Pain, Survival, Opioids and Addiction: Activation of Opioidergic and Dopaminergic Circuitry in the Mid-Brain

Opioids and Addiction

At present, opioids are the most widely used and effective medications for the treatment of moderate-to-severe pain. The recent opioid crisis has caused many to reevaluate this practice. Yet the mechanisms of acute versus chronic pain, and how pain relief may involve activation of opioidergic and dopaminergic circuitry in the cortico-limbic regions has resulted in renewed interest and investigation regarding what pain is and is not. At the most primitive level, pain, like hunger, thirst, desire for sex and need to sleep, is inexorably connected to our innate survival system. This system’s primary function is survival.

Our most primitive emotional responses, including pain, are characterized by specific somatic and emotional sensations that compel action when deviation from homeostasis is detected. The reward hypothesis of addiction we posited and tested nearly 40 years ago demonstrated that after detoxification and months of confinement in a safe and secure clinical setting, most heroin/opioid addicts quickly returned to drug use. This was not because they were experiencing the pangs of withdrawal but because their brains had undergone neuroadaptation and sought pleasure even when harmful and life-threatening consequences were known, predictable and often imminent. What we learned was that opioids, alcohol and most drugs of abuse change our basic survival system. Yet for persons with chronic intractable pain, physical dependence on opioids is a certainty. When managed by doctors trained in pain management, psychiatry or anesthesia who are also credentialed in addiction medicine, abuse or addiction to opioids is not the norm or expected outcome.

Why Does This Matter?

  1.  Pain medications may be overly rewarding, but so is almost anything that produces a relief of ongoing pain. In fact, imaging studies has demonstrated that relief of acute pain produced a strong neuronal signal in the Nucleus Accumbens (NAc), an area in the primitive mid-brain associated with reward-aversion processing in humans.
  2. Multiple studies have demonstrated that opioid drugs have a specific effect on the quality and perception of pain.
  3. Pain can produce a reward deficiency syndrome, as does chronic opioid self-administration.

The role of endogenous opioid activity in pain relief and addictive disease has been demonstrated by imaging studies in healthy volunteers. Learning how to increase endogenous rewarding mechanisms is an important research and clinical question.

For now, the good news is that Mindfulness Meditation has been shown to decrease dependence on illicit opioids, most likely through activation of innate reward mechanisms.