ライフサイエンスコーパス: nociceptive

1 primary afferent neurons, many of which are nociceptive.

2 SP(-) afferent neurons are likely to be non-nociceptive.

3 me, are associated with exaggerated visceral nociceptive actions that may involve altered microbial s

4 ause glibenclamide did not affect their anti-nociceptive activities.

5 damaging stimuli, and this is accompanied by nociceptive activity generated in subcortical and cortic

6 old process that gates the transformation of nociceptive activity to conscious pain.

7 cending serotonergic fibres not only inhibit nociceptive activity, but also facilitate non-noxious ta

8 pressed Kalirin-7 is required for persistent nociceptive activity-dependent synaptic long-term potent

9 Here, high-speed videography during nociceptive Adelta fiber stimulation demonstrated engage

10 ted with two dissociable functional systems: nociceptive/affective aspects mediated by the NPS, and e

11 t serve to integrate both proprioceptive and nociceptive afferent information.

12 rs expressed on terminals of trigeminal (TG) nociceptive afferent neurons.

13 whether the peripheral or central anatomy of nociceptive afferent subtypes in different DCNs also var

14 s to determine whether inhibitory DREADDs in nociceptive afferents could be used to produce analgesia

15 RPV1) ion channel is mainly found in primary nociceptive afferents whose activity has been linked to

16 ization-evoked Ca(2+) transients in putative nociceptive afferents.

17 nic constriction injury bilaterally augments nociceptive amygdala (in the central nucleus of the amyg

18 self-regulation primarily influences primary nociceptive and affective processes or evaluative ones.

19 g/kg) produced a significant decrease in the nociceptive and inflammatory response to allyl isothiocy

20 Despite the convergence of nociceptive and mechanosensory inputs on common second-o

21 damide and tested for changes in response to nociceptive and non-nociceptive stimuli.

22 revent innocuous stimuli from activating the nociceptive and pruritic transmission pathways.

23 o evaluate PACAP plasticity and signaling in nociceptive and stress-related behaviors.

24 sensory experience during development alters nociceptive behavior and circuit physiology in Drosophil

25 Furthermore, while nociceptive behavior and cortical activity are normally

26 Newborn infants display strong nociceptive behavior in response to tissue damaging stim

27 a significant reduction in formalin-induced nociceptive behavior was observed.

28 Here we have simultaneously measured nociceptive behavior, brain activity, and levels of phys

29 that of the inflammation-induced changes in nociceptive behavior.

30 the heat-evoked action potential firing and nociceptive behavior.

31 ATP also induced robust biphasic spontaneous nociceptive behavior.

32 erotonergic cells were dispensable for acute nociceptive behaviors and for aversion induced by therma

33 ent with A438079 abolished all BzATP-induced nociceptive behaviors, while ROS scavengers dose-depende

34 inverse agonists potentiated TRPM3 mediated nociceptive behavioural responses.

35 NaV 1.7(Nav1.8) mice showed normal nociceptive behaviours in response to intracolonic appli

36 gest that selective optogenetic silencing of nociceptive bladder afferents may represent a potential

37 tation, we examined the relationship between nociceptive brain activity and spinal reflex withdrawal

38 oxious stimulus is a sensitive indication of nociceptive brain activity in term infants.

39 fants, we demonstrate that the maturation of nociceptive brain activity is concomitant with the refin

40 ng correlation between reflex withdrawal and nociceptive brain activity suggests that movement of the

41 While nociceptive brain activity, reflex withdrawal and facial

42 he frequency of action potentials relayed by nociceptive C fibers to the spinal cord.

43 te transient receptor potential ankyrin-1 on nociceptive C-fibers.

44 itic growth and maintenance of space-filling nociceptive C4da neurons, allowing them to innervate the

45 The nociceptive cation channel TRPV1 (transient receptor pot

46 n appears to be mediated by a persistent pro-nociceptive change in the gut micro-environment, that ha

47 tion, and instead appear to be driven by pro-nociceptive changes in the gut micro-environment.

48 on NGF and is mediated by the heat-sensitive nociceptive channel TRPV1.

