A way around opioids: Target the type of pain for better pain relief

In the old days, pain was pain, and there was not a lot of differentiating on the best way to treat it. Then came along powerful morphine in the late 1800s^[1], and more than a century later, powerful opioid painkillers^[2]. Marketing by opioid manufacturers led many people to believe, several lawsuits claim^[3], that there were few downsides to using powerful opioids to treat pain. Well, we know differently now.

At the same time we saw the rise of deaths due to opioids^[4] in the past decade, research revealed the nuances of pain. A modern medical approach, emphasized even more in the wake of new Centers for Disease Control and Prevention recommendations^[5] on prescribing opioids for pain, is to consider non-opioid painkillers first.

As a physician and pain researcher, I can say this is not as easy as it sounds, because there are different kinds of pain and because people experience pain differently. As a pain specialist, I’ve learned to use a broad array of treatments, including dozens of non-opioid pain medications, to treat the type of pain my patients describe and what I diagnose. Now, we need every clinician to practice this way, and to do so, we need to start at the beginning. An essential part of treating pain is to first identify what type of pain a person is having and then use a targeted treatment.

Three broad categories of pain

Broadly speaking, the medical community now knows there are three types of pain: nociceptive^[6] pain, neuropathic^[7] pain and inflammatory pain^[8].

Nociceptive pain is experienced when pain receptors, called nociceptors, are activated. For example, go ahead and pinch your skin right now. The pain happens because pressure receptors are being activated on nerves, and pain signals travel quickly to your brain. Some pain nerves have these special receptors, and others have bare nerve endings that can be activated by pressure, stretch, extreme temperature, chemicals or movement. The activated nerve endings send pain signals to the spinal cord and up to the brain. Nociceptive pain is a normal response to insult or injury because it tells the person to protect themselves from further injury.

Nociceptive pain can be divided into two types – somatic^[10], with receptors that monitor the musculoskeletal system, or visceral^[11], with receptors that exist in the lining of intestines. Somatic nociceptive pain results from a broken arm, for example. If a person holds really still and doesn’t move the arm, the pain is not intense. But if a person moves, all the somatic nerve receptors in the bone and muscle are activated and pain is severe.

A stomach ulcer is an example of visceral pain. If the stomach and intestines are quiet, there may be little or no pain, but as soon as the stomach and intestines start moving, the pain receptors around the ulcer are activated and severe sharp, burning pain is felt.

Neuropathic pain is felt when nerve fibers are damaged or malfunctioning. A classic example is diabetic peripheral neuropathy^[12], where patients with diabetes feel like pins and needles are stabbing them in their fingers and toes. That is because nerves have been damaged by high levels of sugar. Think of it like a fallen electric power line that has lost its insulation and is now sparking and zapping randomly on the ground. Those random zaps are injured nerves spontaneously firing and sending false signals to the brain that there is something causing pain. Neuropathic pain is pathologic pain^[13], which means that it is considered abnormal. It is not a protective response, as is nociceptive pain; it is a malfunction.

Inflammatory pain is caused by inflammation, the body’s response to injury or infection. In inflammatory diseases, such as infection, traumatic injury, burns, cuts, arthritis, inflammatory bowel disease or autoimmune diseases, the region around the nerve is inflamed. There, an inflammatory soup of pain signal molecules, such as TGN-alpha^[14], IL-1, IL-6 and ATP, lower the threshold for nerve firing, so even the slightest thing sets them off. Inflammation causes nerves to signal pain much easier than they otherwise would.

It makes sense to use pain medicines if the pain is severe, in all three types. If it isn’t really that bad, then non-medicine treatments are better. Elevate your leg, stretch your muscles, put ice on that charley horse. All that works well. Often, movement^[15], coping strategies^[16], and time for the body to heal are truly the best remedy.

If medication is needed, there are medications geared for each type.

Different pain, different treatment

Let’s look again at the example of the broken arm. If you don’t move it, it doesn’t hurt as much because the pain receptors are not being activated. So protect the arm, stabilize it, and get it fixed. Treat nociceptive pain by looking for the cause and treating the cause. If you stop the cause, the acute pain will resolve. So, immobilize the arm, realign the bone in surgery, and put a cast on it until it heals. In many instances, no pain medicine is needed. But it’s okay to use medicine for moderate and severe pain. Medications in this case can help you tolerate the fix and speed up rehabilitation and recovery.

Severe nociceptive pain can be controlled by starting with non-opioids and adding other medications as needed. Don’t stop the non-opioid pain medicines. You may think they weren’t working because the pain was too severe, but when used in combination with opioids, medicines like Tylenol and ibuprofen are what we doctors call opioid-sparing. This means that if a person needs more than Tylenol or ibuprofen, a smaller amount of opioid will be needed to control the pain if opioids are combined with non-opioids. This significantly lowers the risk of using opioids.

Nerve pain caused by damaged nerves is targeted by nerve pain medicines. Gabapentin^[17] is probably the most common, but again, there are several options. Finding the one that works best with the fewest side effects for an individual person is the key.

