INT74465

Context Info Confidence 0.46 First Reported 1998 Last Reported 2010 Negated 0 Speculated 1 Reported most in Abstract Documents 22 Total Number 23 Disease Relevance 8.51 Pain Relevance 13.63

nucleus (Nkx1-1) neurological system process (Nkx1-1)

Anatomy Link Frequency nerve 3 macrophage 1 CoAO 1 spinal 1 spinal cord 1 Nkx1-1 (Rattus norvegicus)

Pain Link Frequency Relevance Heat Calcitonin gene-related peptide 322 100.00 antagonist 167 100.00 bradykinin 4 100.00 substance P 315 99.98 spinal-cord stimulation 8 99.98 tetrodotoxin 2 99.98 nMDA receptor 31 99.84 MU agonist 3 99.56 medulla 9 99.52 qutenza 633 99.38

Disease Link Frequency Relevance Heat Nociception 71 99.50 Pressure And Volume Under Development 113 99.44 Hyperalgesia 34 99.24 Increased Venous Pressure Under Development 139 99.10 Hypoxia 8 99.08 INFLAMMATION 383 98.84 Aging 1 98.56 Nervous System Injury 1 98.54 Neurogenic Inflammation 213 96.60 Injury 13 96.44

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Event

Anatomy

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Speculation

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Disease term

The less active enantiomer L-796,325 did not block NK1 agonist evoked activity at up to 10 mg kg(-1) and had no effect on behavioural or electrophysiological changes following nerve injury, indicating that the effects of GR205171 were attributable to selective NK1 receptor blockade.

Negative_regulation (blockade) of NK1 in nerve associated with nervous system injury and agonist

1) Confidence 0.46 Published 1998 Journal Neuropharmacology Section Abstract Doc Link 9886676 Disease Relevance 0.33 Pain Relevance 0.54

Whereas the long-term (24 h) response of both receptors to recurrent hypoxia in piglet brainstem is similar, i.e. upregulation, the short-term (5 min) response to single or recurrent hypoxia, albeit in rats, is different: radiolabelled NK-1 receptors are greatly reduced, suggesting enhanced endocytosis, but mu-opioid receptors remain unchanged, implying unaltered endocytosis.

Negative_regulation (reduced) of NK-1 in brainstem associated with medulla, hypoxia and mu opioid receptor

2) Confidence 0.41 Published 2002 Journal Respir Physiol Neurobiol Section Abstract Doc Link 12106992 Disease Relevance 0.52 Pain Relevance 0.53

Peripheral NK1 receptor blockade did not alter endothelial expression of intercellular adhesion molecule-1 or local chemokine and cytokine production, but decreased polymorphonuclear cell and macrophage recruitment.

Negative_regulation (blockade) of NK1 in macrophage

3) Confidence 0.34 Published 2007 Journal Anesthesiology Section Body Doc Link 18043070 Disease Relevance 0.06 Pain Relevance 0

This suggests that EA-induced suppression of hyperalgesia is involved, at least partly, in the suppression of the spinal NK-1 receptors induced by sustained peripheral nociceptive input.

Negative_regulation (suppression) of NK-1 in spinal associated with nociception, hyperalgesia and electroacupuncture

4) Confidence 0.34 Published 2005 Journal Neurosci. Lett. Section Abstract Doc Link 15908113 Disease Relevance 0.85 Pain Relevance 0.97

RESULTS: Systemic and peripherally selective, but not intrathecal, NK1 receptor blockade reduced stress-induced antinociception (control: 177 +/- 9 g, L-733,060: 117 +/- 8 g, and control: 166 +/- 30 g, SR140333: 89 +/- 3 g; both P < 0.05, t test) without affecting baseline hyperalgesia.

Negative_regulation (blockade) of NK1

5) Confidence 0.34 Published 2007 Journal Anesthesiology Section Body Doc Link 18043070 Disease Relevance 0.08 Pain Relevance 0

We have examined the effect of a tachykinin NK1 and a bradykinin B2 antagonist, and a mu-opioid agonist on plasma extravasation observed in response to two differing nerve stimulating parameters (10 V, 1 ms, 2 Hz and 25 V, 2 ms, 10 Hz).

Negative_regulation (antagonist) of NK1 in nerve associated with mu agonist, antagonist and bradykinin

6) Confidence 0.27 Published 1998 Journal Neurosci. Lett. Section Abstract Doc Link 9857952 Disease Relevance 0.40 Pain Relevance 0.60

These observations demonstrate that blockade of NK-1 receptors over a three day period failed to significantly modify the course of experimental colitis.

Negative_regulation (blockade) of NK-1 associated with colitis

7) Confidence 0.27 Published 1998 Journal Regul. Pept. Section Abstract Doc Link 9533813 Disease Relevance 0.95 Pain Relevance 0.67

Depletion of NK1 receptors in the NTS due to either ageing or acute hypoxia correlates with a markedly reduced respiratory response to substance P.

