INT4985

Context Info Confidence 0.69 First Reported 1981 Last Reported 2010 Negated 4 Speculated 2 Reported most in Abstract Documents 81 Total Number 83 Disease Relevance 35.79 Pain Relevance 50.67

extracellular space (Tac1) extracellular region (Tac1) plasma membrane (Tac1)

Anatomy Link Frequency neurons 4 nerve 4 lungs 3 dorsal horn 3 striatum 2 Tac1 (Mus musculus)

Pain Link Frequency Relevance Heat substance P 655 100.00 Enkephalin 27 100.00 Dopamine 19 100.00 narcan 17 100.00 Calcitonin gene-related peptide 13 100.00 opioid receptor 6 100.00 Cannabinoid 2 100.00 agonist 101 99.98 Dynorphin 3 99.90 Sciatic nerve 52 99.84

Disease Link Frequency Relevance Heat Targeted Disruption 152 100.00 Bordatella Infection 4 100.00 Pulmonary Disease 78 99.88 Nicotine Addiction 29 99.84 Pruritus 9 99.84 Hyperalgesia 50 99.82 Bronchospasm 4 99.82 Cystitis 18 99.78 Pressure And Volume Under Development 13 99.60 Nociception 61 99.52

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

Partial sciatic nerve ligation was associated with mechanical allodynia, thermal hyperalgesia, and an increase in NK-1 mRNA on the ipsilateral, but not contralateral, side.

Positive_regulation (increase) of NK-1 mRNA in sciatic nerve associated with allodynia, thermal hyperalgesia and sciatic nerve

1) Confidence 0.69 Published 2004 Journal J Pain Section Abstract Doc Link 15042514 Disease Relevance 0.71 Pain Relevance 0.76

Capsaicin- and bradykinin-stimulated extravasation was attenuated by an NK1-receptor antagonist and is thus mediated by release of tachykinins and activation of the NK1 receptor.

Positive_regulation (activation) of NK1 associated with qutenza, antagonist and bradykinin

2) Confidence 0.67 Published 1997 Journal Am. J. Physiol. Section Abstract Doc Link 9142909 Disease Relevance 0.14 Pain Relevance 0.73

In contrast, CP-induced cystitis failed to upregulate the preprotachykinin-A and preproenkephalin genes which encode substance P and enkephalins, respectively in the hypothalamic and limbic nuclei at any of the time points examined.

Neg (failed) Positive_regulation (upregulate) of preprotachykinin-A associated with cystitis, enkephalin and substance p

3) Confidence 0.67 Published 2007 Journal Regul. Pept. Section Abstract Doc Link 17335920 Disease Relevance 0.48 Pain Relevance 0.65

Disruption of the substance P receptor (neurokinin-1) gene does not prevent upregulation of preprotachykinin-A mRNA in the spinal cord of mice following peripheral inflammation.

Positive_regulation (upregulation) of preprotachykinin-A in spinal cord associated with inflammation, spinal cord and substance p

4) Confidence 0.67 Published 1999 Journal Eur. J. Neurosci. Section Title Doc Link 10564361 Disease Relevance 0.59 Pain Relevance 1.02

These findings suggest that early stimulation of Tac1 is mediated by both genomic and non-genomic E2 pathways.

Positive_regulation (stimulation) of Tac1

5) Confidence 0.67 Published 2009 Journal Reprod Biol Endocrinol Section Body Doc Link PMC2724541 Disease Relevance 0.12 Pain Relevance 0.23

Therefore, it was interesting to observe that treatment with E2 for 3 h caused a parallel increase in both Tac1 and Tacr1 mRNAs.

Positive_regulation (increase) of Tac1

6) Confidence 0.67 Published 2009 Journal Reprod Biol Endocrinol Section Body Doc Link PMC2724541 Disease Relevance 0.16 Pain Relevance 0.24

Consistent with these findings, 3 h treatment with E2 caused an increase in Tac1 mRNA levels.

Positive_regulation (increase) of Tac1

7) Confidence 0.67 Published 2009 Journal Reprod Biol Endocrinol Section Body Doc Link PMC2724541 Disease Relevance 0.05 Pain Relevance 0.19

Besides SP, peptide hormones such as hemokinin can also bind and activate NK1 at sites of chronic inflammation [44].

Positive_regulation (activate) of NK1 associated with inflammation and substance p

8) Confidence 0.55 Published 2010 Journal Journal of Biomedicine and Biotechnology Section Body Doc Link PMC2817809 Disease Relevance 1.15 Pain Relevance 0.70

CONCLUSION AND IMPLICATIONS: The analgesic potential of morphine was increased in tac1 knockout mice.

Positive_regulation (increased) of tac1

9) Confidence 0.50 Published 2010 Journal Br. J. Pharmacol. Section Body Doc Link 20590634 Disease Relevance 0 Pain Relevance 0

NE neuronal burst activity was increased in NK1 null mutant and wildtype mice given RP67580, but not with RP68651.

