To Combat the Opioid Epidemic We Need Better Ways to Manage Pain

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The rate of overdoses due to opioid addiction has become the leading cause of death for Americans under 55. A 2018 National Vital Statistics System report showed that the epidemic has killed more people than the Vietnam and Iraq wars combined. Some people are more susceptible to becoming addicted than others, yet nobody is immune.

While deaths due to opioid addiction and onset overdose are increasing, opioids are still prescribed regularly. Primary care physicians continue to treat chronic pain (CP) conditions with chronic opioid therapy despite the fact that opioids have generally failed to alleviate pain intensity and function and have shown to cause a myriad of adverse side effects.

This may be a reason as to why nearly half of those diagnosed with CP still receive inadequate pain relief, continue to suffer from a wide variety of psycho-social issues, and seek psycho-behavioral treatment plans that include adjunctive therapy or alternatives to medication. Despite popularity, both “traditional” (cognitive behavioral therapy) and “new wave” (acceptance and mindfulness-based therapies) forms of alternative treatment have overall weak to moderate effect sizes for treating CP when compared to treatment as usual, passive controls, and/or educational support groups.

As a doctoral fellow in medicine specializing in pain treatment, I strongly believe that the development of innovative, safe, and effective means of treatment relies on our capacity to learn why patients diagnosed with CP can become addicted to opioids and investigate how we can nurture both the body and the brain in order to heal.

Pain is a multidimensional phenomenon, inseparable from our past and engrained within our inner and outer environment. It transforms our capacity to find meaning in life and changes the way we interact with ourselves and each other. Patients suffering from CP are constantly caught between the subjective and the objective meaning of their pain — imaging scans can sometimes show nothing and one-on-one interviews can sometimes reveal everything. However, as our technology evolves, the subjective feelings, thoughts, and beliefs of patients in pain are being revealed and acknowledged more than ever before.

Neuroimaging research suggests that the experience of pain emerges from an extensive network of brain regions comprising of sensory, emotional and cognitive aspects. As pain becomes chronic, there is a neurobiological shift within the brain from cognitive regions to more affective networks.

Yet the difficulty to know how opioids effect pain patients neurologically is simply due to the fact that nearly all neuroimaging studies of opioid analgesia have been performed in healthy volunteers, in whom the effects of opioids on acute painful stimuli are examined. The problem is that experimentally induced pain in a laboratory setting cannot realistically replicate the multidimensional distress experienced by patients with CP.

A big challenge within the field of pain research, pain management, and addiction is that there are very few neuroimaging studies which have been conducted on the long-term effects of opioids in patients with chronic nonmalignant pain.

In a study by Jarred Younger and colleagues, titled “Prescription opioid analgesics rapidly change the human brain,” individuals with chronic low back pain were administered daily doses of oral morphine for a total duration of one month and compared to those who used placebo. Compared to baseline scans, the researchers found significant volumetric differences in several regions of the brain, including the amygdala and anterior cingulate cortex between patients who were treated with morphine compared to those who received placebo. Surprisingly, the volumetric changes found in the morphine group persisted for months after cessation of opioids but no data regarding pain at that stage were reported.

Opioid transport across the blood brain barrier in the central nervous system is essential for establishing the euphoric effect one feels when taking opioids. In their article titled “GABAergic mechanisms of opiate reinforcement” Zheng-Xiong Xi and Elliot A. Stein explain how the reward system of the brain reacts systematically during opioid ingestion. Disinhibition of the GABAergic neurons located in the nucleus accumbens of the brain due to dopaminergic neurons originating from the ventral tegmental area increases activity in the ventral pallidum and in turn causes an increase of dopamine release. Over time, this dopaminergic release and reward effect may plateau or dwindle over time along with the analgesic effects depending on the rate and amount of opioid dosage. This can lead to opioid tolerance.

Opioid tolerance can occur in as little as two weeks while chronic administration of opioids can lead to a state of dependence. Due to the fact that opioids inhibit cell signals, cells will try to compensate by increasing their signaling capacity in order to return to normal functioning. Removing this inhibitory signal by taking away the opioids results in an overactivation of the affected cellular pathways which leads to a variety of symptoms driven by the somatomotor cortex and the autonomic nervous system.

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