The mechanism of action for psychotropics approved for pain conditions??

[JohnBoy2000]

Cymbalta is approved for treatment of pain conditions.
Some people swear by it - say it's the best.

What is the underlying pharmacodynamic action that incites this pain release?

Effexor is also used in this capacity.

Each act on serotonin, and noradrenaline.

But no serotonergic agent is approved for pain disorders - where there are plenty of tricyclics that are.

So - by logic - it must be noradrenaline, no?

So - would something like reboxetine theoretically work for someone being treated for pain with cymbalta??

 

[JohnBoy2000]

The other thing is; my housemate has been suffering from lower back pain for a long time.

One evening he smoked marijuana - said, for the first time in so long, after all sorts of physical therapy and treatment - he experienced pain relief.

Now - I actually made a threat a while ago about marijuana.
I don't remember if I asked about its use in pain treatment in that thread.

But - one website I was looking on, said it inhibits GABA - which in turn must incite NA/DA release.

So, is it the NE releasing property that acts to relieve pain?
If that mechanism is even correct?

 

[JohnBoy2000]

And then I gotta ask: GABA agents like pregabalin - they mimic GABA neurotransmitter actions - so they promote the inhibition for NE/DA, right?

But they are used as treatment agents for pain conditions?

Seems very contradictory...?

 

[Cotcha Yankinov]

SNRIs increase the effect of efferent projections that travel down the brainstem and inhibit the dorsal root ganglion (afferent projections) that carry pain up into the sensory cortex.

Pregablin is a voltage gated calcium channel antagonist, it decreases the release of inflammatory substances like substance P that can contribute to pain-amplification states. Some serotonergic ligands appear to be helpful for pain-amplification states as well but probably not for acute pain in a regular person.

 

[JohnBoy2000]

SNRIs increase the effect of efferent projections that travel down the brainstem and inhibit the dorsal root ganglion (afferent projections) that carry pain up into the sensory cortex.

Pregablin is a voltage gated calcium channel antagonist, it decreases the release of inflammatory substances like substance P that can contribute to pain-amplification states. Some serotonergic ligands appear to be helpful for pain-amplification states as well but probably not for acute pain in a regular person.

Do other noradrenergic agents act with a similar mechanism to SNRI's?

If not - what gives SNRI's this unique property?

I believe some really old school tricyclics like amitriptyline are approved for use in pain conditions also....
Or is that sleep conditions/IBS...

 

[Cotcha Yankinov]

SRI and NRI synergize well together, as do mu-opioid receptor activation and NRI (https://www.ncbi.nlm.nih.gov/pubmed/24578192), but I'm not read on the matter of NRI or SRI in isolation being effective for acute or chronic pain. I wouldn't be surprised if either SRI or NRI helped a bit in isolation though. This could also have to do with processing of the sensory cortex itself rather than just transmission through the spinal cord.

The tricyclics have action at toll-like receptors that are located on microglia - these microglia can cause and perpetuate chronic pain states. Therein is probably some of why amitriptyline is used for neuropathic pain https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2872682/

 

[sekio]

Norepinephrine reuptake inhibitors do have analgesic effects, they're just not what you'd think of as your typical "painkillers". It's been known for a while that, for instance, amphetamine can synergize with morphine/opioids to make them more effective painkillers (there's a famous cocktail use in palliative care that is effectively lots of opioids plus amphetamine/cocaine/methylphenidate plus some anti-nauseants to keep it all down). and amphetamine itself actually has a marked analgesic effect. That's part of the rationale for the development of drugs such as tapentadol which have both opioid and norepinephrine reuptake inhibitor activity.

Gabapentin and pregabalin both actually lack activity at GABA receptors, despite their names, and are instead voltage gated calcium channel modulators as stated. They do exert analgesic effects though.