), 171 interleukin-31 (IL-31), keratinocytes, 179, 182 messenger molecules, 165 oncostatin M (OSM), thymic stromal lymphopoietin (TSLP), 170 TNF Alpha, D DAMPs. See Danger-associated molecular patterns (DAMPs) Danger-associated molecular patterns (DAMPs), 137, Darier s disease (DD), 114 Delta opioid receptor (DOP), 319 Dermatologic disorders, 17 Dermatology Life Quality Index (DLQI), 25, Descending noradrenergic system, DLQI. See Dermatology Life Quality Index (DLQI) Dogs classification of itch, 359 etiology of itch, modeling and pharmacology of itch (see Canine atopic itch) Dorsal horn, 142 α1-adrenoceptor-mediated inhibition, 213 Bhlhb5, 196 capsaicin-induced glutamate, 213 C-fiber, 213 glycine and GABA activity, 201 interneurons, 194 itch regulation, NK1 receptors, 241 noradrenaline, 211, 214 sensory neurons, 180 Dorsal root ganglia (DRG), , 153 histamine-evoked calcium signals, 183 neuropeptides, 185

4 374 Index Dorsal root ganglia (DRG) (cont.) somatosensory neurons, 180 Dorsal spinal cord, DRG. See Dorsal root ganglia (DRG) DRG neurons β-alanine, 79 chloroquine, 77 GPCR, 73 intensity theory, 81 Mrgpr, 77 scratching response, 79 Venn diagram, 74 Drugs antidepressants, gabapentin and pregabalin, 349 kappa-opioid agonists, 350 mu-opioid antagonists, 350 neurokinin-1 inhibitors, 350 thalidomide, 351 Dynorphin, 158, 198, 199 E Eczema Area and Severity Index (EASI), 245 EGF. See Epidermal growth factor (EGF) EKC. See Ethylketocyclazocine (EKC) Emollients, Endotoxins (lipopolysaccharide), 137 End-stage renal disease (ESRD), 21, 25, 30, 60, 62, 63, 66 Epidermal growth factor (EGF), 112 ESRD. See End-stage renal disease (ESRD) Ethylketocyclazocine (EKC), 294, 295, 298 F Flea allergic pruritus dog model, Functional magnetic resonance imaging (fmri), 58, 59, 63 65, 68 G GABAergic interneuron, 210, Galanin, 197, 198 Gastrin-releasing peptide (GRP), 153, neurotransmitter, 295 secondary spinal cord neurons, 47 Gastrin-releasing peptide receptor (GRPR), 93, 153, , 318 lamina I, 93 μ-opioid receptor, 93 GDNF. See Glia-derived neurotrophic factor (GDNF) Glia, Glia-derived neurotrophic factor (GDNF), 44, 45, 98 Glucocorticoids, 343 Glycinergic interneuron, 210, GPCR. See G protein-coupled receptor (GPCR) G protein-coupled receptor (GPCR), 73, 75, 96, 143, 225, 362 TLRs, 143 TRP channels, 96 Grp. See Gastrin-releasing peptide (Grp) GRPR. See Gastrin-releasing peptide receptor (GRPR) 5 0 -guanidinonaltrindole (5 0 -GNTI) delta opioid receptors, 302 GRP, 303 McN-A-343, 303 muscarinic M-1 receptors, 303 RC-3095, 303 scratching, 302 Sprague Dawley rats, 302 H Histamine antihistamines, 95 binding affinities, C-fibers, 261 description, 258 GPCR super-family, 96 H 1 R(see Histamine H 1 receptor (H 1 R)) H 2 R, H 3 R, H 4 R, H1 receptor antagonists, 328 itch sensation, 260, 261 ligands, 259 MrgprA3-expressing neurons, 261 pruritus, 261 receptors, 258 substance P (SP) release, 97 TRPV1-deficient mice, 261 Histamine H 1 receptor (H 1 R) allergic rhinitis, bilastine, 264, 265 blockade, categories, 262 cetirizine, 265 clinical studies, 263, 264 expression, 261 fexofenadine, intradermal injection, 262

