Opioid Antagonists in Chronic Pain Management

A Fresh Look at Opioid Antagonists in Chronic Pain Management – October 16, 2017 – By Dmitry M. Arbuck, MD

The article explains how these drugs are *not* effective for the pain from physical damage but are able to reduce the pain from neurological “central pain sensitization”.

As clinicians reduce their reliance on opioids for the treatment of pain, they are turning to a wider array of pharmacological tools and approaches to help overcome deficiencies of opioids, such as treatment-limiting side effects, and as aids in relieving difficult-to-treat pain conditions.

One such approach is the use of opioid antagonists. The use of opioid antagonists—in particular, naltrexone and naloxone—in chronic pain management is not new, but it deserves more recognition and acceptance than it enjoys presently.  

Reward Processing by the Opioid System in the Brain

Reward Processing by the Opioid System in the Brain – free full-text PMC article – Physiol Rev. 2009 Oct;

The opioid system consists of three receptors, mu, delta, and kappa, which are activated by endogenous opioid peptides processed from three protein precursors, proopiomelanocortin, proenkephalin, and prodynorphin.

Opioid receptors are recruited in response to natural rewarding stimuli and drugs of abuse, and both endogenous opioids and their receptors are modified as addiction develops.

Mechanisms whereby aberrant activation and modifications of the opioid system contribute to drug craving and relapse remain to be clarified. 

Beta-endorphin and endogenous opioid function

What do plasma beta-endorphin levels reveal about endogenous opioid analgesic function? – Sept 2003 – free full-text PMC article

Plasma levels of beta-endorphin (BE), an endogenous opioid analgesic, are often reported as they relate to acute and chronic pain outcomes.

However, little is known about what resting plasma BE levels might reveal about functioning of the endogenous opioid antinociceptive system.

This study directly examined associations between resting plasma BE and subsequent endogenous opioid analgesic responses to acute pain in 39 healthy controls and 37 individuals with chronic low back pain (LBP).

Endorphins: Our Own ‘Natural Opioids’

The reason opioid medications work so well is that they mimic the structure and function of the opioids naturally produced by our own bodies.

This is also why I’m more comfortable with these medications than many of the other strange molecules designed to ease pain, like antiepileptics and antidepressants.

First, some basic definitions from Wikipedia:

Endorphins – Wikipedia

Endorphins (contracted from “endogenous morphine”[note 1]) are endogenous  opioid neuropeptides in humans and other animals. 

Borderline Personality Disorder: Shortage of Endogenous Opioids?

Borderline Personality Disorder: A Dysregulation of the Endogenous Opioid System? – Psychological Review – ResearchGate – April 2010 – free PDF Download Available

The neurobiology of borderline personality disorder (BPD) remains unclear. Dysfunctions of several neurobiological systems, including serotoninergic, dopaminergic, and other neurotransmitter systems, have been discussed.

Here we present a theory that alterations in the sensitivity of opioid receptors or the availability of endogenous opioids constitute part of the underlying pathophysiology of BPD.

This is a radical idea, but I’ve read it before: certain psychological states in certain people can be relieved by opioids. However, even if this proves to be true, we certainly won’t be prescribed this particular drug, no matter how effective it is at easing mental disorders since it’s not even being used for physical pain anymore. 

Neurohormones in Pain and Headache Mgmt

Neurohormones in Pain and Headache Management: New and Emerging Concepts – practicalpainmanagement.com – Feb 2017

The recent discovery and awareness that the central nervous system (CNS) makes specific hormones for intrinsic use in addition to those for peripheral use is a profound finding that is critical to clinical pain and headache management.

Some neurohormones provide the physiologic effects of neuroprotection and neurogenesis that are essential for pain reduction, prevention, and treatment.

Following is an attempt to provide an early status report on what we do (and don’t) know about the function of neurohormones relative to pain management.  

Opioids and the Treatment of Chronic Pain

Opioids and the Treatment of Chronic Pain: Controversies, Current Status, and Future Directions –  free full-text PMC article – Jul 2009

In most individuals, when opioids are taken to treat pain, there appears to be no overt effect from change in these systems. In some cases, however, powerful reinforcement occurs…

Opioids play a unique role in society. They are widely feared compounds, which are associated with abuse, addiction and the dire consequences of diversion; they are also essential medications, the most effective drugs for the relief of pain and suffering

This is a long post because the article contained so many gems of information (with references!).  

Opioids + Pain != Euphoria

Psychoactive Properties of Opioids and the Experience of Pain –  Journal of Pain and Symptom Management – February 2016

Here is a letter to the editor of a pain journal from Stephen R. Connor, PhD of the Worldwide Hospice Palliative Care Alliance.  

He points out what so many of us have noticed: if you take opioids when you’re in pain, you do not get “high” (see also Opioids, Endorphins, and Euphoria)

A frequently held view in palliative care is that when patients in pain use opioids, they do not experience the psychoactive or euphoric effects of opioids.

Furthermore, that those not in pain who use opioids do experience these euphoric effects that may lead to opioid-use disorder.  

Problems with Pain Processing in Fibromyalgia

Fibromyalgia and the Brain: New Clues Reveal How Pain and Therapies are Processed – 7-Nov-2012

Though this study is 5 years old, there hasn’t been much follow-up on what was discovered: “Some individuals with fibromyalgia may have a down-regulation or decrease in opioid receptor activity that may exaggerate pain sensitivity”

Previous studies indicate that fibromyalgia patients have increased sensitivity to temperature, touch, and pressure.

Moreover, some of Dr. Harris’s previous work demonstrated that people with fibromyalgia produce an increased amount of endogenous opioid peptides (also known as endorphins that naturally relieve pain) that act on the brain’s μ-opioid receptors to “naturally” reduce pain.  

Understanding Electromagnetic Treatments – latest version

Understanding Electromagnetic Treatments – Practical Pain Management | November 30, 2011

With so much emphasis on using alternative medicine instead of opioids, this is a treatment without chemical side effects that holds some promise, at least for the few who

1. have the kind of pain these treatments can relieve.
2. have insurance that covers a sufficient number of treatments and who

Below is a thorough article by Dr. Forest Tennant, explaining how electricity flows through our bodies and how electromagnetic treatments affect it.

His theory is that pain causes electricity to pool instead of flowing freely, thus initiating a cycle of increasing tissue damage, pain, and impairment. This is a long and detailed explanation of electromagnetic forces and how they relate to pain from damaged nerves:

“A fundamental to understanding electromagnetic measures is the pooling of electric charges around damaged nerves.”