Access to the PPM Journal and newsletters is FREE for clinicians.
10 Articles in Volume 17, Issue #4
Algopathy—Acknowledging the Pathological Process of Pain Chronification
Are Abuse-Deterrent Opioid Products A Double-Edged Sword?
CMS Tackles Opioid Prescribing
How do you handle end-of-life care in a patient who does not know they are dying?
Letters to the Editor: Functional Medicine, Naloxone, Hormone Testing, CRPS
Look at the Patient’s Life Story, Then Implement a Management Plan
Myofascial Pain: Overview of Treatment Options
Pain in Parkinson’s Disease: A Spotlight on Women
Patient in Pain? When to Refer for Physical Therapy
Somatic Symptom Disorder: DSM-5's Removal of Mind-Body Separation

Letters to the Editor: Functional Medicine, Naloxone, Hormone Testing, CRPS

May 2017

Functional Medicine

The case series using the functional medicine model was a very educational article.1 It would be useful to know about the cost and the possibility of insurance reimbursement for this pain management approach, so I might encourage my clients to consider this. I don’t expect that insurers in United States would cover tests or treatment provided by a functional medicine specialist. Also, how might I identify a naturopath who is well versed in these skills near my practice?

—Valerie M. Blais, BSN, LMT, CNT
Portland, Maine

Dear Valerie,

Actually, the current health care environment in the United States is uniquely situated to apply functional medicine into clinical practice. To my knowledge as a practicing physician, insurers reimburse many of the innovative functional tests typically requested. This is likely one of the contributing factors to the growing trend in referrals to functional medical specialists, more so in the US than in other parts of the world. However, according to the Institute for Functional Medicine, reimbursement by insurers is not typically granted for functional medicine testing at present, but this varies state by state and by specific insurer; patients should inquire about coverage prior to the doctor visit, and the physician may be able to assist in challenging the need for coverage.

There is a global movement toward systems biology as emerging data in genomics and metabolomics changes the one-size-fits-all medical model to a more predictive, personalized approach. Many centers, including the Cleveland Clinic, have recognized this paradigm shift and have incorporated the functional medicine model into their pain management programs.2

Training for naturopathic doctors (NDs) and medical doctors is available at the Institute for Functional Medicine in Washington, DC. Its website has a search tool to help you identify practitioners who have completed its courses. You can share this information with your patients.

Leigh Arseneau BSc, (hon.) ND

Practical Pain Management readers write in with their questions about hormone testing, functional medicine, CPRS.

Naloxone Risks?

It is my experience that there is an under-recognized risk of naloxone use in opioid-dependent patients, which was reinforced after I received 2 safety alerts—from Britain and Wales.3,4 How might I share this same warning with people in the US? I am concerned that many physicians do not address the chronic pain in patients who receive treatment in an acute setting for other medical crises. This means the pain condition is ignored, leading to extreme suffering and perhaps hastening a patient’s death, which I believe happened to my friend. I am aware of similar experiences, which have raised concerns about the legal and ethical issues surrounding withdrawal of essential pain relief without consent. In the case of my friend, her body will soon be autopsied—what might a pathologist look for to determine if pain was the cause of death?

—Richard Von Abendorff
London, United Kingdom

Dear Richard,

I’m delighted to hear that the England National Health Service has put out a safety alert to minimize the risk of distress and death from the inappropriate use of naloxone. As of now, I know of no such alerts in the United States, but I agree that it would be useful, and I am sorry to learn that your friend may have possibly lost her life to an inappropriate use of naloxone. I haven’t read any such reports in the United States, but I have received informal, unpublished reports.

First, the movement to give a naloxone kit to every pain patient is unwarranted. I have had health insurance companies urging me to prescribe a kit, which is quite expensive, for all my pain patients who have safely taken opioids for more than 20 years. One medical director of a prestigious health plan even went so far as to tell me that every patient who takes more than 100 mg of morphine equivalents a day will eventually overdose. Obviously, this medical director has never practiced pain medicine.

Your friend may be a victim of this ignorance. In my opinion, an opioid overdose worthy of naloxone has most of these physical findings:

  1. Miosis (pupil constricted under 3.0 mm (pinpoint) and non-reactive)
  2. Pulse rate 60 or under
  3. Blood pressure 90/50 mm Hg or less
  4. Respirations labored and under 10 a minute

Your friend may have arrived at a health care facility exhibiting symptoms of a disease or condition that was mistaken for an opioid overdose. The naloxone administration may have put her into a severe opioid withdrawal resulting in cardiac arrest. Unless all the physical signs noted above were present, she should not have been given naloxone—or she should have been given only a fraction (1/10 to 1/5) the usual dosage to assess if she may have overdosed.