49 which serve as a major output of the spinal nociceptive circuit and are essential for pain perceptio

50 athway-specific plasticity in the Drosophila nociceptive circuit is in part established through feedb

51 We reconstructed nociceptive circuits in a larva of each stage and found

52 s a long-term increase in the gain of spinal nociceptive circuits, and suggest that the prolonged con

53 these aromatase neurons are poised to engage nociceptive circuits, whether it is through local estrog

54 or the production of LTP within adult spinal nociceptive circuits.

55 ion in the spinal cord to genetically define nociceptive circuits.

56 llary system), EEG event-related potentials (nociceptive cortical activity), and facial expression (b

57 re we show that combining mechanosensory and nociceptive cues synergistically enhances the selection

58 w that the induction of hyperexcitability of nociceptive deep dorsal horn neurons by TNF-alpha largel

59 nt of TNF-alpha-induced hyperexcitability of nociceptive deep horsal horn neurons.

60 Hoxb8::cre expression in the development of nociceptive dorsal horn circuits critical for mechanical

61 for dorsal horn development, is expressed in nociceptive dorsal horn neurons and that its deletion re

62 ealthy volunteers, sensitized TRPV1 in mouse nociceptive dorsal root ganglion neurons via HRH1; this

63 y collect individual injured and non-injured nociceptive DRG neurons and to define their gene profili

64 ating a complete mismatch between peripheral nociceptive drive and perceived pain.

65 rtional to the amount of incoming peripheral nociceptive drive due to injury or inflammation in the a

66 However, the anti-nociceptive effect appears to be a consequence of the re

67 The mechanism involved in the anti-nociceptive effects of the ruthenium complexes suggested

68 d to the suggestion that H2 S exerts its pro-nociceptive effects via this channel, since Cav3.2 plays

69 These pro- and anti-nociceptive effects were blocked by co-injection of a TR

70 preclinical studies show both pro- and anti-nociceptive effects.

71 ifferent molecular weights produces opposing nociceptive effects.

72 hat endocannabinoids have both pro- and anti-nociceptive effects.

73 ccepting a reward at the cost of receiving a nociceptive electrocutaneous stimulus or rejecting both.

74 transmission due to the filtering effect at nociceptive fiber T-junctions.

75 ning molecular targets on this population of nociceptive fibers may prove useful for developing an im

76 tion could contribute to pain in the case of nociceptive fibers.

77 The nociceptive flexor withdrawal reflex has an august place

78 ticated molecular genetic dissection of cold nociceptive genes and circuits.

79 f distinct intrasegmental and intersegmental nociceptive heat and touch processing circuits in the sp

80 t fMRI activation patterns to tactile versus nociceptive heat stimulation of digits in lightly anesth

81 l networks for the processing of tactile and nociceptive heat stimuli in the cervical spinal cord of

82 cDH responded selectively to tactile versus nociceptive heat, respectively.

83 Nerve injury inducing nociceptive hypersensitivity also increases the expressi

84 nal plasticity underlying the progression of nociceptive hypersensitivity following neuropathic injur

85 el with heightened anxiety-like behavior and nociceptive hypersensitivity.

86 trigeminovascular system and transmission of nociceptive information and plays a key role in migraine

87 it is not known whether brain processing of nociceptive information differs in infants and adults.

88 l concomitant effects on the transmission of nociceptive information to the brain, as the degree to w

89 ing motor circuits and the ascending flow of nociceptive information to the brain, thus highlighting

90 re lamina I projection neurons, which convey nociceptive information to the brain.

91 ularly relating to the processing of A-fiber nociceptive information.

92 he processing and segregation of tactile and nociceptive information.

93 y that enables them to segregate tactile and nociceptive information.

94 esses contribute to pain beyond the level of nociceptive input and mediate psychological and behaviou

95 subjective changes in pain that result from nociceptive input and self-directed cognitive modulation

96 the dorsal horn synaptic network to amplify nociceptive input arising from muscle is predicted to fa

97 (SIIPS1)-that predicts pain above and beyond nociceptive input in four training data sets (Studies 1-

98 Despite receiving the identical nociceptive input, intensity ratings increased during th

99 owledge that pain is not a direct readout of nociceptive input, the neuronal processes underlying cog

100 hannels support the detection of noxious and nociceptive input.

101 inal pathways may modulate the processing of nociceptive inputs by SpVc, and regulate pain perception

102 nsory circuits of the dorsal horn (DH) where nociceptive inputs integrate for pain processing.

