Tuesday, December 25, 2007

Fentanyl Revisited

One of my most faithful readers, Elizabeth Munroz, suggested that I expand on my discussion from my last blog entry about pain management and the role of fentanyl. I think that’s an excellent idea, because this is a topic I feel very strongly about.

A computerized search of the medical literature (http://www.ncbi.nlm.nih.gov/sites/entrez/) for articles about chronic pain turned up 45,290 articles. Clearly this is a topic of intense research, and my goal here is not to write a textbook, but rather to touch on the highlights of pain management in the cancer patient, so that articles in the popular press about pain medications can be read in this context.

Acute vs. Chronic Pain

One of the points I made, and one of the concerns raised by the FDA in their recent warnings regarding fentanyl patches, is the difference between acute and chronic pain. At its simplest, the difference is obvious: acute pain happens suddenly (think of your last headache) and eventually goes away, while chronic pain lasts a long time (like someone with a bad back, whose back hurts every single day). But upon a closer look, these differences become less distinct. Someone with a bad back might have pain every day, but if they try to lift something heavy, that can send a sharp spasm of significantly increased pain shooting through them. Is that acute pain? Actually, for people who have pain every day, we usually think in terms of chronic pain with acute exacerbations. This acute jolt of pain takes place on the background of the daily pain… an important distinction for treatment.

Different Types of Pain

Pain can not only be acute or chronic, but there are different types, one of the most important being neuropathic. Imagine the pain that comes from bumping into a bruise on your thigh. Now imagine the pain that you feel when your leg has “fallen asleep.” The first of these is what pain management doctors call “nociceptive pain” and arises from tissue damage or inflammation, and the second is “neuropathic pain” and arises from damage to a nerve. Biologists have learned that these different types of pain are transmitted through different types of nerves and using different molecular mechanisms. Doctors have learned that these biological differences mean that the management of these different types of pains requires different strategies.

How do we feel pain?

There actually is no easy answer to this seemingly simple question. However, scientists do understand to some extent. When there is damage to tissue (such as from trauma or inflammation), nerves sense this damage, fire a signal to the brain, and the brain interprets this signal as pain. There are proteins in the brain called opiate receptors. These proteins help determine how active certain nerves are – the nerves that mediate the sensation of pain. Your body makes substances that attach to opiate receptors and turn down the activity of the pain-sensing nerves, decreasing the sensation of pain.

How do pain medicines work?

Opiate receptors are the targets of narcotic pain medicines, like morphine and fentanyl. The medicine attaches to the opiate receptor and turns down the activity of the nerve. Inflammation is the target of most over the counter pain medications, like ibuprofen. Less inflammation means less tissue damage, which means less activity of the nerve, and less pain. Neuropathic pain arises from damage to nerves, and medicines like neurontin help treat neuropathic pain by directly turning down the activity of the damaged nerve. These differences are very important, because the different types of pain have different causes and need different medicines to treat them.

Opiate Receptors
Courtesy of NIAAA
The figure shows how some nerves make opioids (endorphins) that send a signal to other nerves. Narcotics (exogenous opiates) mimic this signal, turning down the activity of a nerve involved in sensing pain. Naltrexone is a drug that blocks the action of opiates by blocking their ability to attach to the opiate receptor.

How are narcotics different from each other?

All narcotics work basically the same way – they attach to the opiate receptor. So what’s the difference between morphine and fentanyl? The major differences relate to how the drug is handled by the body. Fentanyl attaches much more tightly to the opiate receptors than morphine, so you need much less drug to ease the same amount of pain (in fact, fentanyl is about 100 times more potent than morphine). But fentanyl doesn’t last as long in the body. A dose of morphine can kill pain for 4-6 hours, compared to only an hour or so for a single dose of IV fentanyl. This short duration is the reason for the development of fentanyl patches… by slowly releasing the drug into the body, it can be made to last much longer. A fentanyl patch can provide pain relief for days at a time.

What about tolerance?

In an earlier article, I talked about the difference between tolerance and addiction. How does tolerance happen? Well, if the opiate receptors all have narcotic attached to them, the nerve senses this and makes more receptor. Now there are new opiate receptors that are not bound up with narcotic, and the pain comes back. With more opiate receptors on the nerve, a higher narcotic dose is needed to turn off the nerve’s activity. We call this tolerance. This happens to every chronic pain patient. They need to take more medicine to experience the same degree of pain relief. This isn’t a character flaw, and it isn’t addiction. It’s the body’s response to being treated with the drug every day.

Tolerance is exactly why fentanyl patches are meant for chronic pain and not acute pain, and why putting on a fentanyl patch for a headache can lead to an overdose. Fentanyl, being so potent, rapidly saturates the opioid receptors on the nerves of patients who don’t take these medications every day.

