The motivation to take opioids in the face of adverse consequences can be explained by several theories, one of which is termed the “opponent process” theory. Put forth by Richard Solomon and John Corbit in their 1974 paper “An opponent-process theory of motivation,” this theory arises from a balance between two valuationally opposite components — a loss of function within the reward-mediating dopaminergic circuits and an increased function of stress-related circuitry involving the extended amygdala, the kappa/dynorphin opioid and corticotrophin-signaling systems. These corticotrophin-signaling systems can become hyperactive during opioid dependence and become expressed as increased angst/anxiety and aggressive behaviors.
The second theory which attempts to describe the reasons behind motivated opioid misuse is the “incentive sensitization” theory which proposes an increase in drug-paired cues with chronic drug taking. In their paper “Pain Therapy Guided by Purpose and Perspective in Light of the Opioid Epidemic” published in Frontiers in Psychiatry, Arnie Severino and colleagues describe how the negative affective state of depression and anxiety associated with CP can be temporarily relieved by the analgesic and euphoric properties of acute opioid use which contributes to their abuse liability during the CP state. Long-term substance abusers tend to build a biochemical tolerance over a prolonged period of time. Overtime, the user tends to increase their dosage in order to achieve a higher high which can eventually lead to an overdose. However, if a long-term user has received treatment for their addiction, they are in greater danger of overdosing if they relapse.
When patients undergo opioid withdrawal and excessive tapering, they may experience symptoms such as diarrhea, vomiting, agitation, hyperalgesia (increased pain), hyperthermia and hypertension. This can be further accompanied with feelings of depression and anxiety. Due to the aversive nature of the aforementioned symptoms, patients instead decide to continue using the drug, seeking a degree of pain relief and euphoria that is becoming harder and harder to obtain at higher dosages. In a paper titled “The opioid epidemic: a central role for the blood brain barrier in opioid analgesia and abuse” Charles Schaefer, Margaret Tome, and Thomas P. Davis describe how tolerance to the euphoric effects of opioids can develop quite rapidly and at an alarming rate. This can cause both therapeutic users and recreational users to become diagnosed with opioid addiction, also known as opioid use disorder.
The American Psychiatric Association defines opioid use disorder as the “compulsive, prolonged self-administration of opioid substances that are used for no legitimate medical purpose or, if another medical condition is present that requires opioid treatment, that are used in doses greatly in excess of the amount needed for that medical condition.” Due to legal concerns and overdose risk, many doctors consider stopping the delivery of opioid medication to their patients, many of whom have never misused the medication. The Centers for Disease Control and Prevention introduced guidelines that dictated a maximum allowed dosage for patients and an ethics amendment which urged doctors to avoid prescribing for CP unless death is imminent.
Even though these guidelines were voluntary, many doctors understood them as mandatory guidelines to follow. As a result, thousands of patients in the United States who have had their doses reduced or eliminated (an attempt to prevent addiction) are instead in perpetual pain and have an increased risk of suicide.
In fact, an article published in The New England Journal of Medicine by Nora Volkow and Thomas McLellan, titled “Opioid Abuse in Chronic Pain — Misconceptions and Mitigation Strategies,” have shown that less than 8 percent of people suffering with CP become addicted. The U.S. Survey on Drug Use and Health has shown that 80 percent of people who misuse opioids receive the medication from family and friends and not from legitimate pain treatment sources such as institutions, clinics, and university hospitals.
A call to action published by a unified community of medical stakeholders and key opinion leaders in the journal Pain Medicine, titled “International Stakeholder Community of Pain Experts and Leaders Call for an Urgent Action on Forced Opioid Tapering,” challenged the forced opioid tapering which has been occurring in patients receiving long-term prescription opioid therapy for CP. “Legacy patients” diagnosed with CP who have been progressively prescribed high opioid doses over many years now face additional and very serious risks of decreasing their dosage amount.
Rapid forced tapering procedures have shown to destabilize many of these legacy patients. This has resulted in severe opioid withdrawal accompanied by worsening pain and profound loss of function. In order to escape the suffering due to these withdrawal symptoms, some patients seek relief from illicit sources of opioids, whereas others may become acutely suicidal. Opioid addiction can even lead to dysregulation of the hedonic brain circuitry and the inability for the body to efficiently respond to stressors in order to regain homeostasis. This can cause those who are addicted to opioids to have difficulty regulating their everyday emotions and blunt the ability to experience very positive emotions.
The ability to attend to and regulate one´s emotional response during emotionally charged events relies on the health of a central-autonomic network (for example, medial prefrontal cortex → anterior cingulate cortex and anterior insula → central nucleus of the amygdala → hypothalamus → nucleus of the solitary tract → ventrolateral medullary) with effects upon the vagus nerve and the heart. The vagus nerve is the 10th cranial nerve of the body which sends signals back and forth from your brainstem down to the heart, the lungs, and the digestive tract. It is the main nerve of the parasympathetic nervous system and is active during times of relaxation and strongly correlated with psychophysiological wellbeing.
In order to know if the vagal nerve is active, one can look at high-frequency heart rate variability (hfHRV), which is the beat-to-beat modulation of heart rate due to the vagus nerve. Healthy individuals ranging from long-term athletes, meditators, and those who generally tend to have a more positive outlook on life and circumstances tend to exhibit high frequency HRV (typically within the range of 0.15 to 0.40 Hz) while those with anxiety, depression, and certain CP conditions display low HRV values.
Heightened phasic HRV in response to emotionally challenging circumstances has been shown to reflect one’s ability to efficiently regulate psychophysiological wellbeing whereas individuals with difficulties in emotion regulation exhibit lower HRV at rest and blunted phasic HRV during emotion regulation tasks. Therefore, HRV can be considered a good objective indicator of how well one can regulate emotions.
A study published in the journal Psychopharmacology, titled “Deficits in Autonomic Indices of Emotion Regulation and Reward Processing Associated with Prescription Opioid Use and Misuse,” by Eric Garland and colleagues found that opioid misusers exhibit significantly less hfHRV during positive and negative emotion regulation and significantly positive affect, than nonmisusers while controlling for confounds (that is, pain severity and emotional distress).The comorbidity of CP and opioid misuse is linked with emotion dysregulation and reward processing deficits as indexed by low HRV.
These findings suggest that treatments developed to increase hfHRV through restructuring reward processing and increasing emotion regulation may be a promising avenue for successfully treating those suffering with CP, opioid misusing patients, and those on strict tapering regimens.
Motivational nondirective resonance breathing (MNRB) is a treatment which I developed which utilizes diaphragmatic breathing and open-awareness meditation to stimulate the vagus nerve (that is, hfHRV) and increase emotion regulation in those suffering from chronic widespread pain. In the spring of 2019, I will be running a randomized clinical trial where I will be comparing the treatment efficacy of MNRB with transcutaneous vagus nerve stimulation (tVNS) — a noninvasive means of electrically stimulating the vagus nerve through the left ear.
Harnessing the treatment potential of the heart, mind, and body in order to combat opioid addiction and psychophysiological suffering in those with CP is an ethical and safe means of progressing pain research and management. I believe that new studies which are integrative and innovative may contribute to the development of more treatment options that are effective and reliable.
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