5 Index 375 levocetirizine and desloratadine, 263, 264 mosquito bites, 265 nasal itch, 265 ocular administration, pruritic diseases, 267 psoriasis symptoms, 267 urticaria, Histamine H 2 receptor (H 2 R) antagonist chlorpheniramine, 268 Cochrane review, enterochromaffin-like cells, 268 gastric acid secretion, ranitidine, 268 Histamine H 3 receptor (H 3 R) antagonism, 270 antagonists, in nervous system, 269 physiological functions, role in, 269 Histamine H 4 receptor (H 4 R) anti-inflammatory activity, 271 discovery, 270 expression, extrinsic atopic dermatitis, intrinsic atopic dermatitis, 274 JNJ , physiological function, 271 preclinical evidence, mechanisms, 273, 274 preclinical studies, 271 House dust mite (HDM) allergic pruritus dog model, I Icv. See Intracerebroventricular (icv) IFSI. See International Forum for the Study of Itch (IFSI) Inflammatory mediators bradykinin, 99 cytokines and interleukins (ILs), inflammatory hyperalgesia, 99 PGD2, 99 prostaglandins PGE1 and PGE2, 99 Insula and ACC, 59, 60 brain regions, 67 claustrum, 60 ESRD, 60 histamine-induced itch, 62 itch processing, 65 pain, 60 scratch, triggering, 67 Intensity theory, 81 Interleukin-2 (IL-2), Interleukin-4 (IL-4), Interleukin-6 (IL-6), 171 Interleukin-8 (IL-8), 172 Interleukin-13 (IL-13), Interleukin-31 (IL-31) atopic dermatitis, IL-31R, 166 keratinocytes, 169 pruritus, 168 TH 2 cells, 165 International Forum for the Study of Itch (IFSI), 16, 17, 24, 359 Intracerebroventricular (icv) bombesin-induced scratching, 295 ddy mice, 302 Itch(ing) acute, 339 B5-I neurons (see B5-I neurons) black stools and vomiting, 4 chronic, 339, C nerve fibres, 11 counter stimuli, cutaneous symptom, 8 cutaneous transmission, definition, description, 192 dorsal spinal cord, glutamate, 193 nervous system decode somatosensory, 192, 193 neurosis, 9 non-histaminergic pathway, 11 opioid receptor, 201 peripheral pathways painful and non-painful stimuli, interactions, perspectives, 50 sensitization, specificity, spinal processing, teleological implications, 40 phototherapy, 353 revolution, 12 and scabby scalp, 6 science, 9 10 scratching, 192 senilis, 8 sensation brain nerves, 73 IgE receptor, 84 secondary cell types, 83 somatosensation, 73 topical therapies, 339

6 376 Index Itch(ing) (cont.) transcription factor Bhlhb5, types neurogenic itch, 90, 95 neuropathic itch, 90, 95 pruriceptive itch, 90, 94 psychogenic itch, 90, 95 varicose veins, 10 vglut2, somatosensation, 193 J JDTic, 301, K Kallikrein (KLK), 182, Kappa agonists chronic pruritus, 200 inhibit itch, morphine-induced itch, monkeys, 201 Kappa opioid receptor (KOR), asimadoline, 306 butorphanol and nalbuphine, compound 48/80, CR845, 307 diarylacetamide, 306 dynorphin and spinal B5-I interneurons, GNTI, G protein-coupled/protease activated receptors, 308 irritable bowel syndrome, 306 itch/scratch (see Scratching) molecular processes, mood disorders and cocaine addiction, 307 nalfurafine, norbni, sensory nerve fibers, 306 zyklophin, Kappa opioid receptor (KOP) agonists, 319, Kappa opioids, 65 Keratinocytes, cell-cell signaling factors, 178, 179 and chronic itch, itch transmission, 178 neuronal modulation, 185 pruriceptors, 181 sensory neurons direct interactions, and immune cells, 179, 180 indirect interactions, somatosensory neuron, 180, 181 skin and itch stimuli detection dermal dendritic, 179 Langerhans cells, 179 macrophages, 179 sensory