Pain management strategies for the chronic pain patient

So how do I treat pain in my patients? The first step is to try to determine the type of pain, so that I’m using the right drugs. If the patient has neuropathic pain, morphine won’t work as well as neurontin. If the patient has chronic pain, they need something long lasting, like a fentanyl patch or methadone. But even chronic pain patients have acute pain episodes on top of their chronic pain. For these acute pain episodes, the patient needs something that will work quickly to relieve the pain fast, but won’t last too long, so that when the pain is gone, so is the medication. Oxycodone is perfect for that type of pain: it starts to work in minutes and only lasts a few hours (unlike the sustained release version, oxycontin, which takes an hour to kick in and lasts for 8-12 hours).

Some final thoughts

Pain is manageable. The key to helping a cancer patient with their pain is to understand the different types of pain, why some medications work for some kinds of pain but not others, and to work hard to balance the benefits of pain medications with the side effects in order to maximize the quality of the patient’s life. Thankfully, here in the US, we have an abundance of pain medications available, and no one needs to live in pain for lack of taking pain medications (which is not the same thing as saying no one needs to live in pain, because unfortunately, we can’t relieve all pain). Fentanyl is a potent drug, but it’s the misuse of fentanyl that the FDA is warning about, not the correct use. Used properly, fentanyl is (in Elizabeth’s words) “a godsend” for patients with chronic pain. It shouldn’t be taken off the market, it should be used correctly.


outre said...

It never fails to baffle me how some folks with acute pain gets opiates prescribed while there are those with chronic pain who have trouble getting enough to control their pain...

Doctor David said...

Too many doctors are worried about creating drug addicts out of people with chronic pain. That's the usual reason given for limiting the amount of narcotics that are prescribed. I don't think we create drug addicts. We create people with dependency, but dependency is a physiologic response to being treated with these drugs and is not the same as addiction at all. Better to be pain free and dependent than to live with pain every day of your life.

Christian Sinclair, MD said...

Excellent review of pain control. Thanks for writing it. Wanted to encourage you to try to use 'opioids' instead of the word 'narcotics,' since narcotics tends to have a stigma ans is more associated with legal/criminal language and not commonly used in the pain literature more recently. Opioids are a class of medications, narcotics from a legal standpoint can include cocaine, and other street drugs that will clearly not put you to sleep as the name narcotic presumes.

Keep up the good work! We cover some pediatric palliative issues at Pallimed you may be interested in as well.

Doctor David said...

Hi Dr. Sinclair,

Thank you for your kind words. You're right, opioid would be a better term for me to have used than narcotic. Thanks, also, for bringing Pallimed to my attention. I'm looking forward to reading it. Sadly, palliative care is a large part of what I do, and getting better at it can only improve the care I give my patients.

Galadrial said...

I just found this post this morning.

Honestly, I find the line between "chronic" and "acute" pain to be moot. I've had spinal surgery twice...and between a dizzying array of therapy and "pain control procedures" that I had to endure to "exhaust the conservative methods first".

Doctors who were worried about "creating addicts" thought nothing about offering me Anti-depressants, which I found baffling. Since the pain was of along standing (Two accidents in a decade) it was chronic, subject to bouts of more acute pain in between. It wasn't going away.

The docs who offered the AD's were less than forthcoming about the effects...including that once I took them, I might be on them THE REST OF MY LIFE...and I saw little difference between that and the risk of addiction.

A close family member tried AD's to cope with post divorce depression, supposedly short term. That was 8 YEARS ago, and every attempt to come off them has failed. So I was not inclined to start.

I've used Fentynyl, Skelaxin, Lyrica, and even Hydrodocone, and Oxycontin with varying degrees of success. After my pain specialist suggested a second radio-frequency razotimy (when the first one failed miserably) I just gave up completely.

I stopped taking everything...all at once. I know...not suggested. BUT...not a single sign of withdrawal. My pain levels still exist, I am far from comfortable. But I also stopped feeling like a lab rat, so my specialist could feel virtuous about not "getting me hooked on meds".

I've had to accept a reduced style of life...but i could not bear another "procedure", nor feeling like a failure because I did not "get better" from a permanent injury.

Anonymous said...

be very careful with fentanyl patchs with children,I noticed they only lasted a maximum of 56 hrs. on me and a child would not be able to conve that to you, as a doctor or a parent.

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Doralda said...

I have had 5 hip replacements on the same side and suffer from constant pain, near the site where the large cage devise was inserted. Will a pain patch help. I'm unable to sit more 15 minutes at a time. PT has not seemed to help. Then broke the leg on the same side recently. So more pain