103 ofound, immediate and precise integration of nociceptive inputs with ongoing motor activities leading

104 DS can, by controlling the temporal relay of nociceptive inputs, influence the spinal summation of no

105 ific enhancement in the aversive response to nociceptive inputs.

106 al dorsal cutaneous nerves (DCNs) evokes the nociceptive intersegmental cutaneus trunci muscle (CTM)

107 d synaptic contacts on L-ITCc dendrites from nociceptive intralaminar thalamic nuclei.

108 potential ankyrin repeat 1 (TRPA1), a major nociceptive ion channel, but the underlying mechanisms a

109 se prevents Abeta-LTMR input from activating nociceptive lamina I neurons.

110 -Fos reveals the circuit extends dorsally to nociceptive lamina I projection neurons, and includes la

111 ntly reduced the ecto-AMPase activity in the nociceptive lamina in the brainstem.

112 ence of CD73 and ecto-AMPase activity in the nociceptive lamina of the trigeminal subnucleus caudalis

113 ical profile of CSNs revealed an increase of nociceptive-like phenotype among neurons from CCI animal

114 e significantly ameliorated inflammatory and nociceptive mediators both peripherally and centrally in

115 ults indicate that CD73 might participate in nociceptive modulation by affecting extracellular adenos

116 urons and their axonal fibers, including the nociceptive nerve fibers projecting into the brainstem.

117 f the cornea contains the highest density of nociceptive nerves of any tissue in the body.

118 s revealed that while some features of adult nociceptive network activity are present in infants at l

119 which serve as a major output of the spinal nociceptive network and are essential for pain perceptio

120 of these sensory inputs to sensitize central nociceptive networks and thereby evoke persistent pain i

121 lectrophysiological analysis of infant brain nociceptive networks can provide further understanding o

122 PD-L1 also potently suppressed nociceptive neuron excitability in human DRGs.

123 eport provides a genetic analysis of primary nociceptive neuron mechanisms that promote sensitization

124 specifically in the Class IV multidendritic nociceptive neuron, significantly attenuated ultraviolet

125 Given the significant role of Slack in nociceptive neuronal excitability, the AP-2 clathrin-med

126 ive neurons were also immunopositive for the nociceptive neuronal markers IB4, TRPV1, CGRP, and subst

127 nkyrin 1 (TRPA1) ion channel is expressed in nociceptive neurons and its activation causes ongoing pa

128 ales acute noxious mechanical sensitivity in nociceptive neurons and suppresses neuropathic pain tran

129 of ecto-5'-nucleotidase (CD73) in trigeminal nociceptive neurons and their axonal fibers, including t

130 modulation of presynaptic TRPV1 channels in nociceptive neurons by descending noradrenergic inputs m

131 PD-1 activation in DRG nociceptive neurons by PD-L1 induced phosphorylation of

132 review how non-neuronal cells interact with nociceptive neurons by secreting neuroactive signaling m

133 tion of MOG results in aberrant sprouting of nociceptive neurons in the spinal cord.

134 small subpopulations of pruriceptive and/or nociceptive neurons innervating the cheek project to tha

135 Pulpitis and osteitis affected the nociceptive neurons innervating the orofacial region by

136 was observed in a subpopulation of putative nociceptive neurons innervating the site of inflammation

137 lation of TRPV1 channels by noradrenaline in nociceptive neurons is a mechanism whereby noradrenaline

138 modulation of TRPV1 channels by dopamine in nociceptive neurons may represent a way for dopamine to

139 potential cation channel V1 expressed in the nociceptive neurons of dorsal root ganglion (DRG).

140 tained protease signaling to colonocytes and nociceptive neurons that naturally express PAR2 and medi

141 ansient receptor potential (TRP) channels of nociceptive neurons to induce neurogenic inflammation an

142 Results suggest that nociceptive neurons use the BMP2/4 ligand, along with id

143 TRPV1, a PGE2-regulated channel in nociceptive neurons was also increased in the DRG.

144 Drosophila melanogaster larvae whose primary nociceptive neurons were reduced in levels of specific c

145 e, type C low-threshold mechanosensitive and nociceptive neurons with markedly different molecular an

146 edge of the molecular composition of KARs in nociceptive neurons, a key piece in understanding the me

147 by changes in the excitability of peripheral nociceptive neurons, but the precise mechanisms controll

148 itatory postsynaptic currents in spinal cord nociceptive neurons, increased CGRP release from sciatic

149 n modulate the activity of TRPV1 channels in nociceptive neurons, the effects of dopamine and dopamin

150 Alkaline pH evokes an inward current in nociceptive neurons, which is primarily mediated by TMC-

151 ted cation channel acting as key receptor in nociceptive neurons.

