ライフサイエンスコーパス: itch

1 ild itch), 4-7 (moderate itch), 8-10 (severe itch).

2 nd induced pathophysiological responses (ie, itching).

3 nities for their interaction with the PRR of Itch.

4 /receptors involved in acidic citrate-evoked itch.

5 uropathy and 167 JHS/EDS-HT patients without itch.

6 e homolog MrgprC11, implicated previously in itch.

7 he WW domain of the host E3 ubiquitin ligase ITCH.

8 bfamily A, member 1) have been implicated in itch.

9 ESCRT adaptor Alix, and the ubiquitin ligase Itch.

10 e 1 painless diabetic neuropathy and chronic itch.

11 tion by the co-recruited E3 ubiquitin ligase ITCH.

12 TRPV4 is a key mediator of serotonin-induced itch.

13 tivity to minimal stimuli inducing sustained itch.

14 inds to UbcH7, whereas the PY motif binds to Itch.

15 e was applied to the right forearm to induce itch.

16 eptor HTR7 as a key mediator of serotonergic itch.

17 ide Y::Cre (NPY::Cre) act to gate mechanical itch.

18 nce, Ndfip1 acts as an adaptor for UbcH7 and Itch.

19 an induce a form of itch known as mechanical itch.

20 f ubiquitin-conjugating enzyme (E2) UbcH7 to Itch.

21 ay that gates the transmission of mechanical itch.

22 ectors all have dramatic effects on pain and itch.

23 ing our understanding of the neural basis of itch.

24 s dispensable for beta-alanine-induced acute itch.

25 sensory neurons rather than NK-1R to induce itch.

26 somatosensory modalities of touch, pain, and itch.

27 ited the activity of the ubiquitin E3 ligase Itch.

28 were dryness, redness, burning sensation and itching.

29 An alternative scoring is based on itching.

30 SI (0.56 and 0.50), BSA (0.52 and 0.45), NRS-itch (0.60 and 0.53), POEM (0.50 and 0.48), and DLQI (0.

31 reement (kappa = 0.69) was as follows: 0 (no itch), 1-3 (mild itch), 4-7 (moderate itch), 8-10 (sever

32 motor skills, 48.7 vs 53.0 [P = .002]; pain/itching, 15.8 vs 33.5 [P < .001]; and worry/concern, 31.

33 ity of scratching as an objective measure of itch (4-point ordinal scale ranging from 0 [not present]

34 0.69) was as follows: 0 (no itch), 1-3 (mild itch), 4-7 (moderate itch), 8-10 (severe itch).

35 Rash (84 reports), itching (46 reports), and vomiting (30 reports) were the

36 (-17.1/-9.8/-3.2), BSA (-46%/-15%/-4%), NRS-itch (-5/-2/0), POEM (-5/-2/0), and DLQI (-8/-6/-1) than

37 0 (no itch), 1-3 (mild itch), 4-7 (moderate itch), 8-10 (severe itch).

38 r-TRP in skin keratinocytes in histaminergic itch, a novel basic concept with translational-medical r

39 nity, the itchy E3 ubiquitin protein ligase (ITCH)-A20 ubiquitin-editing complex inhibits receptor-in

40 Unlike beta-endorphin, which produces itch and attenuates inflammatory pain, GRP only elicits

41 Long persistence of cowhage-induced itch and diminished histamine-induced flare in nonlesion

42 ized spinal circuit for mechanically-induced itch and elucidated a mechanism that keeps it in check.

43 They did not complain of itch and had had symptoms for an average of 9 months.

44 y activated the reward system in the chronic itch and healthy groups, confirming that this reward sys

45 These measures included Skindex-29, current itch and hives scores, total leukocyte histamine content

46 ntributor to the pathogenesis of neuropathic itch and identifying a new candidate therapeutic target.

47 -derived GABA are antipruritic against acute itch and in a transgenic mouse model of atopic dermatiti

48 Although both persistent itch and inflammation are commonly associated with aller

49 Our results demonstrate that persistent itch and inflammation are mediated by distinct cellular

50 the pathophysiology and treatment of chronic itch and inflammation in ACD patients.

51 se by HOCl, leading to significantly reduced itch and inflammation in vivo.

