So you have the basic physiology down:
Noxious stimuli> Nociceptors > Primary Afferent Neuron> Dorsal Root Ganglion> Secondary Afferent Neuron> glutamate/ substance P, Hypothalamus, Thalamus, Limbic system (to learn pain avoidance in the future),Cortex, PAG, LC, RVM...
Opioids effect pain at multiple points; in the periphery to decrease activation of primary neurons while inhibiting immune/ inflammatory responses. Opioid activity between primary/ secondary neurons=reduced Ca ions released into synaptic cleft= decreased pain signal. Also having mood altering effects like sedation, decreased emotional response, euphoria; and If you're in pain, indifference to it def beats the alternative.
So you have G Coupled Proteins, G(a,b,y) inhibitory roles, Adenyl cyclase, cAMP, VDCC's, GIRK's, Receptor types: Mu 1&2, Delta 1&2, Kappa 1,2& 3=ORL-1, different combinations effecting spinal/supraspinal areas with interactions that are both synergistic and independent involving at least 6 receptor systems. This doesn't even account for a whole host of other processes that come into play.
Different opioids having different activation ratios regarding the aforementioned receptors is one reason they respond to pain as well as individuals differently.
All leading to... reduced nociception.
Now your not interested in COX-2 inhibitors or prostaglandin release or anything NSAID?
So I guess I'm curious if there's something more specific about opioids and how they work, or if maybe the complete extinguishing of pain by a nerve block is what you were referring to?
Sometimes it's easier to understand if you've been in severe pain and have more experience with them.
No offense. I`m not `into drugs`.
A couple of things. <some people> claim that drugs like ibuprofen, aspirin, paracetamol/acetominophen work well for pain caused by/associated with inflammation. Is that true ? I mean, a broken bone, a flesh wound, stomach pain caused by influenza etc. > that doesn?t cause inflammation, so NSAIDS do not work ? What Ive heard/read is that drugs like paracetamol and ibuprofen are supposed to be effective for that sort of pain. Maybe not 100 % ... For me: nothing.
Opiates are supposed to be effective for serious pain. No access to them when I was a kid and broke a leg ... more recent, pain was?t so severe and the best a strong opiate did was make me a bit indifferent. I did get a `glow? that I didn?t like in a certain way ...
The classical story is that people get morphine after a serious accident and their guts are spilled out ... the morphine works.
Is the explanation that `my body processes pain signals differently? ` For whatever reason.
First off, Apologies Qdar for not keeping up with this thread, I should have been checking in on it.
The reason drugs like Ibuprofen, Naproxen Sodium/ Na, Ketoprofen, Diclofenac, fenoprofen, meloxicam, oxaprozin, sulindac and to a lesser degree: APAP (tylenol), ASA (aspirin) work well for inflammation is in their name..
Non
Steroidal
Anti-
INFLAMMATORY
Drugs, or NSAID's. They work on pain where it starts by reducing inflammation or by mitigating the expression of COX/Cyclooxegenase-1 & 2. An Enzyme that catalyzes the conversion of arachidonic acid to prostaglandins and that has two isoforms of which one is involved in the creation of prostaglandins which mediate inflammation and pain.
One issue with COX 1 is that it also affects the protective lining of the stomach and therefore can cause some GI upset and/or ulcers with long term use. The selective COX-2 inhibitors (which doesn't reduce the protective lining of the stomach) known as Rofecoxib and Celecoxib were very effective, but due to a somewhat flawed study, were accused of causing heightened rates of cardiovascular incidents and strokes. Some believe that Rofecoxib & Celecoxib (Vioxx & Celebrex) were just as safe as Ibuprofen.
You Decide.
Much like Grampa after a brandy, I'm getting off track. So A broken bone and a flesh wound cause massive amounts of inflammation but you can't stop the pain by reducing inflammation alone when you have a compound fracture and torn muscle, nerve damage, soft tissue damage, even if it's just the bone there's the outer covering that's rich in nociceptors, the periosteum. Then the endosteum which gets fairly upset when you go breaking it. And it doesn't just have to be a simple transverse fracture like one that's at a right angle. Greenstick fractures occur when the bone is twisted, rupturing periosteal blood vessels/ nerves along the periosteum. I think you can see simply reducing the inflammation isn't going to cut it for pain control.
That doesn't mean they can't be helpful with other types of pain though like arthritis or sore muscles. When combined with opioids the synergism is much greater than the either one alone. Not that the practice of loading up desirable opioids with APAP to make them "more abuse resistant" is an ethical practice seeing as many a pill junkie with jaundice is floating around out there and the practice isn't slowing as now APAP is in cough medicine, cold medicine and just about any other otc med you can shake a stick at.
Best they die a horrible hepatoxic death if they plan to abuse the hydrocodone though, that's how we roll here with western medicine now.
But keep in mind NSAID's are pain reducers, not pain killers. Not even opioids act as true pain killers, more like pain distracters, which is a great option compared to nothing at all. Even with opioids being an excellent substance to "fake" our normal endorphins and are of much stronger effect, the body is a complex and sophisticated organism that still gets that there's pain happening. Aside from things like epidurals or nerve blocks that completely numb a certain area, there's no guarantee that a systemic medicine can block all pain unless it's making you unconscious.
If you've ever had Sufentanil I think you'd realize that your body processes pain signals in the same way as the rest of us. Nowadays getting sufficient pain relief from opioids is going to be a rarer occurrence because of this "opioid panic" BS that you can
mostly thank Purdue pharma, pill mils and Fentalogues for. Not to say that you will "like" the effect that some spend their entire lives chasing, but enough of a strong pain med will change your mind on how much they can really help.
Not to mention a whole host of other pain meds like NMDA antagonists like the arylcyclohexlamines: ketamine, PCP, Tiletamine. They can have real pain killing activity but usually send you off tripping balls vs an opioid high. Hence being labeled dissociatives.
Another one is Nitrous Oxide. Despite it's milder nature when mixed equally with o2, it's a great antinociceptive that works in the brain by utilizing the natural endogenous opioid system and descending noradrenergic system that affects the spine.
Overall I think you need far more exposure to these agents before coming to the conclusion that "your body processes pain signals differently". Hopefully you never have to find out just how much they can help, be it physical or mental pain.