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2015 Has Been a Good Year for Clinical Progress

Editor's Memo From December 2015

To read and listen to the mass media in 2015, one would think that pain management is interested only in the opioid and epidural injection controversies. But, it has been a good year for clinical progress. Although there were no headlines, this year has quietly seen some solid, scientific and clinical advances in pain management.

Therefore, my 2015 Science Breakthrough Award goes to the finding that circulating catecholamines—norepinephrine and metanephrine—control descending pain. Credit for this finding goes to the research team headed by Alexandre Parent, PhD, at the University of Sherbrooke, in Quebec, Canada.1

This finding has great practical significance. It tells us that we must not just treat ascending pain pathways with opioids and neuropathic agents; we also have to treat the descending pathway for optimal pain control. To do this, we must begin to administer adrenergic (eg, catecholaminergic) compounds in addition to our other treatments.

For example, catecholamine analogues such as dextroamphetamine and phentermine may now get strong consideration in chronic pain management. Therapeutic agents that have adrenergic or catecholaminergic activity, including some antidepressants, also need a renewed look. I’ve noticed that the opioid tapentadol (Nucynta), which has adrenergic activity, seems to be getting more popular. To those who champion natural approaches, please recall that the amino acids phenylalanine and tyrosine are the amino acid precursors of the catecholamines. Also, is anyone up for Starbucks?

In support of the excellent Canadian study, I have just reviewed an excellent prepublication study showing that catecholamine levels are reduced in women with reflex sympathetic dystrophy/complex regional pain syndrome.

Hopefully, commercial laboratories will soon take a page from these studies and begin providing serum catecholamine assays that have a normal range with both low and high levels. At this time, all the available commercial serum assays I’ve been able to identify have ranges from zero to some high level. To date, the only apparent reason serum catecholamine assays are performed is to determine if the serum level is above normal range to detect the possibility of pheochromocytoma. In chronic pain management, however, we need to know if there is a deficiency or low level, so we can justify the use of catecholaminergic drugs, which may carry a risk of abuse or toxicity.

Neuroinflammation and Centralized Pain

The other advance is the further identification, acceptance, and realization of centralized pain and neuroinflammation. This year has been the one in which this reality became known and accepted.2 Physiologically, centralized pain and neuroinflammation is caused by microglial cell activation. There are a number of basic science studies that implicate neuroinflammation as a major cause of persistent, chronic pain.

To help prove this point, I’ve embarked on a project to see if there is evidence of neuroinflammation in serum. I’ve found some serum markers of neuroinflammation and presented some early data in this regard.3 Two things are now clear to me. Neuroinflammation doesn’t respond well to the anti-inflammatory agents that effectively reduce inflammation in peripheral joints and muscles. Secondly, our opioids and neuropathic agents are pretty much symptomatic therapy and don’t get to the heart of the problem—which is neuroinflammation.

So important is neuroinflammation that one of our most capable and innovative pain practitioners in the United States, Gary Kaplan, DO, of McLean, Virginia, has started a research institute dedicated to finding treatments for neuroinflammation. Congratulations Gary and give us some answers forthrightly!!

In summary, this year has produced two real nuggets of knowledge that will help us improve pain care for our patients: catecholamine deficiencies and neuroinflammation. These two pathologic problems are far more important to future pain care than today’s controversies.

Last updated on: December 9, 2015
First published on: December 1, 2015
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PPM Editorial Board: Year in Pain Management 2015