SENSORY NERVE FIBERS,NOCICEPTORS

[Guest guest]

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POLYMODAL NOCICEPTOR FIBERS

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NOCICEPTORS

http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=neurosci & part=A676

2009 May;29(9):1896-904. Epub 2009 Apr 17.

TRPV1 controls acid- and heat-induced calcitonin gene-related peptide release

and sensitization by bradykinin in the isolated mouse trachea.

Kichko TI, Reeh PW.

Department of Physiology and Pathophysiology, University of Erlangen-Nuremberg,

Erlangen, Germany. kichko@...

Chronic cough derives from inflammatory hypersensitivity of tracheobronchial

nerve endings, most of which express the polymodal capsaicin receptor-channel

transient receptor potential vanilloid (TRPV) type 1 and the secretory

neuropeptide calcitonin gene-related peptide (CGRP). An isolated mouse trachea

preparation was established to measure chemically and thermally stimulated CGRP

release as an index for sensory transduction of potential cough-inducing

stimuli. TRPV1 knockout mice were employed to assess the TRPV1 contribution to

tracheal responsiveness and sensitization. Graded heat-induced CGRP release

depended entirely on extracellular calcium and partly on TRPV1; knockout mice

showed 60% less CGRP release at 45 degrees C (for 5 min) than wild-types. This

heat response was facilitated by the TRPV1 agonist ethanol and the TRPV1-3

agonist 2-aminoethoxydiphenyl borate, effects that were reduced or absent in

TRPV1(-/-), respectively. The TRPV1 antagonists ruthenium red and

N-(4-t-butylphenyl)-4-(3-chloropyridin-2-yl)

tetrahydropyrazine-1(2H)-carboxamide were ineffective on the basal heat

response. A step increase of temperature from 22 to 40 degrees C caused a

TRPV1-independent CGRP release that was doubled by bradykinin in wild-types but

not TRPV1(-/-). Proton stimulation resulted in a bell-shaped

concentration-response curve with threshold at pH 6.7 and a maximum at pH 5.7;

responses were greatly reduced but not abolished in TRPV1(-/-). Coadministration

of amiloride (30 microm), the blocker of acid-sensing ion channels, was

ineffective in both TRPV1 genotypes. The data suggest that tracheal acid sensing

mainly involves TRPV1 but not acid-sensing ion channels, whereas noxious heat

responsiveness partly depends and (inflammatory) sensitization to heat largely

depends on the capsaicin receptor in tracheal nerve endings. Lowering of their

heat threshold to near body temperature may sustain hypersensitivity and

neurogenic inflammation of the upper airways

2009 Jun;196(1):31-44. Epub 2009 Apr 30.

Differential effects of TRPV channel block on polymodal activation of rat

cutaneous nociceptors in vitro.

St Pierre M, Reeh PW, Zimmermann K.

Department of Physiology and Pathophysiology, Friedrich--University

Erlangen-Nuremberg, Universitätsstrasse 17, 91054 Erlangen, Germany.

The capsaicin receptor TRPV1 is a polymodal sensory transducer molecule in the

pain pathway. TRPV1 integrates noxious heat, tissue acidosis and chemical

stimuli which are all known to cause pain. Studies on TRPV1-deficient mice

suggest that TRPV1 is essential for acid sensing by nociceptors and for thermal

hyperalgesia in inflammation of the skin, but not for transducing noxious heat.

After TRPV1, other TRPV channels were cloned with polymodal properties and

sensitivity to noxious heat, named TRPV2, TRPV3 and TRPV4. While TRPV3 and TRPV4

are predominantly warm sensors, TRPV2's threshold is in the noxious range (>52

degrees C). However, mice deficient of TRPV2 and TRPV1 or TRPV3 or TRPV4 show no

major impairment of noxious heat sensing. Ruthenium red, a water soluble

polycationic dye, was found to block the pore of the capsaicin-operated cation

channel TRPV1 thus interfering with all polymodal ways of TRPV1 activation.

