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Why One Pain Drug Works for You and Another Doesn't

Pain management is highly personal, this doctor says

By Val Jones, M.D.

(This article appeared previously on

Most of my patients think about pain medicines in terms of the symptoms they treat. “This is my headache medicine, and this is my arthritis medicine,” they often say. Health care providers are more likely to categorize pain medicines by the way they work: some are anti-inflammatory, some affect nerve endings and others influence how the brain perceives pain.

But the truth is that no matter how you classify pain medicines, there is no way to know if they’ll help until you try them for yourself.

Most people don’t realize that pain management is personal. Research is beginning to help us understand why people respond to medicines so differently, and one day we will probably be able to personalize treatment plans more successfully.

It's All in the Genes

For now, there are several known genetic reasons why pain medicines are more or less effective for one individual over another. Genes affect:

  • The number of enzymes that break down medicines and remove them from the body  Some people have larger numbers of these enzymes and therefore require more of the drug to feel its pain-relieving effects. Others may be strongly affected by even small doses of drug.
  • Pain medicine receptors, variations of which can make one medicine effective and another (nearly identical medicine) ineffective in relieving pain
  • Differences in carrier molecules that transport pain medicine across the blood stream and into the cells that are triggering pain sensations  Some people have fewer carrier molecules to bring the medicine to the site of pain.
  • The number of “middle man” neurotransmitter molecules that pass along the pain response  Too many of these molecules can reduce drug binding and mute the pain-relief effects of some drugs.

When pain is severe, prescription medications may be necessary. However, mild to moderate pain may be effectively managed with over-the-counter (OTC) medicines. I believe in the "start low, go slow" approach to finding the smallest effective dose of pain medicines. I always recommend that my patients read and follow all the instructions on the Drug Facts labels to make sure they don’t accidentally overdose on active ingredients.

Consider Side Effects

When I choose a pain reliever with my patients, the first thing I think about is potential side effects. Some medicines (such as non-steroidal anti-inflammatory drugs like ibuprofen, sold as brands including Advil and Motrin, and naproxen sodium, such as Aleve) can be hard on the stomach lining, or cause bleeding in people who are at risk for it. Other medicines (such as acetaminophen, like Tylenol) can harm the liver if used in excess, while prescription pain medicines can cause constipation and drowsiness. The best pain medicine to start with is one that is least likely to cause harm to the specific person.

The next thing I ask is whether the medicine has worked for the patient in the past. Previous experience is one of the best indicators of future success. Since I know that my patient has a unique, genetically determined number of enzymes, transporters and receptors, previous experience with pain medicines will give me a good idea of how well he or she will tolerate it again, and if it will be effective.

Different Meds for Different Needs


Finally, I consider the type of pain that the patient is experiencing. If the pain is caused by inflammation (from an injury, surgery, or arthritis) I’ll consider a medicine with primarily anti-inflammatory properties. If the pain is caused by tension (such has headache) or complicated by fever, I may consider acetaminophen first.

If the pain is coming from a nerve (such as sciatica or neuropathy), then I’ll use pain medicines that work for nerve pain specifically. If the pain is complicated by depression, I may discuss additional medicines and approaches.

Sometimes, combinations of medicines are significantly more effective than one medicine alone at treating pain; this is why some prescription pain relievers are combinations of an opioid and acetaminophen.

When using more than one pain relief medicine, it is important to compare active ingredients in both prescription medications and OTC products to make sure that accidental overdoses do not occur. I also recommend consulting with a health care professional if there are concerns about drug interactions or if the patient is already on a significant number of prescription medications that could interact with his or her OTC pain medicine choices.

More to Learn

The bottom line is that science is still catching up to pain management. Perhaps one day a simple blood test will help us to determine the very best pain medicine regimen for a specific patient at a given time. But until then, adopting a strategy of careful trial and error (avoiding unwanted side effects, using the lowest effective doses, and consulting a physician when pain is severe) is the only option.

Don’t worry too much about whether a specific medicine is “best” for your pain. Pain management is very personal, so you will need to discover your own best solution.

(Disclosure: Dr. Val Jones is a paid consultant for McNeil Consumer Healthcare Division.)

Val Jones, M.D., is an award-winning writer and graduate of Columbia University College of Physicians and Surgeons. She is board certified in Physical Medicine and Rehabilitation and serves as a traveling physician to hospitals in 14 states. She shares her thoughts about healthcare on her blog at Read More
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