Practical Pain Management has published articles about the cardiac hazard following a rapid withdrawal from opioids.5,6 During acute withdrawal, catecholamines rise rapidly in the serum, which can cause excess sympathetic activity. This spike in sympathetic activity constricts coronary blood vessels, which may produce an arrhythmia, infarction, or stroke. This is particularly true if the patient had underlying cardiovascular disease.

Do not look for answers from an autopsy, as it is unlikely for a patient who dies from cardiac arrhythmia to show any pathologic findings. If opioids are found in the blood, and absent any physical evidence for the death, the pathologist may declare an overdose.

Thank you for bringing this issue forward. 

—Forest Tennant, MD, DrPH

Hormone Testing

What type of doctor would you recommend I see for a hormone (metabolic) panel? I have already approached my primary care physician, my pain management doctor, my obstetrician/gynecologist, a dietician, a nutritionist, a psychologist, and a psychiatrist. They either told me that there is no need for such testing, or that my basic panel shows normal levels. However, I’ve been on opioid pain medication for 13 years, have had many steroid injections, and have taken oral steroids over the years.

Based on everything I have read about my symptoms, I am quite sure that my pain has affected my metabolism and disrupted my hormones, such as cortisol and adrenaline. No one will listen, but I am determined to find someone who will properly evaluate my hormone levels. Can you help?

—Bonnie Fricke
San Diego, California

Dear Bonnie,

Your inability to find health professionals who constructively respond to your request for hormone testing and treatment is a sad commentary, indeed. Put simply, chronic pain cannot be effectively managed by ignoring the profound, endocrine-related (hormonal) effects that are produced both by having chronic pain and from the effects of taking long-term, analgesic medications to control the pain. It seems you have found medical practitioners who believe they should only treat chronic pain with symptomatic drugs, or simplistic physical or psychological measures.

Some specific hormones control healing, suppress neuroinflammation, alter nerve conduction, and enhance receptor binding for analgesics used to control pain. For example, a chronic pain patient who is deficient in cortisol, pregnenolone, progesterone, estradiol, or testosterone may experience fatigue, insomnia, increased pain, and poor response to opioids and neuropathic agents (eg, gabapentin and duloxetine).

There are 2 types of hormone administration in pain management: replacement and therapeutic. With replacement, a hormone(s) that has been deemed deficient on serum testing is administered at a low dose for 3 to 5 days a week to restore hormones that have been depleted by the pain. Hormone replacement therapy is discontinued when the serum level returns to normal.  

Therapeutic hormone treatment, on the other hand, consists of temporary or intermittent hormone administration to suppress neuroinflammation, enhance pain control, and encourage permanent healing and pain reduction. Therapeutic hormones include oxytocin, human chorionic gonadotropin, and human growth hormone.

The basic hormone panel for pain management consists of 6 hormones: cortisol, dehydroepiandrosterone (DHEA), estradiol, pregnenolone, progesterone, and testosterone. This 6-panel profile is now available at all commercial laboratories and is performed from a single blood specimen drawn in the early morning. Receiving hormones both for replacement and therapeutically will usually reduce the need for opioids.

Keep searching for a medical practitioner who will work with you, even if you have to travel to find someone. A chronic pain patient who has been on pain medication for 13 years is simply risking too much from the effects that pain and drugs may have on the hormone system. Follow your instincts.

—Forest Tennant, MD, DrPH

Opioid Calculator

I reviewed your opioid calculator and found that the morphine milligram equivalents (MME) for buprenorphine were in line with other calculators. However, the notes listed below the calculator that indicate a much higher potency for buprenorphine confuse me. Specifically, note 6 states that 10 mcg with a Butrans patch equals 45 mg of morphine, which converts to 240 mcg/24 hours = 45 mg of morphine/24 hours.

While this seems to be a better approximation than the level given in the dose calculator, I do not know where this note is referenced. Would you explain the difference between the amounts indicated with the calculator and the note, and provide a reference for note 6?

