Psycho-Babble Medication | about biological treatments | Framed
This thread | Show all | Post follow-up | Start new thread | List of forums | Search | FAQ

Addiction Proof Pain killer

Posted by zazenducke on September 12, 2012, at 16:59:51

Interesting article about an enantiomer of naloxone. Do you think people whose depression lessens on opiates would still feel relief if the pleasure producing effect was blocked and they were only recieving pain relief? Only testing in ratties of course.

.....

The study drug, (+)-naloxone, acts on glia, blocking a type of receptor called toll-like receptor 4 (TLR4), which is found on glial cells. Activation of this receptor appears to be important for both the pleasure and dependence-producing effects of opioids: when the receptor was blocked by (+)-naloxone, rodents didnt seek opioids or become tolerant to them. Blocking this receptor also enhanced opioids pain-relieving power.

But while giving (+)-naloxone to block TLR4 seemed to mitigate the development of opioid tolerance and withdrawal, mice that were bred to lack the TLR4 receptor altogether still experienced some withdrawal symptoms when opioids were stopped, suggesting that the function of the receptor doesnt fully account for opioid dependence.

Heres how the system may work: when exposed to opioid drugs like morphine, glial cells become active; in turn, they ramp up the activity of the neurons that respond to opioids, which are critical to pathways involved in pleasure and pain, explains Watkins. When this activity occurs in a pain pathway, glial activation amplifies pain. This counteracts what the opioid is trying to do for pain control, she says; morphine suppresses pain by acting on neurons, but it simultaneously enhances pain by activating glia. But since the morphine suppression is typically greater than the glial activation, the drug cuts pain overall.

Over time, with continue use of painkillers, however, glia become increasingly activated thats what reduces the drugs pain-relieving effect, producing tolerance and the need for larger and larger doses.

The same holds true for the neurons involved in opioid-related pleasure, according to Watkins; glial activation revs up the neurons, but now the neurons are in the reward pathway so you amplification of reward, she says. You can think of glia as volume controls. They can dial up pain. They can dial up drug reward.

And (+)-naloxone seems to turn glia down. Some types of chronic pain may in fact be caused by inflammation related to glia turning up pain circuits; earlier research by Watkins and colleagues has shown that (+)-naloxone can also counteract this type of pain, at least in rodents.

So far, (+)-naloxone has not been tested on humans. However, another drug that blocks TLR4 has undergone early stage clinical testing for use in addiction treatment to reduce withdrawal symptoms and block the opioid high. That drug, ibudilast, is already approved for other uses in Japan.

Potentially, ibudilast or a drug like (+)-naloxone could be added to prescription painkillers like OxyContin to increase pain relief, prevent the high and mitigate the development of tolerance and withdrawal upon cessation of use. Combinations are an interesting possibility, says Pasternak, adding that theres not enough data yet to know whether they would work.

Also, it is not clear whether preventing the high would hinder certain aspects of pain relief in humans. Subjective experiences of opioid use suggest that the high the relief of anxiety and sense of distance from the pain is not totally separate from the actual physical pain relief, and multiple previous efforts to dissociate the two have failed.

By itself, however, (+)-naloxone or a similar drug could be developed to treat chronic pain. We are trying to [raise the funds to] start a company to take this to clinical trials, says Watkins. There is a huge unmet need for effective therapies for chronic pain.

Of course, the long history of the quest for non-addictive opioids is one of repeated failure. Heroin was supposed to be a less addictive form of morphine, and OxyContin was supposed to be a less addictive pain reliever, too. But these new immune system connections are only just beginning to be explored and they may open up many new possibilities for relief.

Read more: http://healthland.time.com/2012/08/24/could-an-addiction-proof-painkiller-finally-be-on-the-horizon/#ixzz26IK1Dlu0



Share
Tweet  

Thread

 

Post a new follow-up

Your message only Include above post


Notify the administrators

They will then review this post with the posting guidelines in mind.

To contact them about something other than this post, please use this form instead.

 

Start a new thread

 
Google
dr-bob.org www
Search options and examples
[amazon] for
in

This thread | Show all | Post follow-up | Start new thread | FAQ
Psycho-Babble Medication | Framed

poster:zazenducke thread:1025514
URL: http://www.dr-bob.org/babble/20120912/msgs/1025514.html