Negative_regulation (Depletion) of NK1 in respiratory associated with aging, hypoxia and substance p

8) Confidence 0.20 Published 2000 Journal Clin. Exp. Pharmacol. Physiol. Section Abstract Doc Link 11071314 Disease Relevance 0.20 Pain Relevance 0.26

Only SP mRNA was increased significantly in T4 and brainstem during CoAO, while SCS decreased the mRNA levels of SP, NK-1 and TRPV1 significantly in T4 and the brainstem.

Negative_regulation (decreased) of NK-1 in CoAO associated with medulla and spinal-cord stimulation

9) Confidence 0.13 Published 2007 Journal Neurosci. Lett. Section Abstract Doc Link 17714867 Disease Relevance 0.39 Pain Relevance 0.75

Immunohistochemistry was employed to visualize NK1 receptors and pCREB in spinal cord sections.

Negative_regulation (visualize) of NK1 in spinal cord associated with spinal cord

10) Confidence 0.12 Published 2000 Journal Neurosci. Lett. Section Abstract Doc Link 10729626 Disease Relevance 0.07 Pain Relevance 0.19

In a separate population of 17 of 45 cells tested, brachial nerve stimulation evoked an excitatory response that was antagonized by blockade of NK1 receptors.

Negative_regulation (blockade) of NK1 in nerve

11) Confidence 0.11 Published 2002 Journal Eur. J. Neurosci. Section Abstract Doc Link 12372027 Disease Relevance 0.23 Pain Relevance 0.21

In addition, the internalization NK1 or NK3 receptor was reversible.

Negative_regulation (reversible) of NK1

12) Confidence 0.10 Published 2002 Journal Neuroscience Section Abstract Doc Link 12453476 Disease Relevance 0 Pain Relevance 0.39

Application of tetrodotoxin blocked NK1 receptor internalization induced by NMDA, demonstrating that the release of neurokinins is dependent of axon potential propagation.

Negative_regulation (blocked) of NK1 associated with tetrodotoxin

13) Confidence 0.10 Published 2002 Journal Neuroscience Section Abstract Doc Link 12453476 Disease Relevance 0 Pain Relevance 0.34

These effects were abolished by the combination of B2 and CGRP1 blockade as well as by B2 antagonism in capsaicinized rats, while NK1 blockade was ineffective.

Negative_regulation (blockade) of NK1

14) Confidence 0.07 Published 2001 Journal Peptides Section Abstract Doc Link 11390021 Disease Relevance 0.18 Pain Relevance 0.46

The effects of SP were partially blocked by both the neurokinin-1 (NK1) and neurokinin-2 (NK2) receptor antagonists.

Negative_regulation (antagonists) of NK1 associated with antagonist and substance p

15) Confidence 0.07 Published 1999 Journal Am. J. Physiol. Section Abstract Doc Link 10444445 Disease Relevance 0 Pain Relevance 0.61

It is possible that the presence of CTA on the N terminus of substance P reduces the NK1 selectivity of the peptide.

Negative_regulation (reduces) of NK1 associated with substance p

16) Confidence 0.05 Published 2007 Journal BMC Neurosci Section Body Doc Link PMC1878491 Disease Relevance 0.21 Pain Relevance 0.24

We propose that the lack of endogenous SP in naked mole-rats means that heat-evoked foot withdrawal is only mediated by AMPA receptors in naïve animals, but that in the presence of SP, NMDA receptor sensitization leads to their involvement in nociceptive signaling and therefore inhibition of either NK1 or NMDA receptors reverses SP-induced sensitization.

Negative_regulation (inhibition) of NK1 in foot associated with nociception, nmda receptor, withdrawal and substance p

17) Confidence 0.04 Published 2010 Journal PLoS ONE Section Body Doc Link PMC3006196 Disease Relevance 0.16 Pain Relevance 0.76

We further examined how the blockade of TRPV1, CGRP, neurokinin 1 (NK1), or CGRP/NK1 receptors in the periphery affected the CAP-evoked inflammation and what differences there were by using dose-response analyses of antagonistic effects.

Spec (examined) Negative_regulation (blockade) of NK1 associated with inflammation, qutenza and calcitonin gene-related peptide

18) Confidence 0.03 Published 2007 Journal Mol Pain Section Body Doc Link PMC2174436 Disease Relevance 0.42 Pain Relevance 1.10

The CAP-induced edema was also reduced by either blockade of CGRP or NK1 receptors, but the NK1 antagonist (spantide I) produced a much stronger inhibition of edema.

Negative_regulation (blockade) of NK1 associated with pressure and volume under development, qutenza, antagonist and calcitonin gene-related peptide

19) Confidence 0.03 Published 2007 Journal Mol Pain Section Body Doc Link PMC2174436 Disease Relevance 0.73 Pain Relevance 1.07

Comparison of their inhibitory effects by these doses shows that vasodilation following CAP injection could be reduced by blockade of CGRP or NK1 receptors.

Negative_regulation (blockade) of NK1 associated with qutenza, increased venous pressure under development and calcitonin gene-related peptide

20) Confidence 0.03 Published 2007 Journal Mol Pain Section Body Doc Link PMC2174436 Disease Relevance 0.77 Pain Relevance 1.15

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