52 tinct roles of TRPA1 and TRPV1 in regulating itch and inflammation may provide new insights into the

53 Substance P (SP) is linked to itch and inflammation through activation of receptors on

54 athophysiological conditions including pain, itch and inflammation.

55 y an important role in nociceptive, thermal, itch and light touch sensations.

56 lved in many sensory disorders such as pain, itch and neuropathy.

57 Itch and pain are closely related but are distinct sensa

58 Slo2.2, but not Slo2.1, results in enhanced itch and pain responses.

59 ct functions of neuropeptides for modulating itch and pain.

60 ghlight a role for HTR7 in acute and chronic itch and suggest that HTR7 antagonists may be useful for

61 cuss recent advances in our understanding of itch and the molecular players that mediate this sensory

62 model in which Grp(+) neurons transmit both itch and weak pain signals; however, upon strong painful

63 gastrointestinal symptoms), and reduction in itching and whealing after standardized skin provocation

64 Both Itch(-/-) and Ndfip1(-/-) mice exhibited severe airway i

65 pendent model of histamine-induced pruritus (itch) and additionally in a capsaicin-induced nociceptio

66 id reactions, neurogenic inflammation, pain, itch, and chronic inflammatory diseases, such as urticar

67 ctivity leading to skin barrier dysfunction, itch, and dermatitis via the PAR2-TSLP pathway.Journal o

68 ctivity leading to skin barrier dysfunction, itch, and dermatitis via the protease-activated receptor

69 ted TrpC3 null mice for beta-alanine induced itch, and found that these mice exhibit normal responses

70 ry pathways are important mediators of pain, itch, and neurogenic inflammation.

71 disability weight, measuring disfigurement, itch, and pain caused by scabies, to produce years lived

72 to the development of allergy, autoimmunity, itch, and pain.

73 Injection site pain, itching, and erythema (mostly mild) were the only solici

74 sponded to diverse ligands known to activate itch- and pain-sensing neurons.

75 emotional behavior, family functioning, pain/itching, appearance, satisfaction with care, and worry/c

76 Pain and itch are unpleasant sensations accompanying many microbi

77 e the clinical symptoms of wheal, flare, and itch arise from within the patient.

78 her TRPV4 in skin keratinocytes functions in itch, as a particular form of "forefront" signaling in n

79 We show that Itch associates with Alix and BFRF1 and is required for

80 f 1 point or greater had significantly lower itch based on numeric rating scale in the past 3 days (W

81 l report the failure of observing contagious itch behavior using mice injected with histamine as the

82 ns to identify transcripts co-regulated with itch behavior.

83 e ion channel TRPA1, which in turn triggered itch behaviors.

84 we report that this phosphorylation impedes ITCH binding to its cognate E2 ubiquitin ligase, UbcH7.

85 neous nerves and an accompanying increase in itching, both of which were abolished in the absence of

86 Mechanistically, Itch bound to the transcription factor ROR-gammat and ta

87 incidence of local side effects (redness and itching) but a similar incidence of systemic side effect

88 rain activity likely supports nocebo-induced itch, but is currently unknown.

89 histamine, reduced the intensity of cowhage itch by approximately 35%, and did not affect heat pain

90 c circuit were involved in the inhibition of itch by butorphanol and could represent potential target

91 The suppression of histamine itch by butorphanol was paralleled by the activation of

92 istically that progesterone sulfates mediate itch by evoking a Tgr5-dependent scratch response in mic

93 Like closely related ligases, Itch can interact with proteins containing a PPXY motif

94 ease the HECT, allowing trans-thiolation and Itch catalytic activity.

95 nto the pathophysiology of acute and chronic itch, chronic itch remains an often intractable conditio

96 he view that pruritogens engage spinal cord "itch" circuits via excitatory superficial dorsal horn in

97 A key question in our understanding of itch coding mechanisms is whether itch is relayed by ded

98 g has mounted, studies promoting alternative itch-coding strategies have emerged, complicating our un

99 that gives rise to the perceptions of pain, itch, cold and heat are initially integrated in the supe

100 r potency in blocking non-histamine-mediated itch compared with Sal A, and this difference is not see

101 seful for treating a variety of pathological itch conditions.

102 roteins identifies additional populations of itch-dedicated sensory neurons.

103 Itch deficiency in the TH17 subset of helper T cells, in

104 role in the regulation of inflammation, and Itch deficiency leads to severe airway inflammation.