—Joseph Walker III, MD
Farmington, Connecticut

Dear Dr. Walker,

Comparison of the mean serum levels (Cmax) of buprenorphine results in a conversion factor of 10 mcg/hour = 300 mcg/day when transitioning in either direction between transdermal (TD) buprenorphine and buccal buprenorphine. Using this conversion (and assuming the current morphine to TD buprenorphine equivalency programmed in the Practical Pain Management calculator), a morphine equivalent of ~40 mg/day would equal ~300 mcg/day (150 mcg every 12 hours) buccal buprenorphine when transitioning from a full-agonist opioid to buprenorphine. A morphine equivalent of ~45mg/day would equal ~300 mcg/day (150 mcg every 12 hours) buccal buprenorphine when transitioning from buccal buprenorphine to a full-agonist opioid. More detailed information is below.

Buprenorphine 10 mcg/hour patch results in a multiple-dose Cmax of 0.224 ng/mL, while single-dose 300 mcg buccal buprenorphine provides a Cmax of 0.47 ng/mL. Using these concentrations, 10 mcg/hour buprenorphine TD patch applied every 7 days chronically is equivalent to initial levels expected with ~143 mcg buccal buprenorphine dosed every 12 hours. Buprenorphine single-dose serum levels with the 10 mcg/hr patch achieved a Cmax of 0.191ng/mL, while the multiple-dose serum level achieved with 120 mcg buccal buprenorphine every 12 hours was 0.156 ng/mL. With these concentrations, ~147 mcg buccal buprenorphine dosed every 12 hours is equivalent to the initial serum levels expected from 10 mcg/hr buprenorphine TD patch every 7 days. The conclusion from studies attaining these serum levels indicated a linear increase in exposure and proportional Cmax increase as the dose increased.7,8

A recent study by Webster et al9 evaluated tolerability of switching patients on chronic full mu-opioid agonist therapy to buccal buprenorphine. While a 100:1 conversion ratio of morphine to buprenorphine was used to determine equivalency of dosing, the actual buprenorphine daily dose given was 50% of the morphine daily dose equivalent determined by the 100:1 conversion (ie, effective conversion was 200:1). The Webster study used a conversion factor of ~60 mg morphine/day equivalent to ~300 mcg buccal buprenorphine/day, or 150 mcg every 12 hours.9 This dosing paradigm resulted in no significant risk of opioid withdrawal or loss of pain control. One patient receiving buccal buprenorphine experienced a serious adverse event identified as chest pain and dyspnea, but no deaths occurred.9 This dosing schedule is more conservative than the dosing paradigm suggested by our established morphine/TD buprenorphine conversion and TD buprenorphine/buccal buprenorphine conversion proposed above.9

There is no difference in the dosing regardless of the calculation used—the calculator and calculations based on note 6 arrive at the same amounts. As for the reference for note 6, the recommendations and calculator are in line with the current package insert for Butrans;8 the specific conversion is 10 mcg/hour = 45 mg.

Jeffrey Fudin, RPh, PharmD

Joseph Gottwald, PharmD
Doctor of Medicine Candidate
Mayo Medical Schoo
Rochester, Minnesota


I was in a bad car accident 2 years ago, leaving me with chronic regional pain syndrome (CRPS), the loss of my job, and a dramatic change in my life. Following the accident, I went into menopause at the age of 38. Also, I have type 1 diabetes, which has been severely complicated by this awful pain disorder. I don’t live near any specialists to treat my condition, and my insurance is refusing coverage for pretty much everything. With all of this, I have had a difficult time caring for my 2 young boys.

In the past 2 years, all I have received is pain medication and a few nerve blocks. I just read an article on neurohormones,10 which I asked my doctor about months ago but got nowhere. I have spent thousands of dollars and countless hours seeking treatment for my CRPS. As a health care provider, I know enough to appreciate the potential pain relief of  hormone therapy. I also understand the benefits of getting off opioids because of their terrible side effects. Do you believe I would benefit from neurohormone therapy?

—Tisha Slater

Dear Tisha,

Your battle with CRPS is a tough one. Few physicians are familiar with this syndrome, and most pain specialists recommend a standard regimen of anti-seizure agents, antidepressants, and opioids to provide symptomatic relief. The new thrust is to treat CRPS with ketamine and/or neuromodulation by means of an implanted electrostimulator.

Your primary care provider can likely refer you to an interventional pain specialist who can give you a clinical trial with electrostimulation (ie, spinal cord stimulator) and help determine if your insurance will pay for it. Ketamine is now being offered as either an intravenous (IV) infusion, or by the oral, nasal, or sublingual routes. Physicians who perform ketamine infusions are scattered throughout the country, so you may have to travel to obtain this service. Since it is a costly procedure, you will want to work with your insurer to try to gain some reimbursement. Alternatively, oral ketamine is less potent than an IV infusion but far more affordable.

