INT49205

Context Info Confidence 0.67 First Reported 1993 Last Reported 2008 Negated 0 Speculated 1 Reported most in Abstract Documents 20 Total Number 21 Disease Relevance 10.28 Pain Relevance 8.71

Golgi apparatus (B3GAT1) carbohydrate metabolic process (B3GAT1)

Anatomy Link Frequency spinal 3 lymphocyte 2 smooth muscle 1 spinal cord 1 neural 1 B3GAT1 (Homo sapiens)

Pain Link Frequency Relevance Heat qutenza 11 100.00 agonist 5 100.00 substance P 35 99.98 Spinal cord 18 99.84 Hyperalgesia 18 99.82 nociceptor 6 99.62 c fibre 26 99.54 antagonist 26 99.40 Pain 18 99.40 spinal inflammation 50 99.20

Disease Link Frequency Relevance Heat Hyperalgesia 22 99.82 Cancer 9 99.76 Stress 5 99.50 Pain 14 99.40 Low Back Pain 54 99.20 Vomiting 2 98.60 Neuropathic Pain 6 98.58 Nociception 19 98.54 Increased Venous Pressure Under Development 4 98.52 INFLAMMATION 17 98.08

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

Upon stimulation substance P is released from C-fibre afferents, leading to activation of neurokinin-1 (NK1) receptors, mainly in laminae I/II neurons of the spinal dorsal horn [13].

Positive_regulation (activation) of NK1 in neurons associated with c fibre, spinal dorsal horn and substance p

1) Confidence 0.67 Published 2008 Journal Mol Pain Section Body Doc Link PMC2424039 Disease Relevance 0.92 Pain Relevance 1.10

Stimulation of NK1 receptors on the endothelium causes vasodilation mediated by nitric oxide.

Positive_regulation (Stimulation) of NK1 in endothelium associated with increased venous pressure under development

2) Confidence 0.67 Published 2000 Journal Jpn. J. Pharmacol. Section Abstract Doc Link 11202607 Disease Relevance 0.47 Pain Relevance 0.27

These results indicate that in rats i.c.v. but not intraparenchymal infusion of NGF induce mechanical and cold allodynia as well as heat hyperalgesia, which is mediated, at least in part, by activation of NK-1 receptors.

Positive_regulation (activation) of NK-1 associated with hyperalgesia, allodynia and nerve growth factor

3) Confidence 0.67 Published 2000 Journal Neurosci. Lett. Section Abstract Doc Link 10832021 Disease Relevance 0.48 Pain Relevance 0.79

These data are interpreted as evidence that the second phase of nociceptive scores in the formalin test is attributable at least partially to tonic activation of NK-1 receptors at the spinal level, whether because of a temporally limited release of substance P, for example only during the first phase, but a slow removal or breakdown of substance P, or, more likely, because of tonic release from primary afferents throughout the second phase.

Positive_regulation (activation) of NK-1 in spinal associated with nociception and substance p

4) Confidence 0.67 Published 1999 Journal J. Neurosci. Section Abstract Doc Link 10414986 Disease Relevance 0.29 Pain Relevance 0.31

Irrespective of the mechanism, it can be concluded that at least some of the persistent nociceptive effects associated with peripheral inflammation, or at least those provoked by subcutaneous injection of formalin, are mediated via continuous activation of NK-1 receptors at the level of the spinal dorsal horn; this may relate directly to mechanisms underlying prolonged nociceptive pains in humans.

Positive_regulation (activation) of NK-1 in spinal associated with nociception, inflammation and spinal dorsal horn

5) Confidence 0.67 Published 1999 Journal J. Neurosci. Section Abstract Doc Link 10414986 Disease Relevance 0.37 Pain Relevance 0.27

Evidence for tonic activation of NK-1 receptors during the second phase of the formalin test in the Rat.

Positive_regulation (activation) of NK-1 associated with nociceptor

6) Confidence 0.67 Published 1999 Journal J. Neurosci. Section Title Doc Link 10414986 Disease Relevance 0.15 Pain Relevance 0.35

These observations support the body of literature that indicate that sustained small fiber input yields a hyperalgesia through activation of spinal NMDA and NK1 receptors and that in turn a portion of this action is mediated by the spinal release of cyclooxygenase products.

Positive_regulation (activation) of NK1 in spinal associated with hyperalgesia

7) Confidence 0.67 Published 1993 Journal Agents Actions Suppl. Section Abstract Doc Link 8317344 Disease Relevance 0.27 Pain Relevance 0.44

Tachykinins mediate a variety of physiological processes in the gastrointestinal, pulmonary and genito-urinary tract mainly through the stimulation of NK1 and NK2 receptors.

Positive_regulation (stimulation) of NK1

8) Confidence 0.56 Published 2000 Journal Neuropeptides Section Abstract Doc Link 11049734 Disease Relevance 0.28 Pain Relevance 0.14

A series of 4-phenylisoquinolone derivatives were synthesized and evaluated for NK1 (substance P) antagonist activity.

