by Jason Schexnayder, PT, DPT, CMTPT

What are Opioids?

Opioids are drugs that are derived from the poppy plant or that are synthetically created to mimic the chemical structure of the poppy plant. They treat acute and chronic pain symptoms for various conditions. They bind to receptors throughout the body, manipulate the pain and pleasure experience, and cause the release of dopamine.

Common opioids include:

  • Hydrocodone (Vicodin®)
  • Oxycodone (OxyContin®, Percocet®)
  • Oxymorphone (Opana®)
  • Morphine (Kadian®, Avinza®)
  • Codeine
  • Fentanyl
  • Remifentanil
  • Heroin

What’s the problem?

Unfortunately, because opioids not only tend to reduce pain but also cause euphoria, these drugs tend to be highly addictive. In the United States in 2012, opioids were prescribed over 259 MILLION times.1 This is partly because over 100 MILLION Americans suffer from some form of chronic pain with over 25 MILLION experiencing “moderate to severe, debilitating pain”.1

Compared to other countries, the US seems to have higher rates of pain. For instance, the US averages 33% of chronic pain states where other countries average between 13 – 19%.1  Also, chronic pain conditions cost the US anywhere between $560 – $635 BILLION A YEAR1🥴🤢🤮. Finally, these drugs also cause a litany of side effects, some of which you may have never heard of.

Common Side Effects

On top of addiction and euphoria, other side effects include:

  • Drowsiness
  • Confusion
  • Nausea
  • Constipation
  • Respiratory Depression
  • Drug Dependence and/or Addiction
  • In pregnant women, opioid use can cause a litany of dangerous side effects for you and your baby. 

Let’s talk a little more about constipation, respiratory depression, and addiction.

  • Constipation

    • I don’t think I need to explain what constipation entails. However, the problems constipation can cause are not as well known. Constipation lasting several days, a very common side effect when taking opioids, can lead to a number of issues. 
      • Non-traumatic low back pain
      • Hiatal Hernia – in this instance, this is due to straining. This occurs when a portion of the stomach protrudes through the diaphragm. This can be dangerous over time as this increases your risk for multiple diseases, including esophageal cancer, one of the deadliest known cancers.
      • Hemorrhoids
      • Anal Fissure…this is painful just to say
      • Fecal Impaction…this can potentially cause death
      • Rectal Prolapse
    • Each of these potential complications can also have its own complications…oh yay 😑

  • Respiratory Depression, also known as Hypoventilation

    • You take fewer breaths per minute and breathing isn’t efficient…that’s the gist of it. This can cause a lack of oxygen (hypoxia) to the body and acidosis due to an inability to expel enough carbon dioxide from the lungs. Unfortunately, respiratory depression occurs more often than once thought, even in opioid-tolerant patients.2 This increases your risk of developing cancer, other respiratory diseases, and could progress badly enough to cause death.
  • Drug Dependence/Addiction

    • Opioid addiction, and opioid prescription in general, has become a worldwide problem. What’s concerning about this being a continual, and growing, worldwide problem is that the more we study these drugs, the more it becomes clear we need to find better ways to manage pain.
    • According to the CDC, in 2018, nearly 70% of almost 68,000 overdose deaths involved an opioid.3 And, 50 – 80% of fatal opioid overdoses occurred in patients who were on an opioid regiment.1 Basically, this means that these people were familiar with taking opioids and still died from taking them.

The Unheard-Of Side Effect…

Opioid-Induced Hyperalgesia

What a mouthful…

Opioid-induced hyperalgesia (OIH) is a state of INCREASED sensitivity to painful stimuli as a result of taking opioids without signs of disease progression or withdrawal.2,5 This means that despite taking a drug that’s supposed to reduce your pain, it’s actually increasing it. Now, there’s a difference between opioid tolerance and OIH.

Tolerance is defined as the need for an increase in opioid dose in order to receive the same type of pain relief.2 There are many similarities between tolerance and OIH, which makes it difficult to differentiate clinically. However, one of the main differences would be that a person who is tolerant would have a DECREASE in pain with an increased opioid dose whereas someone with OIH would likely experience an INCREASE in pain with an increase in opioid dosage.

Despite previous beliefs, we know that tolerance may occur within hours of taking opioids for the first time and we suspect this might also be true for OIH.2 So, these aren’t necessarily side effects that only occur in people who have taken and/or continue to take opioids.

But How?

OIH is a multi-factorial condition with several theories on why it occurs. None of these mechanisms or theories have been proven yet. Due to this, the study of OIH gets extremely complicated, involving a bunch of pain pathways, receptors, cellular components, etc. I’m going to spare you the time and confusion and keep this simple.

It’s expected that changes in the nervous system, central (brain and spinal cord) and peripheral (nerves and receptors outside of the brain and spinal cord), are the culprits of OIH.4 Another theory says that because your body’s natural equilibrium (homeostasis) is altered by using a drug to reduce pain, your body, in turn, responds by creating a state of increased pain to restore equilibrium1…well, isn’t that convenient 🤦🏼‍♂️.

