INT117495

Context Info Confidence 0.38 First Reported 2004 Last Reported 2010 Negated 0 Speculated 0 Reported most in Body Documents 13 Total Number 16 Disease Relevance 7.93 Pain Relevance 4.24

mitochondrion (Pars2) translation (Pars2) ligase activity (Pars2) cytoplasm (Pars2)

Anatomy Link Frequency neurons 3 sensory neurons 2 mast cell 2 urinary bladder 1 poly 1 Pars2 (Mus musculus)

Pain Link Frequency Relevance Heat Substantia nigra 4 100.00 qutenza 70 99.84 Inflammation 333 99.24 Inflammatory stimuli 19 97.76 Hyperalgesia 24 97.08 allodynia 1 92.28 Inflammatory response 40 91.76 Thermal hyperalgesia 1 91.28 IPN 6 89.84 agonist 77 89.00

Disease Link Frequency Relevance Heat INFLAMMATION 390 99.24 Disease 43 98.76 Increased Venous Pressure Under Development 9 98.56 Coagulation Disorder 12 98.04 Multiple Organ Failure 36 97.78 Nociception 99 97.56 Hyperalgesia 25 97.08 Death 50 96.76 Cancer 24 96.72 Overactive Bladder 39 96.24

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

Several studies recently reported PARs expression on neurons and some of them demonstrated that these receptors could interfere with nociception.

Gene_expression (expression) of PARs in neurons associated with nociception

1) Confidence 0.38 Published 2009 Journal Pain Section Abstract Doc Link 19674841 Disease Relevance 0.71 Pain Relevance 0.58

Serine proteases such as thrombin, trypsin and mast cell tryptase can act on different cell types through protease-activated receptors (PARs).

Gene_expression (act) of PARs in mast cell

2) Confidence 0.33 Published 2009 Journal Pain Section Abstract Doc Link 19674841 Disease Relevance 0.46 Pain Relevance 0.33

The expression of PARs is altered during inflammation [21].

Gene_expression (expression) of PARs associated with inflammation

3) Confidence 0.16 Published 2007 Journal BMC Immunol Section Body Doc Link PMC2000913 Disease Relevance 0.88 Pain Relevance 0.40

Protease-activated receptors (PARs) 1 and 2 are expressed in capsaicin-sensitive sensory neurons, being anti- and pro-nociceptive, respectively.

Gene_expression (expressed) of PARs in sensory neurons associated with nociception and qutenza

4) Confidence 0.14 Published 2004 Journal J. Pharmacol. Sci. Section Abstract Doc Link 15037813 Disease Relevance 0.44 Pain Relevance 0.92

Aberrant expression of protease-activated receptors (PARs) has been associated not only with inflammation but with increased angiogenesis, tumor growth, and metastasis of various cancers [42-47].

Gene_expression (expression) of PARs associated with inflammation, cancer and metastasis

5) Confidence 0.13 Published 2007 Journal BMC Physiol Section Body Doc Link PMC1853107 Disease Relevance 0.74 Pain Relevance 0.23

One possibility is that the mast cells themselves express PARs and are susceptible to PAR-AP activation [78,79].

Gene_expression (express) of PARs in mast cells

6) Confidence 0.13 Published 2007 Journal BMC Immunol Section Body Doc Link PMC2000913 Disease Relevance 0.55 Pain Relevance 0.19

Therefore, in this experiment, it is not unexpected that we found that multiple organ failure results also in the formation of peroxynitrite and it is well known that the nuclear enzyme poly (ADP-Ribose) synthetase (PARS) activation can be a consequence of peroxynitrite production [46,47].

Gene_expression (synthetase) of PARS in poly associated with multiple organ failure

7) Confidence 0.12 Published 2010 Journal J Inflamm (Lond) Section Body Doc Link PMC2844385 Disease Relevance 0.55 Pain Relevance 0.13

All four PARs are present in the urinary bladder, and their expression is altered during inflammation.

Gene_expression (present) of PARs in urinary bladder associated with inflammation

8) Confidence 0.11 Published 2007 Journal BMC Immunol Section Abstract Doc Link PMC2000913 Disease Relevance 0.26 Pain Relevance 0.13

Four PARs have been cloned to date, and all four PARs are co-expressed in the mouse bladder urothelium [24], with PAR2 and PAR3 being the most abundant in the bladder epithelial layer.

Gene_expression (expressed) of PARs in bladder

9) Confidence 0.10 Published 2007 Journal BMC Physiol Section Body Doc Link PMC1853107 Disease Relevance 0.79 Pain Relevance 0.26

Expression of PARs in DRG neurons: immunohistochemistry

Gene_expression (Expression) of PARs in neurons

10) Confidence 0.05 Published 2010 Journal Mol Pain Section Body Doc Link PMC2956715 Disease Relevance 0 Pain Relevance 0

Expression of PARs in glia was difficult to detect unequivocally using ISH because of the small size of these cells and the scatter of silver grains.

Gene_expression (Expression) of PARs

11) Confidence 0.05 Published 2010 Journal Mol Pain Section Body Doc Link PMC2956715 Disease Relevance 0 Pain Relevance 0

Expression of PARs in DRG neurons: in situ hybridisation

Gene_expression (Expression) of PARs in neurons

12) Confidence 0.05 Published 2010 Journal Mol Pain Section Body Doc Link PMC2956715 Disease Relevance 0 Pain Relevance 0.11

The mRNA of all four PARs is expressed in sensory neurons [12].

Gene_expression (expressed) of PARs in sensory neurons

13) Confidence 0.05 Published 2010 Journal Mol Pain Section Body Doc Link PMC2956715 Disease Relevance 0.26 Pain Relevance 0.17

Thus, trypsin IV and p23 are inhibitor-resistant trypsins that can cleave and activate PARs, causing PAR(1)- and PAR(2)-dependent inflammation and PAR(2)-dependent hyperalgesia.

Gene_expression (activate) of PARs associated with hyperalgesia and inflammation

14) Confidence 0.04 Published 2007 Journal J. Biol. Chem. Section Abstract Doc Link 17623652 Disease Relevance 0.95 Pain Relevance 0.69

Thus, thrombin is capable of signaling through PARs[26], which are expressed throughout the body and known to be involved in vascular responses[27], embryonic development[28], and malignancies[29].

Gene_expression (expressed) of PARs in body

15) Confidence 0.04 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2791444 Disease Relevance 0.18 Pain Relevance 0.03

Tyrosine Hydroxylase, TH-positive neurons) in the substantia nigra pars compacta (SNc) and to reproduce neuropathological features of PD in mice [35], [36].

Gene_expression (reproduce) of substantia nigra pars compacta in SNc associated with substantia nigra and disease

16) Confidence 0.04 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2675062 Disease Relevance 0.94 Pain Relevance 0.05

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