Antagonistic effects of the dye were subsequently described on many other

TRP-channels, especially on the heat-sensitive ones of the vanilloid family,

TRPV2, TRPV3 and TRPV4. In this study, we used the rat skin-nerve preparation to

define the possible actions of ruthenium red on the proton, capsaicin and

noxious heat activation of native polymodal nociceptors. Ruthenium red was found

to suppress only the capsaicin-induced excitation and desensitization of these

nerve endings. On the contrary, the proton and heat-induced discharge responses

of the single fibres were not influenced. Additionally, we found that the dye

concentration dependently increases the excitability of the neurons resulting in

ongoing activity and burstlike discharge. These differential results are

discussed in the light of recent findings from transgenic mouse models, and they

point once more to major (pharmacological) differences between cellular models

of nociception, including spinal ganglion neuron and transfected cell lines, and

the real native nerve endings.

C-polymodal nociceptors activated by noxious low temperature in human skin.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1161005/

PN'S,MONKEY 1976

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1307716/

Comparative Effects of the Nonsteroidal Anti-inflammatory Drug Nepafenac on

Corneal Sensory Nerve Fibers Responding to Chemical Irritation

http://www.iovs.org/cgi/content/full/48/1/182

Tear Secretion Induced by Selective Stimulation of Corneal and Conjunctival

Sensory Nerve Fibers

http://www.iovs.org/cgi/content/full/45/7/2333

Do fish have nociceptors: Evidence for the evolution of a

vertebrate sensory system

http://www.animalliberationfront.com/Practical/Fishing--Hunting/Fishing/fishfeel\

pain.pdf

[Guest guest]

PAIN HYPERSENSITIVITY

http://www.wellcome.ac.uk/en/pain/microsite/science4.html

>

> --------------------

> POLYMODAL NOCICEPTOR FIBERS

> ---------------------------

> NOCICEPTORS

> http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=neurosci & part=A676

>

> 2009 May;29(9):1896-904. Epub 2009 Apr 17.

>

> TRPV1 controls acid- and heat-induced calcitonin gene-related peptide release

and sensitization by bradykinin in the isolated mouse trachea.

> Kichko TI, Reeh PW.

>

> Department of Physiology and Pathophysiology, University of

Erlangen-Nuremberg, Erlangen, Germany. kichko@...

>

[Guest guest]

So is this Raynuads syndrome or something different because this one makes much

more sense

Good find J

>>>

TRPM8 Mechanism of Cold Allodynia after Chronic Nerve Injury

Cold allodynia is pathological pain induced by innocuous cold.

The pain is intractable and often occurs in patients with complex regional pain

syndrome; approximately 80% of these patients suffer from cold allodynia (Kemler

et al., 2000). Cold allodynia is also present in other disease conditions such

as fibromyalgia and diabetic neuropathy (Tahmoush et al., 2000; Vinik, 2004).

http://www.jneurosci.org/cgi/content/full/27/50/13680

Variable Threshold of Trigeminal Cold-Thermosensitive Neurons Is Determined by a

Balance between TRPM8 and Kv1 Potassium Channels

http://www.jneurosci.org/cgi/content/abstract/29/10/3120

=

[Guest guest]

I dont know, could play a role. denfinitly affects the hands and feet,my whole

body too. to me it seems this plays in more with the sensory sensitivity and

chemical intolerances and how my body can get so painful it hurts to be touched

with certain chemical exposures,ect. I did read something pertaining to vascular

effects somewhere along this line so it all ties together,maybe differences are

mostly to do with exposure, low dose long term showing mostly in the PNS vs.

high dose,more quicker damage,more overall nerve damage.

even though I always thought the fibromyalgia was because of toxins causeing

nerve damage, I still felt the actuall fibromyalgia presure points and

inflammation,vessels, caused by toxin exposure played more of a role in the

deeper ackeing muscle type effects but it basicly does all go together.

again there are immediate and delayed effects, so I have to think back to my

exposure, the beggening and yes, the nerves were being affected and yes, I could

have been diagnosed with fibromyalgia from the begenning. more obvious or

diagnosable while being exposed or for a while afterwards. yes, still, pocking

on those preshure points can cause me a world of pain, last time I let someone

anyway.

but now with advoidance, it's kept a bay unless somethings getting to me in a

more constant way, like several days and this flares up on it's own. but

re-exposures,some, can cause a immediate type pain

like the nasal steroid spray I tried, my face was instantly on fire and pain

than it just spread to the rest of my body, this hurts like hell and worse if

someone even touches me while this is going on.

the muscle ackes and felling like I was run over by a truck come later and I

know those preasure points are more sensitive at that point.

it must just be all about the immediate and delayed effects.

to me the tiny nerves closest to our skin ,causes this immediate pain the pain

where your skin basicly hurts. neuron buildup.