105 Here, we show that itch deficits in mice lacking NMB or GRP are non-redunda

106 functioned by hijacking Notch receptors from Itch-dependent lysosomal degradation.

107 ically used for chronic hepatic diseases and itching dermatitis, modulates the pathological processes

108 re, we report that the ubiquitin (Ub) ligase Itch directly interacts with and monoubiquitinates SMN.

109 RS), primary biliary cholangitis-40 (PBC-40) itch domain score and 5-D itch scale, changes in serum t

110 RS (-23%, 95% CI -45 to -1; p=0.037), PBC-40 itch domain, (-14%, -26 to -1; p=0.034), and 5-D itch sc

111 Itch duration was evaluated following histamine iontopho

112 We discuss whether pain and/or itch during infection is beneficial or harmful to host a

113 For example, our results suggest that itching during inflammatory skin diseases such as atopic

114 rimary biliary cholangitis develop pruritus (itch) during the course of their disease.

115 n of NOTCH2 into ARMMs is facilitated by the ITCH E3 ligase and the metalloprotease ADAM10, both of w

116 receptor, and Janus kinase) or specifically itching (eg, NK1R inhibitors) are also being studied.

117 particular, we demonstrate causal links for itch-eliciting effects by beta-endorphin-MOP receptor an

118 nth history of epigastric pain and jaundice, itching, flushing, cough and wheezing.

119 The persistence of cowhage-induced itch for at least 30 min and a histamine-induced flare o

120 mple, standardized, objective assessments of itch for clinical trials and practice.

121 n the quality, intensity, and persistence of itch, for wheal diameter, volume, and flare size and int

122 uded additional VAS items (burning/stinging, itching, foreign body sensation, eye discomfort, photoph

123 ts provide new mechanistic insights into how Itch function is regulated during inflammatory signaling

124 Y motifs are required for Ndfip1 to activate Itch, functionally distinguishing Ndfips from single PY-

125 as atopic dermatitis is linked to a distinct itch-generating type.

126 converts the keratinocyte into an organismal itch-generator cell.

127 atisfactory neurobiological understanding of itch has proved difficult to reach.

128 cratching severity for patients experiencing itch improvement of 4 points or greater in the past 3 da

129 he well-established histamine model of acute itch in demonstrator mice.

130 A5 rare variants co-segregating with chronic itch in eight affected members and absent in non-affecte

131 s acid (HOCl) formulations lead to relief of itch in human patients with atopic dermatitis; however,

132 PAR-4 activation by AYP causes pruriceptive itch in mice via a TRPV1/TRPA1-dependent mechanism.

133 on channel, plays an important role in acute itch in mice.

134 ave identified a previously unknown role for Itch in regulating IL-17-mediated colonic inflammation a

135 amine are pruritogens commonly used to study itch in the mouse.

136 0.336, P < 0.0001), numeric rating scale of itch in the past 24 hours (tau = 0.266, P = 0.0010) and

137 are an integral part of neural circuits for itch in the spinal cord.

138 Later, she felt itching in her mouth.

139 After that she felt discomfort and itching in her oral cavity.

140 receptors; however, in many forms of chronic itch, including alloknesis, this gating mechanism is los

141 Itch induced by acidic citrate, but not alpha-methyl-5-h

142 ptor (NK-1R), we sought to determine whether itch induced by SP can also be mediated by Mrgprs.

143 Butorphanol suppressed the itch induced experimentally with histamine, reduced the

144 functions as the molecular receptor for the itch-inducing chemical beta-alanine.

145 Moreover, we report an itch-inducing molecule, cyclic phosphatidic acid, that a

146 opose that NMB and GRP may transmit discrete itch information and NMBR neurons are an integral part o

147 y and sufficient for transmitting contagious itch information in the SCN.