Inflammatory pain best responds to drugs called anti-inflammatories. There are non-steroidal anti-inflammatory drugs (NSAIDs), and steroids used to treat inflammation and reduce inflammatory pain. Aspirin, ibuprofen and naproxen are NSAIDs. Steroids, such as cortisone, have side effects of their own.

Many of these drugs were not originally developed to treat pain, so they are used by doctors “off-label^[18]” because doctors and other clinicians noticed that they were beneficial for targeted pain treatment.

For example, gabapentin’s traditional use is to stop seizures^[19]. If I prescribe it for pain, I explain it like this: Gabapentin can be used at really high doses, and is strong enough to prevent a seizure. I compare that dose to a very high volume, like listening to music so loud it might give you a headache. On the other hand, a low dose of gabapentin, like playing a stereo quietly in the background so the music is barely noticeable, calms overexcited nerves. This is how I and others use it to treat diabetic neuropathy, sciatica^[20] and even nerves injured from normal surgery.

All of this may seem complicated, and brings up many good questions that providers and patients have. Let me respond to the questions with a series of answers.

Can all three pain types occur together?

Yes, people can have only one pain type or all three pain types at the same time. After surgery, a patient will have nociceptive, neuropathic and inflammatory pain. So in this case, using a combination of medications is more effective and safer than trying to treat all the pain types with one drug.

This means that a person with all three types of pain may take multiple medicines to most effectively treat it all. Low doses of combinations of medications are often more effective and safer. This is why when drugs become generic, they often are combined into combo pills for the best effect. This is known as synergism. But, this also means that if a person only has one type of pain, a single targeted prescription may be all they need.

Are opioids still good medicines to use?

Yes, targeted pain treatment with non-opioid pain medicines may not be enough, and some patients will still need opioids. The severity of pain may be overwhelming, and opioids indiscriminately block pain sensation. Opioids are still an indispensable tool in the doctor’s toolkit for many diseases.

Are newer pain medicines being developed?

Yes, because of the opioid crisis, alternative options that are safer and have fewer side effects are appropriately being sought out. Many old drugs are being revived, reformulated and re-evaluated with new research methods. While researchers discover new benefits of ketamine^[22] and its cousin memantine^[23] for treatment of depression and memory loss respectively, each is finding resurgent use for treatment of pain.

Does marijuana treat pain?

Yes, marijuana can treat pain. The active ingredients in marijuana are similar to fat molecules our own body makes, called endocannabinoids^[25]. Endocannabinoids are retrograde messengers, meaning they travel backwards from one nerve to the nerve upstream to turn it off. But, turning off nerves indiscriminately can have some pretty horrible side effects, so researchers are trying to identify exactly which cannabinoids work best in specific body areas and for specific disease types. Once we have better research data, using marijuana-like molecules may become a targeted pain treatment.

Today, in this decade, targeted pain treatment is modern medical practice. I believe future decades will look different, as newer medicines are developed and non-medicine options are emphasized. Already, even major surgeries are being done using targeted pain treatment with improved pain control^[26] and with safer outcomes^[27]. Non-medicine pain control options coupled with targeted pain medicine treatments when needed, is what the doctor should be ordering today.

References

1. ^{^} powerful morphine in the late 1800s (www.history.com)
2. ^{^} powerful opioid painkillers (www.drugabuse.gov)
3. ^{^} several lawsuits claim (fortune.com)
4. ^{^} rise of deaths due to opioids (www.drugabuse.gov)
5. ^{^} Centers for Disease Control and Prevention recommendations (www.cdc.gov)
6. ^{^} nociceptive (www.healthline.com)
7. ^{^} neuropathic (www.theacpa.org)
8. ^{^} inflammatory pain (www.ncbi.nlm.nih.gov)
9. ^{^} PRESSLAB/Shutterstock.com (www.shutterstock.com)
10. ^{^} somatic (www.ncbi.nlm.nih.gov)
11. ^{^} visceral (www.ncbi.nlm.nih.gov)
12. ^{^} diabetic peripheral neuropathy (www.niddk.nih.gov)
13. ^{^} pathologic pain (link.springer.com)
14. ^{^} TGN-alpha (www.pnas.org)
15. ^{^} movement (www.ncbi.nlm.nih.gov)
16. ^{^} coping strategies (www.ncbi.nlm.nih.gov)
17. ^{^} Gabapentin (www.medicinenet.com)
18. ^{^} off-label (www.fda.gov)
19. ^{^} stop seizures (www.medicinenet.com)
20. ^{^} sciatica (www.mayoclinic.org)
21. ^{^} gpointstudio/Shutterstock.com (www.shutterstock.com)
22. ^{^} ketamine (www.ncbi.nlm.nih.gov)
23. ^{^} memantine (www.ncbi.nlm.nih.gov)
24. ^{^} BestStockFoto/Shutterstock.com (www.shutterstock.com)
25. ^{^} endocannabinoids (emedicine.medscape.com)
26. ^{^} improved pain control (www.ncbi.nlm.nih.gov)
27. ^{^} safer outcomes (www.ncbi.nlm.nih.gov)