Positive_regulation (evaluated) of NK1 associated with antagonist and substance p

9) Confidence 0.50 Published 1995 Journal J. Med. Chem. Section Abstract Doc Link 7543579 Disease Relevance 0 Pain Relevance 0.32

At the spinal cord level, NK1 receptors are activated during the synaptic transmission, especially in response to noxious stimuli applied at the receptive field of primary afferent neurons.

Positive_regulation (activated) of NK1 in spinal cord associated with spinal cord

10) Confidence 0.49 Published 1998 Journal Neuropeptides Section Abstract Doc Link 9571643 Disease Relevance 0.31 Pain Relevance 0.24

Antagonist studies show that the great proportion of the NANC neural mucus secretory response is mediated via NK1 receptors, with little or no contribution from NK2 receptors.

Positive_regulation (mediated) of NK1 in neural associated with antagonist

11) Confidence 0.49 Published 1995 Journal Can. J. Physiol. Pharmacol. Section Abstract Doc Link 8846433 Disease Relevance 0.32 Pain Relevance 0.45

NK1 receptors mediate tachykinin-induced increase in microvascular clearance in hamster cheek pouch.

Positive_regulation (mediate) of NK1 in cheek associated with qutenza

12) Confidence 0.49 Published 1993 Journal Am. J. Physiol. Section Title Doc Link 7690191 Disease Relevance 0 Pain Relevance 0.59

BACKGROUND: Animal studies suggest that substance P, a peptide that preferentially activates the neurokinin-1 (NK1) receptor, is involved in pain transmission, with particular importance in pain after inflammation.

Positive_regulation (activates) of NK1 associated with pain, inflammation and substance p

13) Confidence 0.49 Published 1998 Journal Clin. Pharmacol. Ther. Section Abstract Doc Link 9834049 Disease Relevance 0.37 Pain Relevance 0.44

Evidence for this is that co-activation of N-methyl-D-aspartate and NK1 receptors can produce long-lasting increases in the responses of STT cells, and antagonists of these receptors prevent central sensitization.

Positive_regulation (activation) of NK1 associated with spinothalamic tract, central sensitization and antagonist

14) Confidence 0.45 Published 2002 Journal Brain Res. Brain Res. Rev. Section Abstract Doc Link 12589918 Disease Relevance 0.32 Pain Relevance 1.14

These results indicate that transactivation of the EGF receptor as well as stimulation of the mitogen activated/extracellular signal-regulated protein kinase (ERK) are essential for substance P/NK-1 receptor-induced activation of Egr-1 biosynthesis.

Positive_regulation (activation) of NK-1 associated with substance p

15) Confidence 0.45 Published 2002 Journal Neurosci. Lett. Section Abstract Doc Link 12384223 Disease Relevance 0.43 Pain Relevance 0.49

CGRP requires access to its receptors on the cerebrovascular smooth muscle, while selective NK1 and NK2 receptor agonists increase CBF, probably indirectly via their bronchoconstrictor activity.

Spec (probably) Positive_regulation (increase) of NK1 in smooth muscle associated with agonist

16) Confidence 0.31 Published 1993 Journal Neuropeptides Section Abstract Doc Link 7688875 Disease Relevance 0 Pain Relevance 0.33

Significantly extended survival characteristics were observed among patients who displayed an expansion of a population of CD57, CD8 co-positive lymphocytes during therapy in comparison with those patients not displaying this peripheral blood lymphocyte (PBL) population expansion (34 mo vs. 12 mo, respectively, p = 0.04) and among those patients displaying disease stabilization or better as a clinical response (p = 0.001).

Positive_regulation (population) of CD57 in lymphocyte associated with disease

17) Confidence 0.30 Published 1993 Journal Semin Surg Oncol Section Abstract Doc Link 8516615 Disease Relevance 0.83 Pain Relevance 0.09

On the other hand, the three groups (elderly subjects, subjects faced with unresolved stress, and BZ consumers) show increase of the CD57 lymphocyte subset as well as natural killer cytotoxicity.

Positive_regulation (increase) of CD57 in lymphocyte associated with stress

18) Confidence 0.08 Published 1996 Journal Psychother Psychosom Section Abstract Doc Link 8843497 Disease Relevance 1.59 Pain Relevance 0.36

Indeed, the CD4+CD28- T cells from AS patients that we tested expressed high levels of CD57 and NK receptors, but they lacked expression of CD7, thus sharing typical NK cell features [39].

Positive_regulation (levels) of CD57 in T cells associated with spinal inflammation

19) Confidence 0.05 Published 2003 Journal Arthritis Res Ther Section Body Doc Link PMC193730 Disease Relevance 0.93 Pain Relevance 0.39

LCNEC was strongly positive for CD56, CD57, chromogranin A, synaptophysin, and P504S/alpha methylacyl CoA racemase.

Positive_regulation (positive) of CD57

20) Confidence 0.04 Published 2006 Journal Am. J. Surg. Pathol. Section Abstract Doc Link 16723845 Disease Relevance 0.88 Pain Relevance 0.08

General Comments

This test has worked.