INT85017

Context Info Confidence 0.67 First Reported 1999 Last Reported 2010 Negated 0 Speculated 0 Reported most in Abstract Documents 13 Total Number 18 Disease Relevance 7.56 Pain Relevance 10.86

plasma membrane (Mc4r) signal transducer activity (Mc4r)

Anatomy Link Frequency spinal cord 2 spinal 1 DRG 1 Mc4r (Rattus norvegicus)

Pain Link Frequency Relevance Heat Thermal hyperalgesia 8 99.92 agonist 16 99.82 Spinal cord 18 99.68 Pain 22 99.44 Morphine 15 99.30 Brush evoked pain 4 98.92 narcan 3 98.80 Eae 22 98.60 Dorsal horn 4 98.44 adenocard 6 98.28

Disease Link Frequency Relevance Heat Hyperalgesia 10 99.92 Non-diabetic Peripheral Neuropathy 4 99.66 Nociception 12 99.36 Neuropathic Pain 32 99.08 Injury 26 98.60 Apoptosis 2 95.16 INFLAMMATION 2 94.36 Pain 20 93.76 Body Weight 31 78.36 Infection 18 76.80

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

Compared to naive control animals, immunohistochemistry revealed a 40% and 22% increase in MC4 receptor-immunoreactivity (IR) in the dorsal horn of the spinal cord ipsilateral to the injury at 3 and 14 days after CCI, respectively.

Positive_regulation (increase) of MC4 in spinal cord associated with eae, injury, dorsal horn and spinal cord

1) Confidence 0.67 Published 2009 Journal Pharmacol Rep Section Abstract Doc Link 20081244 Disease Relevance 1.12 Pain Relevance 1.17

Glutamatergic receptors, ghrelin precursor, melanocortin 4 receptor (MC4-R) and neuroligin 1 were found to be up-regulated in the responder group which may become new targets for nociceptive study and deserve further investigation for developing new acupuncture therapy and intervention of pain modulation.

Positive_regulation (up-regulated) of melanocortin 4 receptor associated with nociception, pain and acupuncture

2) Confidence 0.50 Published 2007 Journal Am. J. Chin. Med. Section Abstract Doc Link 17963317 Disease Relevance 0.38 Pain Relevance 0.71

Glutamatergic receptors, ghrelin precursor, melanocortin 4 receptor (MC4-R) and neuroligin 1 were found to be up-regulated in the responder group which may become new targets for nociceptive study and deserve further investigation for developing new acupuncture therapy and intervention of pain modulation.

Positive_regulation (up-regulated) of MC4-R associated with nociception, pain and acupuncture

3) Confidence 0.50 Published 2007 Journal Am. J. Chin. Med. Section Abstract Doc Link 17963317 Disease Relevance 0.38 Pain Relevance 0.71

First, a library of 18 peptides, in which a melanocortin-based sequence was systematically point-mutated, was screened for binding to and activity on the MC3R, MC4R and MC5R.

Positive_regulation (screened) of MC4R

4) Confidence 0.50 Published 2003 Journal Peptides Section Abstract Doc Link 12668212 Disease Relevance 0.22 Pain Relevance 0.18

Similarly, in the ipsilateral L4-L5 DRG, a 21.1% enhancement in MC4 receptor-IR was seen 3 days after CCI, as well as a 40.5% increase 14 days after CCI.

Positive_regulation (enhancement) of MC4 in DRG associated with eae

5) Confidence 0.49 Published 2009 Journal Pharmacol Rep Section Abstract Doc Link 20081244 Disease Relevance 1.14 Pain Relevance 1.21

Together, painful neuropathy resulted in the up-regulation of MC4 receptors in the spinal and peripheral nociceptive pathways.

Positive_regulation (up-regulation) of MC4 in spinal associated with nociception and pain

6) Confidence 0.45 Published 2009 Journal Pharmacol Rep Section Abstract Doc Link 20081244 Disease Relevance 1.06 Pain Relevance 1.14

This up-regulation of MC4 receptors promotes the pronociceptive action of their endogenous ligands.