152 between cranial sensory neurons and the PBL-nociceptive neurons.

153 brainstem to drive feedforward inhibition of nociceptive neurons.

154 ion of a neuronal-specific gene set, notably nociceptive neuropeptides.

155 ting mechanosensory input facilitate primary nociceptive output by releasing short neuropeptide F, th

156 ation leads to ROS production and subsequent nociceptive pain in mice.

157 behavior in models of inflammatory and acute nociceptive pain was normal.

158 Previous work, using models of acute nociceptive pain, indicated that analgesia by acetaminop

159 or underlying mechanism (eg, painful cramps, nociceptive pain, or neuropathic pain).

160 captured by a previous fMRI-based marker for nociceptive pain.

161 Opioid receptors are important modulators of nociceptive pain.

162 y-induced hypersensitivity without affecting nociceptive pain.

163 own downstream neural circuit components for nociceptive (pain-like) behavior in Drosophila larvae.

164 The TRPA1 ion channel is expressed in nociceptive (pain-sensitive) neurons and responds to a w

165 ctivation by adenosine as an endogenous anti-nociceptive pathway and support the development of A3AR

166 an important relay center for the descending nociceptive pathway through the rostral ventral lateral

167 lular adenosine generation in the trigeminal nociceptive pathway.

168 a I neurons, the first synaptic relay in the nociceptive pathway.

169 have opposing effects on nociceptive vs. non-nociceptive pathways and suggest that cannabinoid-based

170 ng muscle appear more capable of sensitizing nociceptive pathways in the CNS compared with skin affer

171 age during early life can "prime" developing nociceptive pathways in the CNS, leading to greater pain

172 molecular basis for long-term alterations in nociceptive pathways induced by polyarthritis using the

173 Augmentation of synaptic strength in nociceptive pathways represents a cellular model of pain

174 g the neonatal period can "prime" developing nociceptive pathways such that a subsequent injury durin

175 f Vc/C2 could lead to enhanced activation of nociceptive pathways, contributing to the development of

176 ptor (Adcyap1r1) are expressed in peripheral nociceptive pathways, participate in anxiety-related res

177 ion of pain, but gated activity in ascending nociceptive pathways.

178 out the synaptic effects of buprenorphine in nociceptive pathways.

179 calcium influx, hyperalgesia and induced pro-nociceptive peptide release.

180 The anti-nociceptive potential of these complexes and the free li

181 op into inhibitory neurons, are activated by nociceptive primary afferents, and form GABA-A-mediated

182 cation or sustained electrical activation of nociceptive primary sensory nerve fibres.

183 oup of rat SSDHN following the activation of nociceptive primary sensory neurons by burn injury, caps

184 eripheral mechanism that can regulate spinal nociceptive processing and pain sensation.

185 individuals, marked by facilitated ascending nociceptive processing and/or reduced capacity for desce

186 bed, the brain structures involved in infant nociceptive processing are completely unknown, meaning w

187 e propose that p-S10H3 is a novel marker for nociceptive processing in SSDHN with high relevance to t

188 Our understanding of nociceptive processing in the infant brain has been adva

189 Descending controls on spinal nociceptive processing play a pivotal role in shaping th

190 is an important center that controls spinal nociceptive processing, on which secondary hypersensitiv

191 ripherally induced itch without compromising nociceptive processing.

192 ith the extent of imbalance toward ascending nociceptive processing.

193 an underlying modular architecture in which nociceptive, pruritic, and innocuous stimuli are process

194 In adults, nociceptive reflexes and behavioral responses are modula

195 nociceptive role for GPR55 in the control of nociceptive responding.

