What are the similarities between chronic pain and opioid addiction?

By Henriette Poulsen, M.D and Kim Kristiansen, M.D.

Addiction in its worst form is to want a substance so badly that family, friends, work, future, health and not even your own survival matter. A terrible craving where getting the drug is all that is important. Why risk prescribing opioids at all when this might be the consequence? And who in their right mind would risk taking such a drug?

But what if each day was a constant struggle against pain in which it seemed easier to die than to face another sunrise? What if you already lost your job due to chronic pain? What if your  friends had all gone and you  didn’t even have the energy to care properly for your children? Because all you could think about was the throbbing, burning or stabbing pain that wouldn’t even let you sleep.

The term preferred to describe addiction by psychiatrists is substance dependence, which is defined in the internationally used ICD-10¹ (published by the World Health Organization) and DSM-IV² (published by the American Psychiatric Association) diagnostic systems respectively. These can be viewed by following the links below. In both systems the presence of physical withdrawal symptoms and tolerance – i.e. that increased doses of the substance are required to achieve effects originally produced by lower doses – is emphasized.

Opioids are potent pain relievers and sometimes they are part of the treatment used to alleviate severe chronic pain.  Sometimes patients need more and more of the drug to relieve the pain.  And most pain patients treated with opioids for a longer period do develop the terrible and frightening symptoms of physical withdrawal if the treatment is suddenly stopped.

Is it fair to call patients, who don’t feel they can live without opioids for the management of pain, addicts?

Some patients with chronic kidney disease tend to need an increasing amount of diuretics as their disease progress. And a sudden stop leads to massive fluid retention. If the prescription of diuretics suddenly was limited – is it hard to imagine that  patients facing a frightening breathlessness would try every way possible to get their hands on more diuretics? And yet we would never describe a patient with chronic kidney disease as “addicted” to diuretics.

Opioids are different. Because they have other effects than that of relieving pain. They are able to stimulate the brains “reward circuits”. These are found within the mesocorticolimbic system and mediate the release of dopamine in several areas of the brain³. The result is a feeling of “high”, euphoria, inner peace or easing of negative thoughts. The stimulation of this system may also relieve the symptoms of depression and anxiety as both are more prevalent in patients with non-medical prescription opioids use⁴. Depression and other mood disorders often co-exist with chronic pain⁵.  Not everyone experience the psychoactive properties of the opioids to the same extent. However in some the feeling stimulates continued use by the means of positive reinforcement coupled with the negative reinforcement effects of physical withdrawal symptoms and anhedonia – an extensive feeling of unpleasantness experienced when opioids are not in the body³.

The pain relieving as well as the psychoactive properties of the opioids have been known for centuries. In their natural form different types of opioids are more or less refined alkaloids of poppy seeds. One of the earliest distributed forms was opium which contains several different alkaloids. Opium was used in pain relieving and soothing mixtures in the 19^th century.

In the August 1867 edition of Harper’s Magazine, Fitz Hugh Ludlow writes about a patient who is an “opium-eater”⁶ – a man in his forties who started using an opium mixture called M’Munn to relieve the pain of a corneal inflammation. The social, emotional and physical collapse of a man addicted to opium and the pain of withdrawal is eloquently described in a 19^th century setting.

While initially using the opium mixture to treat his eye pain he discovers the other effects: “…he had resort to M’Munn, in ounce doses, whenever the world went wrong with him. If he had a headache or a toothache; if the weather depressed him, if he had a certain “stint” of work to do without the sense of native vigor to accomplish it; if he was perplexed and wished to clear his head of passion; if anxieties kept him awake; if irregularities disturbed his digestion – he had always on refuge certain. No fateful contingency could pursue him inside M’Munn’s enchanted circle.”

Using opioid for other reasons than treating pain is termed misuse. And this also happens in modern pain management. It is a slippery slope if a patient starts treating sleep problems, anxiety symptoms or symptoms of depression with opioids. Because when stimulating the “reward-system” repeatedly to achieve a “high” or “calm” there is a risk of developing not only increased psychological pain between doses  - as described above – but also long term craving – a  compulsive drug-seeking behaviour which persists years after the physical withdrawal symptoms and immediate anhedonia have subsided³. This is also vividly described by Ludlow⁶:

“When by the physician’s order he abandoned “M’Munn” on the subsidence of the eye-difficulty, his symptoms were uneasy rather than distressing, and disappeared after a few days’ oppression at the pit of the stomach and a few nights’ troubled dreaming. But he had not forgotten the sweet dissolving views at midnight, the great executive achievements at noonday, the heavenly sense of a self-reliance which dare go any where, say any thing, attempt anything in the world. He had not forgotten the nonchalance under slight, the serenity in pain, the apathy to sorrow, which for one month set him as calm as Boodh in the temple-splendors of his darkened room. He had not forgotten that the only perfect peace he had ever experienced was there, and he remembered that peace as something which seemed to blend all assuaged passion and confirmed dignity of old age with that  energy of high emprise which thrills the nerves of manhood.”