Positive_regulation (up-regulation) of MC4

7) Confidence 0.45 Published 2009 Journal Pharmacol Rep Section Abstract Doc Link 20081244 Disease Relevance 0.97 Pain Relevance 1.06

This decrease was attenuated following chronic morphine administration, and mRNA level of MC4 receptors was gradually increased and, on 9th day of morphine administration, i.e. in the period when morphine tolerance already developed, the level was significantly increased in comparison with control and with the effect after single morphine dose.

Positive_regulation (increased) of MC4 associated with tolerance and morphine

8) Confidence 0.41 Published 2003 Journal Brain Res. Section Abstract Doc Link 14568335 Disease Relevance 0 Pain Relevance 1.69

MSH4 reached 50% of MC4R activation at a dilution of 216 times, while VWF-?

Positive_regulation (activation) of MC4R

9) Confidence 0.38 Published 2010 Journal BMC Neurosci Section Body Doc Link PMC2928777 Disease Relevance 0.06 Pain Relevance 0

Supernatants of both constructs activated the MC4R, with the polymeric VWF-?

Positive_regulation (activated) of MC4R

10) Confidence 0.33 Published 2010 Journal BMC Neurosci Section Body Doc Link PMC2928777 Disease Relevance 0.05 Pain Relevance 0

Activation of the MC4R was determined using LacZ as a reporter gene [36].

Positive_regulation (Activation) of MC4R

11) Confidence 0.33 Published 2010 Journal BMC Neurosci Section Body Doc Link PMC2928777 Disease Relevance 0 Pain Relevance 0.08

Activation of MC4R in vitro results in an increase in cyclic adenosine monophosphate (cAMP)[27].

Positive_regulation (Activation) of MC4R associated with adenocard

12) Confidence 0.26 Published 2010 Journal BMC Neurosci Section Body Doc Link PMC2928777 Disease Relevance 0 Pain Relevance 0.12

The secreted peptides were also biologically active since the medium could, respectively, inhibit or activate the MC4R.

Positive_regulation (activate) of MC4R

13) Confidence 0.26 Published 2010 Journal BMC Neurosci Section Body Doc Link PMC2928777 Disease Relevance 0 Pain Relevance 0.09

The supernatant of GFP transfected cells was not able to activate the MC4R (Figure 1D,E).

Positive_regulation (activate) of MC4R

14) Confidence 0.24 Published 2010 Journal BMC Neurosci Section Body Doc Link PMC2928777 Disease Relevance 0.08 Pain Relevance 0

In attempts to identify putative ligand-receptor interactions that may be participating in the agonist induced stimulation of the MC4R, selected ligands were docked into a homology molecular model of the mMC4R.

Positive_regulation (stimulation) of MC4R associated with agonist

15) Confidence 0.18 Published 2004 Journal J. Med. Chem. Section Abstract Doc Link 15615519 Disease Relevance 0.06 Pain Relevance 0.48

In addition, the upregulation of POMC and MC4, in parallel with the presence of tactile allodynia and thermal hyperalgesia, further supports the idea of MC system involvement in nociception.

Positive_regulation (upregulation) of MC4 associated with nociception, brush evoked pain and thermal hyperalgesia

16) Confidence 0.13 Published 2003 Journal Brain Res. Mol. Brain Res. Section Abstract Doc Link 14559360 Disease Relevance 1.11 Pain Relevance 0.93

MC4 and POMC transcript were upregulated in the spinal cord of neuropathic rats, whereas MC3 and AgRP expression were unaffected.

Positive_regulation (upregulated) of MC4 in spinal cord associated with neuropathic pain and spinal cord

17) Confidence 0.09 Published 2003 Journal Brain Res. Mol. Brain Res. Section Abstract Doc Link 14559360 Disease Relevance 0.93 Pain Relevance 0.99

From these studies we conclude that the acute increased LSNA and MAP in response to i.c.v. leptin may be mediated by increased POMC and its subsequent production of breakdown product alpha-MSH and/or beta-endorphin and it is the subsequent action of alpha-MSH that increases MAP and LSNA by activation of the MC4 receptor.

Positive_regulation (activation) of MC4

18) Confidence 0.03 Published 1999 Journal Brain Res. Bull. Section Abstract Doc Link 10566984 Disease Relevance 0 Pain Relevance 0.27

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