nerves and immune cells, 179, 180 somatosensory neuron, 180, 181 KOP. See Kappa opioid receptor (KOP) KOR. See Kappa opioid receptor (KOR) L Labeled-line theory, 81, 82, 91 Locus coeruleus, 211, 212, 214 M Magnetoencephalography (MEG), 58 Mas-related G-protein-coupled receptor B4 (MrgprB4), 42 Mas-related G-protein-coupled receptors (Mrgprs), 92, 168 DNA screening, 73 DRG neurons, heterologous cells, 74 human and mouse genome, 74 itch-mediating neurons, molecular markers, itch receptors, ligands and agonists, SNSR, 74 subfamilies, 73 Mast cells, , 248 Medical history diagnosis, 5 humoural pathology, 4 summer fevers, 4 symptoms, 4 Medieval medicine, 6 7 Menthol, , 341 Molecular markers, itch-mediating neurons MrgprA3, MrgprD, 82 Mrgprs, role of, Monkey intravenous ketorolac and nalmefene, effects, intravenous ondansetron, effects, 327 neuraxial opioid-induced scratching, MOP. See Mu opioid receptor (MOP) antagonists

7 Index 377 M-opioid receptors, 48 Mouse, 224, 230 behavior, 294, genome, 73, 74 and human, 75 mammalian peptides, 73 Mrgpr genes, 76 nociceptors, 73 Mrgprs as itch receptors MrgprA3, MrgprC11, MrgprD, Mu opioid receptor (MOP) antagonists, 318, N Nalbuphine. See Butorphanol Nalfurafine (TRK-820) ADL , 305 muscarinicm-1 receptors, 305 SP itch model, 304 Remitch capsules, 304 uremic pruritus, 305 National Ambulatory Medical Care Survey, 19 Natriuretic peptide receptor A (Npr1), Natriuretic polypeptide b (Nppb), 93, Nerve growth factor (NGF), 44, 49, 50, 98, 103, 108, , 185, 186, 227, 228, AD, 245 capsaicin application, 243 histamine-induced itch, 228 keratinocytes, 185 plasma levels, 186 Neural pathways. See Itch(ing) Neuraxial opioid-induced itch clinical applications, intrathecal morphine, 321 mechanisms animal models with translational values, cellular basis, 319 molecular basis, 318 pharmacological antagonism by non-opioid ligands, by opioid-related ligands, side effects, Neurogenic inflammation, 184, 185 Neurogenic itch, 95 Neuroimaging of itch. See Chronic itch, management Neurokinin-1 receptor (NK1R), Neuronal nitric oxide synthase (nnos), 197, 198 Neuropathic and psychosomatic diseases, 19 Neuropathic itch, 95 Neuropeptides, Neurotransmitters, 154 Neurotrophin 4 (NT4), 50, 98, 103 Neurotrophins, 98 NGF. See Nerve growth factor (NGF) NHP. See Nottingham health profile (NHP) NK-1 antagonists aprepitant antipruritic effects, neurokinin receptor antagonist, cutaneous transmission of itch, NK1R in the skin, substance P (SP) in pruritus, in the skin, tachykinin family, NNOS. See Neuronal nitric oxide synthase (nnos) Nociceptors capsaicin, 46 CMi, 43 conditional genetic knockout techniques, 49 mechano-heat-responsive, 41 polymodal, 41, 42 Nonsteroidal anti-inflammatory drugs (NSAIDs), Noradrenaline reuptake inhibitors, 214 Norbinaltorphimine (norbni) chlorpheniramine/u-50,488, GNTI, 301 ICR mice, 301 icv and ddy mice, 302 JDTic, 301 pharmacophores, 300 prototype kappa receptor, 300 Nottingham health profile (NHP), 28 Nppb. See Natriuretic polypeptide b (Nppb) NT4. See Neurotrophin 4 (NT4) O Oatmeal moisturisers, 341 Oncostatin M (OSM), Opioid receptor, 201 kappa opioid receptor agonists, mu opioid receptor antagonists, partial agonists, Opioids, 350