148 OP receptor and GRP-BB2 receptor systems and itch-inhibiting effects by the dynorphin A-KOP receptor

149 or deleting these residues facilitated GLI1-ITCH interaction and decreased the protective effect of

150 Chronic, persistent itch is a devastating symptom that causes much suffering

151 Itch is also implicated in other biological contexts suc

152 ITCH is an E3 ubiquitin ligase that has been shown to po

153 Further, we demonstrate that chronic itch is dependent on neuronal IL-4Ralpha and JAK1 signal

154 Among major contributors to chronic itch is dysfunction of spinal cord gamma aminobutyric ac

155 ery, numerous studies have demonstrated that Itch is involved in the control of many aspects of immun

156 These results indicate that 5-HT-induced itch is linked to TRPV4.

157 ought to be carried by pain-sensing neurons, itch is now believed to be capable of being transmitted

158 Although once considered a subtype of pain, itch is now recognized as a unique sense, with its own d

159 ITCH is phosphorylated and thereby inhibited by inhibito

160 tanding of itch coding mechanisms is whether itch is relayed by dedicated molecular and neuronal path

161 Itch is relayed to higher centers by projection neurons

162 Itch is thought to represent the peculiar response to st

163 Socially contagious itch is ubiquitous in human society, but whether it exis

164 ides closely related to GRP, but its role in itch is unclear.

165 ceptor potential vanilloid type-4 (TRPV4) in itch is unknown.

166 Pruritus (itch) is a symptom commonly experienced by patients with

167 "catastrophizing cognitions" with respect to itching (Juckreiz-Kognitions-Fragebogen questionnaire),

168 RAD (kappa = 0.47), EASI (kappa = 0.37), NRS-itch (kappa = 0.49), POEM (kappa = 0.37), and DLQI (kapp

169 imulation of hairy skin can induce a form of itch known as mechanical itch.

170 ce, supporting the hypothesis that CQ evokes itch largely via stimulation of MrgprA3 receptors.

171 Intriguingly, the loss of ITCH lead to a reduction in circulating cholesterol leve

172 ed GLI1 binding with the E3 ubiquitin ligase-ITCH, leading to decreased K48-linked ubiquitination/deg

173 ound that deficiency in the ubiquitin ligase Itch led to spontaneous colitis and increased susceptibi

174 biquitin ligases, BFRF1 preferentially binds Itch ligase.

175 question of whether acid (protons) can evoke itch like other algogens by spatial contrast activation

176 ITCH, like Nedd4, is a member of the HECT class of E3 ub

177 tus axis identifies a therapeutic target for itch management in ICP.

178 Thus, modulation of ITCH may provide a target for the treatment of hyperchol

179 se severity RR 2.85 (95% CI 1.02, 7.96); and itch mean difference -4.20 on a 10-point scale (95% CI -

180 Conversely, ITCH-mediated downregulation of WBP2 inhibited TCF/beta-

181 icate that CLP causes bone loss by enhancing Itch-mediated osteoclastogenesis, which was prevented by

182 Recent studies demonstrate that pain- and itch-mediating somatosensory neurons are able to directl

183 reduced spontaneous colonic inflammation in Itch(-/-) mice.

184 ApoE-/-ITCH-/- mice fed a western diet for 12 weeks showed incr

185 omote OC formation from bone marrow cells of Itch-/- mice in vitro nor induce bone loss in Itch-/- mi

186 tch-/- mice in vitro nor induce bone loss in Itch-/- mice.

187 The E3 Ubiquitin Ligase ITCH modulates lipid metabolism impacting on atheroscler

188 Thus, our studies discover that Itch monoubiquitinates SMN and monoubiquitination of SMN

189 ing (n = 10; 23%), photophobia (n = 6; 14%), itching (n = 4; 9%), swelling (n = 2; 5%), and infection

190 ermittent exposure to seasonal pollen causes itching, nasal congestion, and repeated sneezing, with p

191 ted CQ-induced action potential discharge at itch nerve terminals and bouts of scratching by about 50

192 (or other GPCRs) leads to activation of the itch nerve terminals in the skin, but previous studies h

193 tamine-induced action potential discharge in itch nerve terminals.

194 annels such as TMEM16a in GPCR-activation of itch nerve terminals.

195 r and molecular mechanisms involved in pain, itch, nerve injury and regeneration.

196 KEY POINTS: Chloroquine (CQ) stimulates itch nerves and causes intense scratching in mice by act

197 on of the putative primary afferent-derived "itch" neurotransmitter, gastrin-releasing peptide (GRP).

198 ifitegrast-treated participants at day 42 in itching (nominal P = 0.0318), foreign body sensation (no

199 d be considered in the management of chronic itch, notably atopic dermatitis.

