Mechanosensory transduction, ATP, nerve excitability

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Mechanosensory transduction, ATP, nerve excitability

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Editorial - Purinergic mechanosensory transduction and visceral pain
Tuesday, 02 February 2010

BERKELEY, CA (UroToday.com) -

Interference with Mechanosensory Transduction May Provide Therapeutic Strategy for BPS

Visceral pain is one of the most common forms of pain associated with pathological conditions like dyspepsia, inflammatory bowel disease, angina, dysmenorrhoea, and bladder pain syndrome. In an enlightening review, Dr. Geoffrey Burnstock from London presents evidence to support the hypothesis that mechanosensory transduction occurs in tubes and sacs and can initiate visceral pain. The theory suggests that ATP released from epithelial cells during distension acts on P2X3 homomeric and P2X2/3 heteromeric receptors on subepithelial sensory nerves initiating impulses in sensory pathways to pain centers in the central nervous system.

Sensory information from the urinary bladder is conveyed by both lumbar splanchnic and sacral pelvic nerves to the spinal cord. Purinergic agonists increase the excitability of afferent fibers to distension. The roles of ATP released from urothelial cells and suburothelial myofibroblasts on various bladder functions have been established in several reviews, and evidence presented that urothelial-released ATP alters afferent nerve excitability. Increased extracellular ATP has a role in mechanosensory transduction and ATP-induced facilitation of the micturition reflex is mediated, at least partly, by nerves other than capsaicin-sensitive afferents.

Burnstock concludes that there is now strong evidence from several different laboratories that ATP is released from urothelial cells during distention of the bladder wall, activating sensory nerve endings beneath the urothelium via P2X3 and P2X2/3 receptors, leading via low threshold fibers to modulation of the voiding reflex and via high threshold fibers to reach pain centers in the central nervous system. He goes on to review similar findings for the ureter, gut, lung, uterus, tooth pulp, and tongue.

The review concludes on the hopeful note of potential therapeutic strategies based on purinergic pain theories. The search is on for selective P2X3 and P2X2/3 receptor antagonists that are orally bioavailable and do not degrade in vivo for the treatment of pain. Suramin is a drug developed by Oskar Dressel and Richard Kothe of Bayer, Germany in 1916, and is still sold by Bayer under the brand name Germanin. It is used for treatment of human sleeping sickness caused by trypanosomes and has been used in the treatment of onchocerciasis. Suramin is also one of many compounds used in research as a broad-spectrum antagonist of P2 receptors.

It has been claimed that opioids inhibit purinergic nociception in rat sensory neurons and fibers via a G protein-dependent mechanism. Cannabinoids act as inhibitory modulators of nociceptive responses produced by P2X2/3 receptors. Burnstock concludes this interesting report by noting that there are no publications to date describing clinical evaluations of P2 receptor antagonists and related purinergic compounds for the relief of pain, although clinical trials for some compounds are in progress. Compounds that inhibit ATP transport from epithelial cells or enhance ATP breakdown after its release may prove valuable in the treatment of visceral pain syndromes.

Burnstock G

Mol Pain. 2009 Nov 30;5:69

PubMed Abstract PMID: 19948030
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Sherradin
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Re: Mechanosensory transduction, ATP, nerve excitability

Post by Sherradin »

Would that explain why even if I take a very small amount of Endone (aust :Oxycodone hydrochloride) sometimes the pain can just evaporate for a day..the opioids effect the way the nervous system interpret the pain?
CPP since 2005. Prior to CPP always overly fit and active. I am female. Had two natural births: singleton 1998 and twins 2000. 2002 emergency back surgery - L5S1 herniation. Then recurring UTIs. Usual antibiotic overload. Then constant debilitating burning bladder and reaction to many foods. Australian Pain Clinic 2007. Turning point was Dec 2009 Attended Wise Clinic in Santa Rosa USA.
Was helped by strict diet but now eating normally after years of restricted diet - wonderful. Helped by: stretching,relaxation, yoga, trigger point, warm baths. Worsened by: stress, sitting, abdominal or glute exercises and salicylates
Medication: Now off all pain clinic meds no more Endone or Elavil only Lyrica 50 mg as Dec 2010 just reherniated L5S1disc and had discectomy. Its taken years but I feel I am over it.
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Re: Mechanosensory transduction, ATP, nerve excitability

Post by webslave »

Yes. I commented on the effect of opioids on the pain via the CNS in the archives:
viewtopic.php?f=9&t=707
viewtopic.php?f=37&t=6864&p=38231#p38231
Also see:
viewtopic.php?f=4&t=479&p=2396#p2396

Also a link to OCD:
viewtopic.php?f=9&t=6857&p=38181#p38181
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Re: Mechanosensory transduction, ATP, nerve excitability

Post by Sherradin »

That's so interesting. I spoke to Dr Wise and said I don't want to take these but I know in the past I have got off drugs too soon and it has added to the pain and wind up. He said that was an important self knowledge. So I figure at a 1/4 of a 5mg tab if thats working to halt the pain well its a good result. It there any way the oxycodone HCI could be acting as a muscle relaxant? as well. It does seem to switch off the pain in my mind..I am definitely a bit OCD perfectionist type but my bladder cannot tolerate any SSRI it burns it..only Elavil the older drugs or Lyrica as anti seizure drug helps...also CNS affecting drugs..you said in a previous post that there is some complex link here ..I bet they figure it out in the next ten years.
CPP since 2005. Prior to CPP always overly fit and active. I am female. Had two natural births: singleton 1998 and twins 2000. 2002 emergency back surgery - L5S1 herniation. Then recurring UTIs. Usual antibiotic overload. Then constant debilitating burning bladder and reaction to many foods. Australian Pain Clinic 2007. Turning point was Dec 2009 Attended Wise Clinic in Santa Rosa USA.
Was helped by strict diet but now eating normally after years of restricted diet - wonderful. Helped by: stretching,relaxation, yoga, trigger point, warm baths. Worsened by: stress, sitting, abdominal or glute exercises and salicylates
Medication: Now off all pain clinic meds no more Endone or Elavil only Lyrica 50 mg as Dec 2010 just reherniated L5S1disc and had discectomy. Its taken years but I feel I am over it.
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Re: Mechanosensory transduction, ATP, nerve excitability

Post by webslave »

I'm not aware of a link between opioids and muscle relaxation, but someone else may be able to post a link...
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