8 378 Index P Pain antiepileptic drugs, 349 capsaicin, capsaicin-induced, 44, 49 human skin, 46 PARs, specificity, 40 PAMPs. See Pathogen-associated molecular patterns (PAMPs) PAR 2. See Proteinase-activated receptor 2 (PAR 2) Paraneoplastic pruritus, 248 PARs. See Protease-activated receptors (PARs) Pathogen-associated molecular patterns (PAMPs), 137 Pattern theory, 46, 50 PET. See Positron emission tomography (PET) Pharmacological antagonism by non-opioid ligands histamine H1 receptor antagonists, 328 nonsteroidal anti-inflammatory drugs (NSAIDs), 328 serotonin 5-HT3 receptor antagonists, 325, by opioid-related ligands kappa opioid receptor agonists, mu opioid receptor antagonists, opioid receptor partial agonists, Pharmacological significance antipruritic agents, 208, 209 chronic pruritic diseases, 208 itching and scratching, 208, 209 Phospholipase C (PLC), 225 Phototherapy, 353 Positron emission tomography (PET), 58 Precuneus, 60, 62, 63, 66, 224 Primary afferents in primates axon reflex flare, 42 C-fibers, 41, 44 CNS, 42 Aδ fibers, 44 histamine, 41 human skin nerves, 42 mechanosensitive and mechano-insensitive nociceptors, 41 specimen, 43 structural markers, Primary sensory neurons, 141, 144 Prostanoid inhibitors, 345 Protease-activated receptors (PARs), 97 alloknesis elicited by pruritogens, 229 chronic itch, and itch, itch sensitization, mediated itch, and pain, and scratching alloknesis elicited by pruritogens, 229 classification, 7 8 histamine-evoked, 225 and itch sensation (see Itch(ing)) in mice, 221 PAR-1 agonist-evoked, 223, 225 PAR-2 knock-out mice, 221 pruritic diseases, 208, 209 pruritogen-evoked, 227 SLIGRL-evoked, 225 in Sprague Dawley rats, 221 terminology, 2 4 touch-evoked, 227 trypsin-evoked, 225 Proteases and receptors, 97 Proteinase-activated receptor 2 (PAR 2), 44 Pruriceptive itch, 94 Pruriceptive sensory fibers C-afferent axons, histamine-sensitive/insensitive sensory neurons, 92 Mrgprs family, 92 Pruriceptive signals, transmission excitatory neurotransmission, spinal cord expression of Grp, natriuretic peptide receptor A (Npr1), substance P, 157 inhibitory transmission, spinal cord dynorphin, kappa-opioid receptor agonist, 158 somatostatin receptor 2 (Sstr2), 158 voltage-gated sodium channel Nav1.8, from primary itch-receptor neurons excitatory transmitter glutamate, 152 gastrin-releasing peptide receptor (Grpr), 153 natriuretic polypeptide b (Nppb), neurotransmitters and receptors, 154 potential glutamate co-transmitter, Pruriceptors, 181 Prurigo

9 Index 379 dermatoses, 3 distinct condition, 8 and pruritus, 7 Prurigo nodularis (PN), 244 Pruritic sensory neurons, 152, 155 Pruritic TRP channels canonical (TRPC), 100 Drosophila channels, 100 heteromultimerization, 101 mammalian channels, subfamilies, thermotrps, TRPA1, TRPM4, 101, 112 TRPM8, TRPM6 and TRPM7, 112 TRPV2, TRPV3 and TRPV4, vanilloid (capsaicin) receptor TRPV1, Pruritogens, 221, 227, 229 Pruritus acute (see Acute pruritus) allergic pruritus dog model flea, house dust mite, cholestatic or uremic, 324, 327 chronic (see Chronic pruritus) definition, 90, 141 gastrin-releasing peptide (GRP), 142 histamine, 142 H 4 R, 271 H 1 R antihistamines, IL-2, 172 IL-4, 170 IL-6, 171 IL-31, incidence and prevalence general population, 17 IFSI, 24 patients, 21 predictors, itch, pruritus, 