Studies show that chronic opioid use leads to an increased release of excitatory compounds in the spinal cord.4 Microglia are also activated in response to opioid use and they cause the release of cytokines (you should recognize cytokines from our blog on obesity).1 Cytokines are pro-inflammatory cells that increase neural activation. Due to the increase of these excitatory and pro-inflammatory compounds, this could create a state of neurological inflammation, increasing the number of pain signals sent to the brain.1

As you can see, OIH likely works in multiple ways, all of which we don’t quite understand yet.

Examples of OIH

187 community-dwelling adults with CHRONIC pain were studied. 85 were CURRENTLY USING opioids and 102 weren’t. The researchers used multiple parameters to test each individual’s pain experience, including heat sensitivity. It was found that the individuals on an opioid regiment experienced more pain than the group that wasn’t taking the drugs.6

50 patients were to undergo major abdominal surgery. They were randomly assigned into 2 groups:  one that would receive a HIGHER opioid dose during surgery and the other group wouldn’t. The group that received the higher dose reported significantly higher pain symptoms after surgery (i.e. hyperalgesia) than the group receiving the lower dose.7 This shows that OIH likely develops uniquely with different drugs, at different doses, and in different situations. As I said, it’s a complicated side effect.

355 patients, on a steady opioid regimen, were scheduled for a surgical procedure. Each group received a standardized injection prior to their procedure. Both before and after the injection, patients were asked to rate their pain and unpleasantness from 0 – 10. Compared to a control group, the study groups reported higher pain and unpleasantness levels before (resting pain) and after the SAME painful stimulus (the injection). Also, the dosage and time spent taking opioids were directly correlated with increasing pain and unpleasant reports.8 This means that the longer someone took an opioid and the higher the dosage, the more likely they were to rate that SAME stimulus as more painful than the other groups.

Final Notes

As usual, the purpose of this blog is to provide you with information. That way you can make better decisions in regard to your health.

Unfortunately, many factors affect pain, which makes it difficult to manage. If it were easy to manage, then the “opioid epidemic” wouldn’t be a worldwide problem. If physical injuries or acute illnesses were the only things that caused pain, then after you physically healed from an injury or recovered from an illness, your pain would subside. Sadly, that’s not how the human body works.

The question is…are opioids worth the risk? In certain situations, of course. Opioids are effective at reducing pain. However, as you’ve learned, they come with a lot of side effects and risks. When it comes to medication, you should ALWAYS discuss things with your doctor FIRST.

Do you have side effects? Talk to your doctor. Want to increase or decrease your dosage? Talk to your doctor. Concerned about your health in regard to your medication? Talk to your doctor. Taking medication and want to change your diet, start exercising, or change your both? Talk to your doctor. Pregnant or trying to get pregnant? Please, talk to your…

You get the point.


  • Discuss treatment options other than opioids
  • If you’re experiencing side effects and are on opioids, ask about a change to your opioid regimen, tapering, etc.
  • NEVER stop taking your prescribed medication cold turkey…talk to your doctor FIRST
  • If taking multiple medications, ask your doctor about drug interactions
  • Ask questions and lots of them
    • It’s NEVER a bad idea to ask questions to understand your options and determine what’s best for YOU!
  • Chronic pain? Meditation, positive affirmations, psychological counseling, etc. all can improve your symptoms
  • Pain or no pain, drugs or no drugs, a healthy diet and regular, moderate to high-intensity exercise can drastically improve your life…

Story Time…

I’ve treated Rachelle for several months now. In one of Rachelle’s sessions, we spent a considerable amount of time talking about her anxiety, attitudes towards her condition, her medications, the possibility of OIH, and other aspects of her life. I don’t know if Rachelle had OIH or simply developed a tolerance. My knowledge and experience are limited in regard to medication and OIH to know that definitively. Regardless of what it was, medication, attitude, lifestyle, etc. clearly impacted Rachelle’s life and pain experience.

Addressing these things is one of the most over-looked but important aspects of our jobs as therapists. I’m so proud of Rachelle’s progress and turnaround that I’d like her to be the one to share her story…so without further adieu, here’s Rachelle…

“I’m a 38-year-old woman…

and for as long as I can remember I have had neck pain from an injury that occurred at birth. However, it was not until my teens before I saw a specialist and discovered the problem. I was in my twenties and thirties before the pain began to really affect my life. Our health is something we so often take for granted until it’s gone. But despite the discomfort, I grew up strong and healthy. No one really knew I was hurting and I just dealt with it.

After a wreck in my college years, an MRI showed I had osteoarthritis in my neck. It was quite advanced for my age. At this point, my doctor started me on muscle relaxers to treat the symptoms. Years later, I was in a series of car accidents that left me with a bulging disc in my cervical spine, which led to chronic pain, migraines, and a number of other issues. The list of specialists grew and I began to see one health problem after another.