I dont know if I made a bet of sence there to anyone but myself.

it's interesting though, I'm thinking about those tv ads they use to run saying

fibromyalgia was overactive nerves, close, sensory hypersensitivity do to

damaged nerves. but I have to wonder this, are all people with fibromyalgia than

suffering at least some effects to the sensory system? seems so. I'm pretty

convienced fibromyalgia is caused by toxin exposure myself, unhalation, and I

can see how low dose long term toxin exposures could do this.

that really would make fibromyalgia a main part, maybe even the first sign of

toxin exposure and a warning of chemical hypersensitivity/TE to come. terrable

if thats true and they just crank out more drugs instead of getting the info out

there that it could be what your breathing.

>

> So is this Raynuads syndrome or something different because this one makes

much more sense

> Good find J

>

> >>>

>

> TRPM8 Mechanism of Cold Allodynia after Chronic Nerve Injury

>

>

>

> Cold allodynia is pathological pain induced by innocuous cold.

>

> The pain is intractable and often occurs in patients with complex regional

pain syndrome; approximately 80% of these patients suffer from cold allodynia

(Kemler et al., 2000). Cold allodynia is also present in other disease

conditions such as fibromyalgia and diabetic neuropathy (Tahmoush et al., 2000;

Vinik, 2004).

>

>

>

> http://www.jneurosci.org/cgi/content/full/27/50/13680

>

>

>

> Variable Threshold of Trigeminal Cold-Thermosensitive Neurons Is Determined by

a Balance between TRPM8 and Kv1 Potassium Channels

>

>

>

> http://www.jneurosci.org/cgi/content/abstract/29/10/3120

> =

>

[Guest guest]

Role of Metabolic Activation and the TRPA1 Receptor in the Sensory Irritation

Response to Styrene and Naphthalene

http://toxsci.oxfordjournals.org/content/115/2/589.abstract

Breathtaking TRP channels: TRPA1 and TRPV1 in airway chemosensation and reflex

control

Physiology (Bethesda, Md.), Vol. 23 (December 2008), pp. 360-370.

New studies have revealed an essential role for TRPA1, a sensory neuronal TRP

ion channel, in airway chemosensation and inflammation. TRPA1 is activated by

chlorine, reactive oxygen species, and noxious constituents of smoke and smog,

initiating irritation and airway reflex responses. Together with TRPV1, the

capsaicin receptor, TRPA1 may contribute to chemical hypersensitivity, chronic

cough, and airway inflammation in asthma, COPD, and reactive airway dysfunction

syndrome

http://physiologyonline.physiology.org/cgi/content/abstract/23/6/360

Heavy metals zinc, cadmium, and copper stimulate pulmonary sensory neurons via

direct activation of TRPA1

http://jap.physiology.org/cgi/content/abstract/108/4/891

Neuroinflammation in inflammatory bowel disease

Shaheen E Lakhan and Annette Kirchgessner

Published: 8 July 2010

Abstract

Inflammatory bowel disease is a chronic intestinal inflammatory condition, the

pathology of which is incompletely understood. Gut inflammation causes

significant changes in neurally controlled gut functions including cramping,

abdominal pain, fecal urgency, and explosive diarrhea. These symptoms are

caused, at least in part, by prolonged hyperexcitability of enteric neurons that

can occur following the resolution of colitis. Mast, enterochromaffin and other

immune cells are increased in the colonic mucosa in inflammatory bowel disease

and signal the presence of inflammation to the enteric nervous system.

Inflammatory mediators include 5-hydroxytryptamine and cytokines, as well as

reactive oxygen species and the production of oxidative stress. This review will

discuss the effects of inflammation on enteric neural activity and potential

therapeutic strategies that target neuroinflammation in the enteric nervous

system.

http://www.jneuroinflammation.com/content/7/1/37/abstract

Drosophila TRPA1 channel mediates chemical avoidance in gustatory receptor

neurons

http://www.pnas.org/content/107/18/8440.abstract

Nasal chemosensory cells use bitter taste signaling to detect irritants and

bacterial signals

http://www.pnas.org/content/107/7/3210.abstract