200 Yu et al state that contagious itch occurs in mice based on imitative scratching in nor

201 Participants rated their itch on the ItchyQuant, on a traditional 11-point NRS, a

202 thout an increase in sensitivity to chemical itch or pain.

203 and distinguish between stimuli that provoke itch or pain.

204 Positive criteria are based on itching or quoted according to a composite score.

205 have non-specific symptoms such as lethargy, itch, or loss of appetite.

206 gnificant difference in disability, fatigue, itching, or patient or clinician global disease severity

207 dy outcomes: coping behavior with respect to itching (P < .001), quality of life assessed by using th

208 owever, there was a dose-related increase in itching, pain, edema, and staining of the anogenital ski

209 effective available therapy, mainly because itch pathophysiology is not completely elucidated.

210 Determining inflammation and itch pathway activation in patients with atopic dermatit

211 nduced flares (P < 0.01) and markedly longer itch persistence after provocation with cowhage (P < 0.0

212 ow that genetic UbcH7 deficiency phenocopies ITCH phosphorylation in regulating RIPK2 ubiquitination.

213 The ubiquitin-ligating enzyme (E3) Itch plays a crucial role in the regulation of inflammat

214 The ligase Itch plays major roles in signaling pathways by inducing

215 antly higher oSCORAD, SCORAD, EASI, BSA, NRS-itch, POEM, and DLQI (P < .0001 for all).

216 In addition to these WW domains, Itch possesses a proline-rich region (PRR) that has been

217 During the process, a ubiquitin ligase, Itch, preferably associates with BFRF1 and is required f

218 ive direct synaptic input from both pain and itch primary sensory neurons.

219 insula, and putamen, areas activated during itch processing.

220 Many signaling pathways are regulated by Itch-promoted ubiquitylation of diverse target proteins.

221 These structures depict the position of Itch PRR engaged in a 1:2 protein complex with beta-PIX

222 mass spectrometry analysis, we show that the Itch PRR preferentially forms complexes with endophilins

223 esults reveal the binding preferences of the Itch PRR toward its most common SH3 domain-containing pa

224 the wide range of binding properties of the Itch PRR.

225 TRPV1 and TRPA1 function downstream of many itch receptors, where they mediate inward current to tri

226 ), were intradermally injected into mice and itch-related scratching behavior was assessed.

227 To confirm itch relief and reduction of lesions in a mouse model of

228 nt with gabapentinoids provided satisfactory itch relief in the patients carrying the mutations.

229 chronic itch, suggesting a new strategy for itch relief.

230 ammatory pathways promote sensations such as itch remain poorly understood.

231 hysiology of acute and chronic itch, chronic itch remains an often intractable condition.

232 , inhibits TRPV1 activity, and also pain and itch responses in mice by interacting with the vanilloid

233 ed rarely seen, simultaneous robust pain and itch responses that were intensity dependent.

234 n and concomitant increases in site-specific itch responses.

235 ory nerve substance P and, in turn, increase itching responses.

236 s that fail to interact with either UbcH7 or Itch, restored the defect in Tak1 ubiquitination and inh

237 1, a co-activator of the E3 ubiquitin ligase Itch, restricts the frequency and pathogenicity of Th17

238 tion and degradation, and loss of TAX1BP1 or Itch results in increased MAVS protein expression.

239 domain, (-14%, -26 to -1; p=0.034), and 5-D itch scale (-20%, -34 to -7; p=0.0045).

240 ys (Wilcoxon rank sum test, P = 0.0175), 5-D itch scale (P = 0.0146), and Patient-Oriented Eczema Mea

241 ngitis-40 (PBC-40) itch domain score and 5-D itch scale, changes in serum total bile acids and 7 alph

242 of severe HTS (VSS>7) was 49%, and the mean itch score was 3.9.

243 R SNP genotype was associated with increased itch score.

244 dependently elicit the same degree of robust itch scratching, which can be inhibited by mu-opioid pep

245 Scratching significantly attenuated the itch sensation (P<0.001) and evoked an associated pleasu

246 This itch sensation is normally suppressed by inputs from mec

247 h a focus on the role of Mrgprs in mediating itch sensation.

248 or exploring the mechanism underlying spinal itch sensation.

249 he molecules, cells, and circuits underlying itch sensation.

250 research tool to isolate and study cutaneous itch-sensing nerves in human skin.