Today the phenomenon of long term craving is proposed to be caused by a combination of changes of the reward system’s allostasis and a conditioning response stimulating a change of the brains structure and the strength of synapses³. The former results in a new stable “set point” of this outside the normal homeostatic range – a constant stimulation is needed for the person just to feel “normal”. The latter involves plasticity of neurons in the areas of the brain involved with learned behaviour, memory and emotion. This is thought to be the reason why craving suddenly can be stimulated by seeing objects or persons associated with taking the drug. The feeling of craving often intensifies during periods of stress and worrying.

The strong, uncontrollable craving is an essential part of drug dependence.  The DSM-IV and ICD-10 diagnostic systems defines a behaviour in which loss of control makes drug seeking the top priority in life resulting in progressive neglect of alternative pleasures or interests, failure to fulfil major obligations at work, school or home and problems regarding legal, health, social and interpersonal matters.

The chronic pain patient who is asking for more opioids to relieve pain may easily be misunderstood and suspected of having drug dependence according to the ICD-10 /DSM-IV diagnostic criteria – especially because tolerance and physical withdrawal symptoms are included in the definitions. The clinical implications are challenging and  using these definitions could easily bias the results of research projects and epidemiologic studies examining addiction.

Thus, in 2001 a consensus definition of addiction was produced by a Liaison Committee on Pain and Addiction consisting of three major American organisations involved in pain and addiction management⁷: Addiction is a primary, chronic, neurobiologic disease, with genetic, psychosocial, and environmental factors influencing its development and manifestations. It is characterized by behaviors that include one or more of the following: impaired control over drug use, compulsive use, continued use despite harm and craving. In this definition addiction is completely separated from tolerance and physical withdrawal. The complex aetiology is underscored and the exact behaviours which characterize an addict are further emphasized.

The many factors involved in the development of addiction also means that one person with prolonged use of opioids might develop addictive behaviour on cessation of the treatment – whereas another might not. One might miss the comfort of the rewarding properties of the opioids without losing control – and another might steal or buy drugs illegally to alleviate the craving – and yet another might buy drugs illegally to alleviate undertreated pain. Even misuse of the opioids to treat symptoms of anxiety, sleep problems etc doesn’t fully predict later addictive behaviour.

But once more, it must be emphasized that drug seeking behaviour, signs of misuse and an increased need of opioids – collectively called aberrant drug behaviour – can have many different reasons: From progression in an underlying disease and depression to addiction or even diversion of the prescribed drugs. Fortunately physicians are not limited to watching the behaviours of patients – patients and carers can discuss these issues.

In order to navigate in this complex we (both healthcare professionals and patients) must be aware of these problems, talk about them openly and routinely and if signs of aberrant drug behaviour occur investigate the cause and act according to findings. Another important fact is that chronic pain is a dynamic and fluctuating condition why this must be an ongoing strategy.

The next blog post will take a close and practical look at this, and at tolerance, addiction and pseudo-addiction.

1. World Health Organization: The ICD-10 Classification of Mental and Behavioural Disorders: Clinical descriptions and diagnostic guidelines: F10-F19: Mental and behavioural disorders due to psychoactive substance use. Geneva, Switzerland, 1992. http://www.who.int/substance_abuse/terminology/ICD10ClinicalDiagnosis.pdf
2. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders 4^th ed. Washington DC: American Psychiatric Association 1994. Can be viewed at allpsych.com: http://allpsych.com/disorders/substance/substancedependence.html
3. Ballantyne JC et al: Opioid dependence and addiction during opioids treatment of chronic pain. Pain 129 (2007) 235-255 http://www.painjournalonline.com/article/S0304-3959(07)00161-3/abstract
4. Martins SS et al: Mood and anxiety disorders and their association with non-medical prescription opioid use and prescription opioid-use disorder: longitudinal evidence from the National Epidemiologic Study on Alcohol and Related Conditions. Psychological Medicine (2011) 1-12
5. Agüera-Ortiz et al: Pain as a symptom of depression: Prevalence and clinical correlates in patients attending psychiatric clinics. Journal of Affective Disorders (2010) 130 (1-2) 106-12
6. Ludlow FH: What shall they do to be saved? Harper’s Magazine August 1867: 377-387 http://harpers.org/archive/1867/08
7. Savage SR et al: Definitions Related to the Medical Use of Opioids: Evolution Towards Universal Agreement. Journal of Pain and Symptom Management. (2003) 26 (1) 655-67

Henriette Poulsen, M.D. and Kim Kristiansen, M.D. (2011). What are the similarities between chronic pain and opioid addiction? Picture of Pain Blog : http://blog.dolotest.com/?p=830