Neg (not) Positive_regulation (increased) of NK1 in neuronal

10) Confidence 0.50 Published 2007 Journal Eur Neuropsychopharmacol Section Abstract Doc Link 16950604 Disease Relevance 0 Pain Relevance 0.24

Our results support the idea that substance P is an important mediator of thermal hypersensitivity in the setting of nerve injury and suggest that increased NK-1 receptor transcription precedes increased NK-1 receptor density, ultimately leading to behavioral hypersensitivity to peripheral thermal stimulation.

Positive_regulation (precedes) of NK-1 in nerve associated with nervous system injury, hypersensitivity and substance p

11) Confidence 0.50 Published 2004 Journal J Pain Section Abstract Doc Link 15042514 Disease Relevance 0.82 Pain Relevance 1.07

Our results support the idea that substance P is an important mediator of thermal hypersensitivity in the setting of nerve injury and suggest that increased NK-1 receptor transcription precedes increased NK-1 receptor density, ultimately leading to behavioral hypersensitivity to peripheral thermal stimulation.

Positive_regulation (increased) of NK-1 in nerve associated with nervous system injury, hypersensitivity and substance p

12) Confidence 0.50 Published 2004 Journal J Pain Section Abstract Doc Link 15042514 Disease Relevance 0.82 Pain Relevance 1.06

In conclusion, the 5-hydroxytryptamine-induced tracheal contraction includes a cholinergic mechanism that requires the presence of the tachykinin NK(1) receptor.

Positive_regulation (requires) of tachykinin

13) Confidence 0.49 Published 2007 Journal Pulm Pharmacol Ther Section Abstract Doc Link 16919985 Disease Relevance 0.23 Pain Relevance 0.33

PAR-2 agonists induce contraction of murine small intestine through neurokinin receptors.

Positive_regulation (induce) of neurokinin in small intestine associated with qutenza and agonist

14) Confidence 0.49 Published 2003 Journal Am. J. Physiol. Gastrointest. Liver Physiol. Section Title Doc Link 12801882 Disease Relevance 0 Pain Relevance 0.36

Gastric lesions are caused by an initial detrimental effect of EtOH, which is damaging only if associated with TRPV1 activation, SP release from sensory nerves, stimulation of neurokinin 1 receptors on epithelial cells, and ROS generation.

Positive_regulation (stimulation) of neurokinin 1 in epithelial cells associated with substance p

15) Confidence 0.49 Published 2007 Journal Free Radic. Biol. Med. Section Abstract Doc Link 17640568 Disease Relevance 0.07 Pain Relevance 0.47

These findings indicate that concurrent activation of spinal NMDA and substance P receptors induces an enhancement of spinal transmission of nociception, and that this enhancement is dependent on the intensity or the quality of the peripheral stimulus.

Positive_regulation (activation) of substance P in spinal associated with nociception and substance p

16) Confidence 0.49 Published 1992 Journal Pain Section Abstract Doc Link 1283010 Disease Relevance 0.17 Pain Relevance 0.29

Like N/OFQ, nocistatin-induced nociception was abolished by i.pl. injection of pertussis toxin, phospholipase C inhibitor, or CP-99994, a neurokinin 1 receptor antagonist, indicating that nocistatin may elicit nociception through a substance P release from nociceptor endings via activation of Gi/o and phospholipase C.

Positive_regulation (injection) of neurokinin 1 in nociceptor associated with nociception, bordatella infection, nociceptor, antagonist and substance p

17) Confidence 0.49 Published 2003 Journal J. Pharmacol. Exp. Ther. Section Abstract Doc Link 12665541 Disease Relevance 0.79 Pain Relevance 0.80

In conclusion, the NK1 receptor plays a functional role in mediating leukocyte accumulation independently of the historically important NK1 mediated oedema formation.

Positive_regulation (accumulation) of NK1 in leukocyte associated with pressure and volume under development

18) Confidence 0.48 Published 2006 Journal J. Neuroimmunol. Section Abstract Doc Link 16269189 Disease Relevance 0.39 Pain Relevance 0.36

As SP(5-11) did not down-regulate NK-1 binding, activation of NK-1 sites does not appear necessary or sufficient for down-regulation of SP binding.

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

19) Confidence 0.48 Published 1994 Journal Neurosci. Lett. Section Abstract Doc Link 7529387 Disease Relevance 0 Pain Relevance 1.14

Intracerebroventricular (i.c.v.) injection of NK1, NK2 or NK3 receptor antagonists (15-500 pmol/site), all produced significant and dose-dependent inhibition of both phases of the formalin and capsaicin tests.

Positive_regulation (injection) of NK1 associated with qutenza, antagonist and intracerebroventricular

20) Confidence 0.46 Published 1997 Journal Neuropeptides Section Abstract Doc Link 9308027 Disease Relevance 0.23 Pain Relevance 1.23

General Comments

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