In addition to the muscle relaxer,…

I was also put on non-narcotic pain medication. I took that daily for six years and then switched to opioid pain medication. The dosage increased over time. As the years went by, the pain grew worse and spread. I was diagnosed with Fibromyalgia and hurt everywhere; far worse than I could have ever imagined. I fought this daily for 10 years. My pain stayed between 7-10 and my life slowly started to slip away at such a young age.

I was dependent on the medications to function, yet there were side effects that only created more problems and reasons to take another medication. My situation felt hopeless and I just wanted to function normally again. For a period of time, I do believe the meds helped me regain parts of my life back. However, though it wasn’t clear at the time, I know now that my health had taken a turn for the worse after becoming dependent on the daily use of opioid medication. I want to share my story with others because this is a real problem in our world today and so many of us are trapped in a cycle we’re not even aware of.

During my health struggles, I began to do some research myself, turning to books, articles, and professionals for guidance. I brought what I learned to the doctors for discussion along with any questions I had. I read about a condition called opioid-induced hyperalgesia. After reading, I realized it was very possible that the pain medication was making my situation worse.

My prayer was that this would be an answer for me, and it was!

I took 3-4 tablets a day for pain and had a pain level of 7-10. Today, I don’t take opioid medication and I’m in less pain than I ever imagined possible at this point in my life. My pain is no longer all over but in localized areas where my initial injury occurred, and my pain level stays between a 2-4. I’m also off of all other medications and only take Tylenol occasionally when needed.

Although it was not an easy process, over the last two years I have worked harder than ever getting off meds, committing myself several days a week to physical therapy and exercise, and have made changes to my diet to better my overall physical and mental health. Today, I’m 5 months pregnant with my second child, and I’m healthier and happier than I have been in years. I couldn’t have gotten here without making a decision that I was better off without all the medication, and fighting hard to get off of it. There are so many tools and resources out there, and we can learn to manage chronic pain better and live stronger, healthier lives.”

Rachelle Perdue Glover, January 2021


  1. Arout CA, Edens E, Petrakis IL, Sofuoglu M. Targeting Opioid-Induced Hyperalgesia in Clinical Treatment: Neurobiological Considerations. CNS Drugs. 2015;29(6):465-486. doi:10.1007/s40263-015-0255-x

  2. Hayhurst CJ, Durieux ME. Differential Opioid Tolerance and Opioid-induced Hyperalgesia: A Clinical Reality. Anesthesiology. 2016;124(2):483-488. doi:10.1097/ALN.0000000000000963

  3. Understanding the Epidemic. Centers for Disease Control and Prevention. Published March 19, 2020. Accessed December 28, 2020.

  4. Lee M, Silverman SM, Hansen H, Patel VB, Manchikanti L. A comprehensive review of opioid-induced hyperalgesia. Pain Physician. 2011;14(2):145-161.

  5. Brush DE. Complications of long-term opioid therapy for management of chronic pain: the paradox of opioid-induced hyperalgesia. J Med Toxicol. 2012;8(4):387-392. doi:10.1007/s13181-012-0260-0

  6. Hooten WM, Lamer TJ, Twyner C. Opioid-induced hyperalgesia in community-dwelling adults with chronic pain. Pain. 2015;156(6):1145-1152. doi:10.1097/j.pain.0000000000000170

  7. Guignard B, Bossard AE, Coste C, et al. Acute opioid tolerance: intraoperative remifentanil increases postoperative pain and morphine requirement. Anesthesiology. 2000;93(2):409-417. doi:10.1097/00000542-200008000-00019

  8. Cohen SP, Christo PJ, Wang S, et al. The effect of opioid dose and treatment duration on the perception of a painful standardized clinical stimulus. Reg Anesth Pain Med. 2008;33(3):199-206. doi:10.1016/j.rapm.2007.10.009

Unused References

  1. Eisenberg E, Suzan E, Pud D. Opioid-induced hyperalgesia (OIH): a real clinical problem or just an experimental phenomenon?. J Pain Symptom Manage. 2015;49(3):632-636. doi:10.1016/j.jpainsymman.2014.07.005

  2. Low Y, Clarke CF, Huh BK. Opioid-induced hyperalgesia: a review of epidemiology, mechanisms and management. Singapore Med J. 2012;53(5):357-360.

  3. Angst MS, Clark JD. Opioid-induced hyperalgesia: a qualitative systematic review. Anesthesiology. 2006;104(3):570-587. doi:10.1097/00000542-200603000-00025

  4. Fletcher D, Martinez V. Opioid-induced hyperalgesia in patients after surgery: a systematic review and a meta-analysis. Br J Anaesth. 2014;112(6):991-1004. doi:10.1093/bja/aeu137