The Bench Delivers and It Matters
Bench to bedside. It’s an old adage that has long characterized a system that produces the best medical care. At Practical Pain Management we tend to focus on the “bedside” part of the equation—the practical treatments that grow out of bench research. This month, I’m going to change this focus, and take a moment to highlight the vital role that the bench plays, and also to raise some concerns about the future of bench research.
This editorial was motivated by a paper in a recent edition of the Journal of Pain.1 While leafing through the journal I came across a study titled “Conditioned Place Preference Reveals Tonic Pain in an Animal Model of Central Pain.” Although hardly a title to tickle the fancy of a practicing physician, I began to read and my mind was soon fully engaged. In this fine study, scientists Davoody et al describe the first live animal model that can be used to evaluate central pain agents.1
Their report succinctly summarizes some of the many excellent studies that have documented that a peripheral nerve injury, if not rapidly cured, may transform into central pain via microglial cell activation, uncontrolled neuroinflammation, and abnormal central nervous system (CNS) cell reformation. These researchers were able to determine that their spine-injured rats developed chronic central pain (called spontaneous or tonic by these researchers) and that their rats responded to clonidine or motor cortex stimulation by electric current. It is excellent and promising research and tells us that a much closer look is needed at clonidine and electrical stimulation of the CNS. I wonder what treatments to help our patients may be borne from this research?
I could of course list numerous examples of fine bench research, the results of which help to shape our clinical treatments. That is beyond the scope of this editorial so I will simply “doff my hat” to the bench researchers in great appreciation of the vital and high-quality work they do.
Although it is right to celebrate bench research, the topic also raises concerns for me regarding the communication between researchers and clinicians. It is my observation that there is an increasingly gross communication gap between our excellent cadre of basic science pain researchers and those of us who treat patients. A generation ago, universities and hospitals fostered this communication, but today this channel of communication seems diminished. Is it due to patient overload and financial pressures making it harder for the clinician to step back and review new and emerging research? I’m not sure, but a gap is emerging. Look at the participants at PainWeek and those at the American Pain Society’s (APS) annual meeting and there is only modest cross-over. Clinicians primarily go to one program, scientists the other.
And this breakdown in communication does matter. For example, elsewhere in this issue I describe the rather good results of topical opioids in patients with central pain. Frequently I am asked, “Why topical opioids?” Incredibly, the bench discovered opioid receptors in peripheral tissue more than 20 years ago, but from the questions I receive it seems that many clinicians don’t yet know this.2-4
How about this question: “Do you use stimulants with pain patients?” Basic science long ago showed that stimulants should be part and parcel of opioid treatment.5-9 Are you aware that the “bench” has published animal studies showing that minocycline, acetazolamide, pentoxifylline, human chorionic gonadotropin, pregnenolone, and progesterone, may either inhibit neuroinflammation and or regenerate CNS tissue?10-16 Do you use an electromagnetic device in your practice? There’s plenty of basic science showing that these new devices have considerable regenerative powers, with pain relief a result.17,18 Yes, the communication gap matters.
The Davoody article also points out the breakdown of communication between our “bench” and our “bedside” in the vocabulary that is used. The researchers refer to spontaneous or tonic pain, terms that I have never heard at a clinical pain meeting, nor read in a clinical journal. Has any clinician ever used the term spontaneous pain before? The researchers explain their newly created term to be “persisting pain in the absence of an insult.” At the “bedside” I simply ask the patient if his or her pain is constant—“24/7”—or intermittent. The big problem here is that basic science researchers are establishing a vocabulary in the literature that neither the practitioner nor clinical researchers can use. Greater communication between both sides on these topics would serve patients well.
I conclude with an exhortation to our readers. Try to take a little extra time to keep up with the basic science research. Although much of it will not impact how you treat your patients today, some of it will. And even if the research is not relevant immediately, the papers will stir your creative juices and strengthen your knowledge of this complex field. As a resource, I recommend to you the APS’ Journal of Pain, which is chock full of basic science studies. And Practical Pain Management will also strive to occasionally update you on research that we believe to be of particular importance. So, please take some time to dive into the research because greater awareness of the bench will help us all at the bedside.