17, 19 induction by single substances, intensity theory of itch, itching, 3 labeled-line theory of itch (specificity theory), 91 mediators histamine, inflammatory, neuropeptides, neurotrophins, 98 proteases and receptors, 97 NSAIDs, 328 opioids, side effects, 317 and prurigo, 7 role of SP, scabies, 9 senilis, 8 skin diseases, 7 skin itch, 8 SP, 241, subthreshold pain, 90 surgical treatment, 11 systemic treatments, (see also Systemic therapies) topical treatments, (see also Topical therapies) vulvae and ani, 10, 11 Pruritus epidemiology. See also QoL, impact of pruritus CDLQI, 25 chronic pruritus, general population, classification and definition, cutaneous drug reaction, 23 dermatologic disease, 20 DLQI, 25 estimation, 24 general population, hematologic disease, 22 hepatic disease, neoplasms, 22 other diseases, predictors, itch, psychiatric disease, 20 renal disease, 21 scratching, 19 Skindex, 25 systemic diseases, Psoriasis, 20, 25, 27, 28, 114, 243, 244, 268, 275 Psychogenic itch, 95 Q QoL. See Quality of Life (QoL) QoL, impact of pruritus dermatoses atopic dermatitis, 27 chronic urticaria, 28 psoriasis, vitiligo, 29 extracutaneous disease chemical exposure, 30 chronic venous insufficiency, 29 30

10 380 Index QoL (cont.) ESRD, 30 systemic sclerosis, 29 instruments, population studies, 26 predictors, Quality of Life (QoL), 15 31, 82, 146, 208, 239, 339, 351 R Rat behavior, 294 bombesin test, 298 H 4 R mrna expression, 273 identification of MOP1D, 318 intrathecal administration of morphine, 316, 318 MrgprC receptors, 75 myeloperoxidase, 105 paw formalin test, 298 Receptors gastrin-releasing peptide receptor (Grpr), 153, IL-2 receptor (IL-2R), kappa-opioid receptor (Opkr1), 158 mas-related G protein-coupled receptor (Mrgpr), 168 natriuretic peptide receptor A (Npr1), OSM receptor (OSMR), 168 somatostatin receptor 2 (Sstr2), 158 TNF receptor 1 (TNFR1), TSLP receptor (TSLPR), 170 S Scabies, 94 bladder, 5 blood-letting, 7 dermatology, 5 diagnoses, 12 itching, 6 pustules, 4 ulcers, 7 SCORAD (SCORing Atopic Dermatitis), 245 Scratching classification, 7 8 kappa receptors for (see also Compound 48/80) antinociceptive-50, 296 arylacetamide, 296 asimadoline, 296 dysphoria and psychotomimesis, 296 EKC, 295 GR 94839, 296 GRP, 295 ICI 204,448, 296 icv bombesin-induced, 295 ketocyclazocine, 293 mu (μ) opioid analgesics, 293 nalorphine/cyclazocine, 294 naloxone, 294 N-(2-aminocyclohexyl)arylacetamide, 294 norbni, 302 opioid pharmacology, 294 Sprague Dawley rats, 302 Swiss Webster mice, 301 U-50,488, 294 zyklophin, 304 and PARS (see Protease-activated receptors (PARs)) terminology, 2 4 Sensation, itching counterirritants, distraction, 210 Sensory neuron-specific receptors (SNSRs), 74 SEPSCs. See Spontaneous excitatory postsynaptic currents (sepscs) Ser-Leu-Ile-Gly-Arg-Leu (SLIGRL), 78, 79, 144, 184, 192, , 229 Ser-Leu-Ile-Gly-Arg-Leu-NH 2 (SLIGRL), 222, 224, 225, 227 Serotonin 5-HT3 receptor antagonists effects of ondansetron, neuraxial opioid-induced pruritus, Single-neuron recordings, 41 Somatostatin receptor 2 (Sstr2), 158 Specificity theory capsaicin, 46 CNS, 46 GRPR, 47 nociceptors, 46 pain, 40 pattern theory, 46 Spinal itch processing GRPR, 93 histamine neurons, MORD1, Nppb, 93 Spinothalamic tract (STT), 320 Spontaneous excitatory postsynaptic currents (sepscs), 145