251 and six principal types of thermosensitive, itch sensitive, type C low-threshold mechanosensitive an

252 for association with severe HTS (VSS>7) and itch severity (0-10) was based on multivariate regressio

253 f progesterone sulfates were associated with itch severity and, in combination with autotaxin, distin

254 an be added to the existing armamentarium of itch severity scales.

255 yQuant is a clinically meaningful measure of itch severity, demonstrating face and concurrent validit

256 d self-report numeric rating scale (NRS) for itch severity.

257 s important to accurately assess and measure itch severity.

258 Our findings show how WBP2/ITCH signaling functions to link the intricate Wnt and H

259 imary afferent neurotransmitter that conveys itch signals to the spinal cord.

260 Accordingly, ITCH silencing could elevate WBP2 levels.

261 s characterized by typical symptoms of nasal itching, sneezing, watery discharge and congestion.

262 al lymphopoietin, IL-4, IL-5, IL-13, and the itch-specific cytokine IL-31 and their receptors) or TH2

263 coupled receptor (Mrgpr) family demarcate an itch-specific labeled line in the peripheral nervous sys

264 d that gastrin-releasing peptide (GRP) is an itch-specific neurotransmitter.

265 h without affecting responses to noxious and itch stimuli.

266 ion between COL6A5 gene and familiar chronic itch, suggesting a new contributor to the pathogenesis o

267 of this circuit could contribute to chronic itch, suggesting a new strategy for itch relief.

268 Humans and mice detect pain, itch, temperature, pressure, stretch and limb position v

269 To streamline the contagious itch test, the screen paradigm is highly recommended.

270 of scratching bouts required for contagious itch test.

271 Nocebo saline produced greater itch than open saline control (P < 0.01).

272 erve that patients with recalcitrant chronic itch that failed other immunosuppressive therapies marke

273 some patients suffer from chronic idiopathic itch that is frequently ascribed to psychological distre

274 autotaxin, distinguished pregnant women with itch that would subsequently develop ICP from pruritus g

275 a novel and functional EBOV VP40 interactor, ITCH, that regulates VP40-mediated egress.

276 Itch, the irritation we feel and the relief that comes f

277 uncovers an unanticipated role for TRPV4 in itch, thereby identifying a novel therapeutic target.

278 s are not GABA pumps, but alleviate pain and itch through synaptic release of GABA.

279 TAX1BP1 recruits the E3 ligase Itch to MAVS to trigger its ubiquitination and degradati

280 TAX1BP1 functions as an adaptor molecule for Itch to target MAVS during RNA virus infection and thus

281 l nervous system are important modulators of itch transmission.

282 In addition, acute itch triggered by serotonin or a selective serotonin reu

283 ng CRISPR-Cas9 genetic knockout to mimic the ITCH-UbcH7-inhibited state, we further show that genetic

284 Therefore, our data indicate that Itch, ubiquitin, and Alix control the BFRF1-mediated mod

285 Our data demonstrate that Itch, ubiquitin, and Alix control the BFRF1-mediated mod

286 such as anaphylaxis, food allergy, rhinitis, itch, urticaria, atopic dermatitis, and asthma.

287 Coding of itch versus pain has been heatedly debated for decades.

288 rp(+) neurons increased pain responses while itch was decreased.

289 hether or not they play an analogous role in itch was previously unknown.

290 urons (pruriceptive fibers), and AYP-induced itch was reduced by the selective GRP receptor antagonis

291 Importantly, AYP-induced itch was reduced by treatment with either the selective

292 Wnt signaling upregulated WBP2 by disrupting ITCH-WBP2 interactions via EGFR-mediated tyrosine phosph

293 vements in quality of life, symptom control (itching, wheals and flares, flushing, tachycardia, and h

294 WBP2 levels were controlled by the E3 ligase ITCH, which bound and target WBP2 for ubiquitin-dependen

295 We identified somatic mutations in ITCH, which impaired its ability to degrade WBP2 and to

296 EDS-HT), characterized by idiopathic chronic itch with predominantly proximal distribution.

297 related to understanding the neural basis of itch, with a focus on the role of Mrgprs in mediating it

298 tenuates inflammatory pain, GRP only elicits itch without affecting pain.

299 ively ablated or silenced develop mechanical itch without an increase in sensitivity to chemical itch

300 ns partially attenuated peripherally induced itch without compromising nociceptive processing.