196 nanoparticles (NM0127) showed a strong anti-nociceptive response in multiple assays of evoked and on

197 The nociceptive response is limited by enkaphalin-expressing

198 In the absence of verbal report, these nociceptive responses are used as measures of pain sensa

199 lacement attenuated TMJ inflammation and the nociceptive responses in a dose-dependent manner in the

200 These data suggest that the enhanced nociceptive responses in AS model mice are due to loss o

201 ally to mice, CGRP8-37-cholestanol inhibited nociceptive responses to intraplantar injection of capsa

202 Nociceptive responses to select noxious thermal and mech

203 sion in DRGs neurons and to evaluate whether nociceptive responses were affected in AS model mice (gl

204 d in male and female AS model mice; however, nociceptive responses were not altered by the conditiona

205 of stress exhibit larger amplitude cortical nociceptive responses, but this is not reflected in thei

206 ed PACAP-induced CeA neuronal activation and nociceptive responses.

207 in higher level cognitive processes or basic nociceptive responses.

208 op mechanical hyperalgesia, suggesting a pro-nociceptive role for GPR55 in the control of nociceptive

209 Using Drosophila larvae, we found that nociceptive rolling behavior was triggered at lower temp

210 dying the electrophysiological properties of nociceptive sensitization and potentially related condit

211 Nociceptive sensitization is a common feature in chronic

212 Because nociceptive sensitization is associated with chronic pai

213 tory lipid mediator whose role in peripheral nociceptive sensitization is not well understood to date

214 required for modulation of an injury-induced nociceptive sensitization pathway presumably downstream

215 nucleotide-gated (HCN) channels play in this nociceptive sensitization using the inhibitors MK-801 an

216 s of the SMAD signal transduction pathway in nociceptive sensitization was also demonstrated.

217 Hedgehog, another key regulator of nociceptive sensitization, was produced by nociceptive s

218 its pathway play a crucial and novel role in nociceptive sensitization.

219 hy, and it is an effective antagonist of the nociceptive sensor channel TRPA1.

220 e possibility that optogenetic inhibition of nociceptive sensory afferents could be used to modulate

221 To study of the role of nociceptive sensory afferents in freely behaving mice, w

222 We found that optogenetic inhibition of nociceptive sensory afferents reduced both ongoing pain

223 Optically silencing nociceptive sensory afferents significantly blunted the

224 Downstream of the nociceptive sensory input, the neural signals trigger pr

225 nin gene-related peptide (CGRP), a marker of nociceptive sensory nerves.

226 ved in pain generation and modulation in the nociceptive sensory nervous system.

227 f nociceptive sensitization, was produced by nociceptive sensory neurons following tissue damage.

228 n of mechanosensory input from innocuous and nociceptive sensory neurons is required for robust mecha

229 Organisms rely on nociceptive sensory neurons to detect and avoid potentia

230 oth receptors are predominantly expressed in nociceptive sensory neurons, and an increase in extracel

231 tream of Hedgehog-dependent sensitization in nociceptive sensory neurons.

232 iosis might be involved in the activation of nociceptive sensory pathways, but there have been few st

233 ility to detect noxious stimuli, process the nociceptive signal, and elicit an appropriate behavioral

234 interaction between ascending spinocortical nociceptive signaling and the descending control of the

235 ndocannabinoid system is thought to modulate nociceptive signaling making it a potential therapeutic

236 subfamily V, receptor 1 (TRPV1)-substance P nociceptive signaling pathway.

237 ed to study and manipulate somatosensory and nociceptive signaling pathways.

238 isms underlying these differences in central nociceptive signaling remain incompletely understood, as

239 proinflammatory receptor that contributes to nociceptive signaling via the modulation of macrophages,

240 mission in the spinal cord dorsal horn gates nociceptive signaling, is essential in maintaining physi

241 lloid 1 (TRPV1) is involved in sensory nerve nociceptive signaling.

242 ve inputs, influence the spinal summation of nociceptive signals contributing to sex/inflammation-dep

243 tial step in transforming transient afferent nociceptive signals into a stable pain perception.

244 Nociceptive-specific brain activity increases in magnitu

245 From approximately 35 weeks' gestation, nociceptive-specific patterns of brain activity emerge [

246 3R mediated facilitation of both tactile and nociceptive spinal activity in the first three postnatal

247 erience intense pain with minimal peripheral nociceptive stimulation and others experience minimal pa

248 e (isolation from the dam in infancy, versus nociceptive stimulation in adults).