11 Index 381 Substance P and NK1R in skin in CNS and peripheral tissues, 241 CRHR-1, 243 CRPS, 243 cutaneous thermal hyperemia, 243 efferent function, 242 functions, induction of neurogenic inflammation, keratinocytes and fibroblasts, physiological and pathophysiological processes, 241 stress response, 243 in pruritus AD, cholestatic pruritus, prurigo nodularis (PN), 244 psoriasis, 244 Systemic pharmacological agents α-adrenoceptor agonists, gabapentin/pregabalin, 214 noradrenaline reuptake inhibitors, 214 tramadol inhibits noradrenaline, 214 Systemic therapies glucocorticosteroids, 348 systemic antihistamines, 345 T Tachykinins, T-cell lymphoma, 20 TCIs. See Topical calcineurin inhibitors (TCIs) Thymic stromal lymphopoietin (TSLP), 170 keratinocytes, 183, 184, 186 mouse model, 110 TLRs. See Toll-like receptors (TLRs) TNF Alpha, Toll/IL-1R (TIR) homology domains, 140 Toll-like receptors (TLRs), 104 central glial cells, sepscs, 145 clinical significance, 146 DAMPs, 137 in Drosophila melanogaster, 137 endotoxins (lipopolysaccharide), 137 itch or pruritus, ligands, PAMPs, 137 peripheral epidermal keratinocytes, 142 nerve growth factor (NGF), spinal cord and DRG, 144 TLR3 and TLR7, signaling pathways, structure, 138 Tonic inhibition, 214 Topical calcineurin inhibitors (TCIs), Topical therapies anaesthetics, 342 antihistamines, 344 calamine, 342 cannabinoids, 344 capsaicin, emollients, glucocorticoids, 343 ion channel blockers, 345 menthol, 341 oatmeal moisturisers, 341 prostanoid inhibitors, 345 TCIs, Transient receptor potential (TRP) channels canonical, for itch relief chronic itch, 115 pharmacological intervention, TRPV1 antagonists, pruriceptive system, neural organization higher itch centers, 94 pruriceptive sensory fibers, spinal itch processing, pruritic (see Pruritic TRP channels) pruritus, types and mediators, Transmission, itching α1-adrenoceptors, α2-adrenoceptors, 213 descending noradrenergic system, TRP. See Transient receptor potential (TRP) channels TRPA1 chloroquine, histamine-independent itch, 110 hydrogen peroxide-induced itch, 110 in lung fibroblasts, proinflammatory interleukins, 111 SP release, 111 TRPC channels, TRP channelopathies, 101 TRPM4, 112 TRPM6, 112 TRPM7, 112 TRPM8, TRPV1, 96, 240

12 382 Index TRPV1 (cont.) cloning, 106 clotrimazole, 107 endocannabinoid anandamide, endogenous substances, histamine activation, 103 in non-neuronal cells, 105 PAR-2-coupled pruriceptive signaling, Pirt, phosphoinositide-binding protein, 104 polymodal nociceptor, 102 pruriceptive itch, tacrolimus, 107 TLRs, 104 VGLUT2, TRPV2, TRPV3, TRPV4, 109 TSLP. See Thymic stromal lymphopoietin (TSLP) U Urticaria clinical data, 263, 264 H 1 R, , 275 intradermal histamine injection, 258 mosquito bites, 265 V Varicose veins, 10 Ventral posterior inferior (VPI), 59 Ventral posterior lateral (VPL), 59 Vesicular glutamate transporter (VGLUT3), 42, 45, 193 Vesicular glutamate transporter type 2 (VGLUT2), VGLUT2. See Vesicular glutamate transporter type 2 (VGLUT2) VGLUT3. See Vesicular glutamate transporter (VGLUT3) VPI. See Ventral posterior inferior (VPI) VPL. See Ventral posterior lateral (VPL) Z Zyklophin C57BL/6 J controls, 304 cyclic peptide, Swiss Webster mice, 304