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Any other Analgesia Neurotransmitters/Receptors?

lemonman

Bluelighter
Joined
Sep 17, 2017
Messages
53
Hi,
I know the Alpha-2 adrenergic receptor is a Analgesia along with beta-endorphin.
Do you know of any others?
Thanks.
 
serotonin can also contribute to the analgesic acion of opioids,see tramadol.Calcium channels action can help with neuropathic pain
 
They both are receptors for glutamate which is an excitatory amino acid neurotransmitter. Many drugs that are antagonists to them have analgesic activity. I wouldnt say they cause pain exactly, rather are involved in the propagation of the pain signal.
 
NMDA antagonism is a good painkiller. Also activation of 5-HT receptors, norepinephrine receptors, etc are also analgesic to some extent (c.f. amphetamine is analgesic-sparing). Then there's cannabinoid receptors, the opioid receptors, maybe you'd count COX-2 as well.
 
Every pain-sensing nociceptor, although that "-ceptor" suffix is a bit of a misnomer since those are all ion channels.
 
Oh yeah, the Na+ channel that's blocked by lidocaine and friends is also a good analgesic target.
 
^Well, there are ionotropic and metabotropic receptors, are there not?
Yes, but nociceptors are not ligand-gated ion channels.

Some, however, can be activated by a ligand, but ligand binding is not a requirement for channel opening. E.g., TRPV1 responds to capsaicin and allyl isothiocyanate (the compounds in hot peppers and wasabi, respectively), but it also opens in response to high temperature, hence the sensation of burning when it's ligand-activated. AFAIK, pain receptors like NAv1.9 aren't ligand-activated, although some other pain-sensing sodium channels (NAv1.3 and NAv1.8 ) are known to be activated by certain toxins (based upon IUPHAR's coverage of these channels: http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=82 - see the detailed pages on those proteins).
 
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"We're sodium-channel blockers, we gotta stick together, man" (apologies to Dave Chapelle)
 
Yes, it augments the analgesic effect of opioids. When taken alone, it increases pain tolerance.

Please describe at as specific a quality as possible.

Also, there's literally a GABA POM in the mix for depression. I forget what it's exactly called, but they're trying to get it approved for major depression and postpartum depression, among other issues. Other than a high amount of anxiety leading to depression, the only thing that I could possibly link this to is how alprazolam and loprazolam have some sort of antidepressant effect, I'm assuming due to a2/a3 selectivity.
 
Please describe at as specific a quality as possible.

What do you mean by that?

In the event you're asking me to elaborate, its effect on opioids is to increase their analgesic effect - i.e., it augments their pain-numbing effect.

The effect on pain tolerance is to increase the threshold at which a response to pain occurs in, as an example, the tail flick test. I call this an increase in pain tolerance as opposed to an analgesic effect because amphetamine doesn't numb tactile sensitivity. In humans, that manifests as an increased ability to endure painful stimuli/sensations - i.e., following amphetamine administration, you might remain stoic to a sensation (e.g., post-operative pain) that would normally make you writhe in agony without an analgesic.

To be clear, I'm not sure whether it simply decreases responsiveness to painful stimuli (without affecting the sensation of pain) or decreases the sensation of pain (without affecting tactile sensitivity). It may do one or both of those things, but either way the net effect is to increase pain tolerance.
 
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^I believe some morphine patients have reported that they still feel the pain but simply care less about it, oddly.

But Ho-Chi, are you asking more about the specific bits in terms of progression of the pain signal up the spinal cord (dorsal root ganglion) and eventually into e.g. somatosensory cortex, and what role analgesic targets play in that scheme?
 
Delta opioid receptors play a pretty profound role in modulating (especially at the spinal level they are highly expressed) MOR-mediated analgesic responses, with DOR-agonists strongly potentiation antinociceptive effects of MOR agonists.

Anyone able to give me the latest consensus on the epsilon opioid receptor and the opioidergic 'lambda binding site' ?
I know a little about the former, but almost nothing about the latter.

As far as I can speak about morphine, dipropionylmorphine, etc. and oxycodone, prescribed the first and last of these, and plenty experience with DPM, and I can't say as when in acute pain (which without pain meds is always the case [being a chronic pain patient fucking sucks chocolate starfish] that it makes me 'care less' about pain which is still there. The pain from the bilateral trochanteric bursitis I have, and in my fucked up knee, the opiates actually get rid of it, rather than just make it less important. At least, given a sufficient dose, they do.
 
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Every pain-sensing nociceptor, although that "-ceptor" suffix is a bit of a misnomer since those are all ion channels.

Could you explain that simpler please? really trying to understand.

thanks.
 
I believe some morphine patients have reported that they still feel the pain but simply care less about it, oddly.

It can not be proved with animals experiment but ( at the moment) only with the psycological insight of a human, but I think it is clearly like this, it dumpens emotional response.
 
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