249 nate either the intensity or the location of nociceptive stimuli (1) occurs during practice and is su

250 G and anandamide diminished sensitization to nociceptive stimuli although the effects of 2-AG were lo

251 h endocannabinoids enhanced responses to non-nociceptive stimuli and reduced responses to nociceptive

252 Physiological responses to nociceptive stimuli are initiated within tens of millise

253 model of fibromyalgia to innocuous and acute nociceptive stimuli by applying a step-wise graded elect

254 behavioral responses to nociceptive vs. non-nociceptive stimuli in vivo.

255 ion of the intensity and spatial location of nociceptive stimuli is essential to guide appropriate be

256 ating both the intensity and the location of nociceptive stimuli occurs, and is maintained for at lea

257 Sensitized responses to non-nociceptive stimuli were unaffected 2-AG or anandamide.

258 melanogaster larvae respond to a variety of nociceptive stimuli, including noxious touch and tempera

259 In contrast, brief thermal or mechanical nociceptive stimuli, which fail to induce tissue injury

260 nvolved in the detection and transduction of nociceptive stimuli.

261 nociceptive stimuli and reduced responses to nociceptive stimuli.

262 r changes in response to nociceptive and non-nociceptive stimuli.

263 Accepting reward coupled to a nociceptive stimulus resulted in decreased perceived int

264 cleus and the periaqueductal gray, important nociceptive structures.

265 l mechanisms that feed back onto the primary nociceptive synapse and enhance the transfer of noxious

266 ech), endocannabinoids were found to depress nociceptive synapses, but enhance non-nociceptive synaps

267 epress nociceptive synapses, but enhance non-nociceptive synapses.

268 pecialization of DPANs within the trigeminal nociceptive system and 2) to recognize exclusive molecul

269 ization and network hyperexcitability of the nociceptive system is a basic mechanism of neuropathic p

270 Objective: To assess the integrity of nociceptive system processes in persons with DE and ocul

271 thways in regulating the excitability of the nociceptive system.

272 ive behavior, but the evolutionary origin of nociceptive systems is not well understood.

273 planarians to humans, and imply that animal nociceptive systems may share a common ancestry, tracing

274 l stimulus changes revealing a mechanism for nociceptive temporal contrast enhancement (TCE).

275 minant role in capsaicin-induced ablation of nociceptive terminals and further our understanding of t

276 necessary for capsaicin-induced ablation of nociceptive terminals.

277 of the spinal cord play an important role in nociceptive, thermal, itch and light touch sensations.

278 s and upon intra-PAG microinjection, reduces nociceptive threshold in the hot-plate test.

279 d to surgical tail resections and mechanical nociceptive thresholds (MNT) were measured in the acute

280 ly attenuates the generation of MIH and anti-nociceptive tolerance, and increases neurotransmission a

281 s responsible for generation of MIH and anti-nociceptive tolerance.

282 contribute to the generation of MIH and anti-nociceptive tolerance.

283 morphine-induced hyperalgesia (MIH) and anti-nociceptive tolerance.

284 volved in neurosensory processing, including nociceptive transduction.

285 IFN-alpha also inhibited nociceptive transmission by reducing capsaicin-induced i

286 yet produced a net inhibitory effect on the nociceptive transmission due to the filtering effect at

287 internal states by descending modulation of nociceptive transmission in the spinal cord.

288 IFN-alpha, produced by astrocytes, inhibits nociceptive transmission in the spinal cord.

289 the primary synapse, resulting in increased nociceptive transmission to higher brain centers.

290 al neurons, which serve as a major source of nociceptive transmission to the brain.

291 ote the excessive amplification of ascending nociceptive transmission to the mature brain and thereby

292 vor the excessive amplification of ascending nociceptive transmission to the mature brain in response

293 While glial activation and altered nociceptive transmission within the spinal cord are asso

294 mediate Cav2.2 channel inhibition and alter nociceptive transmission.

295 he ascending projections of pruriceptive and nociceptive trigeminal and spinal neurons.

296 urons of murine dorsal root ganglia that pro-nociceptive TRPM3 channels, present in the peripheral pa

297 tial conduction along the axonal membrane of nociceptive, unmyelinated peripheral nerve fibers, but c

298 ndocannabinoids can have opposing effects on nociceptive vs. non-nociceptive pathways and suggest tha

299 rectional effects on behavioral responses to nociceptive vs. non-nociceptive stimuli in vivo.

300 algesic mechanism within this early temporal nociceptive window.