Although early in its conceptualization and formulation of treatment, some physicians and I are looking at RSD/CRPS not just as a defect in nerve conduction but also as a neuroinflammatory disease. Given this possibility, I now recommend that RSD/CRPS patients be evaluated and treated for neuroinflammation as an adjunct to the standard approach described above.

You are correct to be interested in the potential of neurohormones. This will be especially true if you fail to find much relief with electrostimulation, ketamine, and standard symptomatic pain relief. The use of neurohormones is complex and requires considerable testing and education, but a functional medicine specialist may help you recover and achieve some pain relief.

—Forest Tennant, MD, DrPH


I am a 60-year-old woman with arachnoiditis and a failed back surgery. I was diagnosed with scoliosis at age 14, which was treated with spinal fusion that helped until the rod broke at age 20, leading to a second spinal fusion.

When I turned 34 years old, I began having difficulty walking without pain. When I returned to the surgeon who assisted in my spinal fusion, he said I was healed. But after a year of chronic pain, I went to the Emory Spinal Clinic to have my x-rays reviewed. It seems I had no fusion from L5-S1 to L4-5, and the plate holding the pedicle screws in place had come out and was embedded in my abdominal aorta. A vascular surgeon removed the metal plate, then fused my spine from the front. A year later, I had a 15-hour surgery for spinal support from T10-L5-S1 with the hope of reducing my chronic pain.  

Recently, I started seeing a pain management physician who prescribed the pain infusion pump. Ten days later, I had extreme burning that ran down my right leg to my knee. Just a simple breeze caused extreme spasms that turned my right foot in, leaving me in dire pain.

My pain management specialist has been cutting back on my pain medications because of pressure from the recommendations on opioid prescribing issued by the Centers for Disease Control and Prevention (CDC),11 despite 20 years of necessary and responsible use. Members in my arachnoiditis support group have told me about your incredible pain management work. Can you offer guidance on how I can better control my pain?

—Denee Hand
Atlanta, GA

Dear Denee,

I’m sorry to hear of your suffering. It appears that your condition is one in which the CDC guidelines allow for an exemption to take opioids above 90 mg morphine equivalents a day.11

In addition, the term arachnoiditis means “inflammation of the spinal canal covering or lining.” Adhesive arachnoiditis (AA) means you have adhesions attaching your arachnoid lining to some of your nerve roots in the lumbar spine (cauda equina). The basic cause of pain is usually neuroinflammation around the nerve roots of the central nervous system (CNS). The missing link in treating arachnoiditis, and likely other painful CNS inflammatory conditions (eg, chronic regional pain syndrome), is a failure to treat the neuroinflammation.

Opioids and most other drugs used in pain management address pain symptoms but do little to suppress neuroinflammation, which is now known to occur when microglial cells are activated, which occurs in AA.

A medical regimen for relief and recovery must be simultaneously administered to control both neuroinflammation and severe pain. Once the neuroinflammation and pain are brought under control, a program of specific nutrition, spinal cord exercises, and hormone administration may provide some neurogenic nerve regrowth and adhesion resolution that may offer some permanent pain relief and foster recovery.

Currently, there’s no standard regimen for treating AA. The approach I recommend is a work in progress, but it seems to provide some good relief and recovery for many of my patients. My first step is to request a blood test for the inflammatory markers (C-reactive protein and erythrocyte sedimentation rate) and the cytokines (interleukin and tumor necrosis factor).

In my approach, there are 3 components to the starting regimen, in which I prescribe the following:

  • Low, afternoon dose of dexamethasone or methylprednisolone
  • Indomethacin with meals
  • A glial cell modulator at bedtime (eg, metformin, acetazolamide, pentoxifylline)

If some serum inflammatory markers are elevated, I might consider adding a ketorolac injection or spray once or twice weekly as a supplementary anti-inflammatory measure. The agents I use are initially given only 3 to 5 days a week to prevent complications and provide room for dosage and frequency escalation.

Patients usually achieve pain relief when they follow this 3- or 4-step process. Since neurogenic measures for AA are complex (they require more instruction than I can provide in this brief response); hopefully, you can find a physician who can guide you in the emerging medical protocols to treat neuroinflammatory pain diseases.

—Forest Tennant, MD, DrPH

Last updated on: September 27, 2017
Continue Reading:
Myofascial Pain: Overview of Treatment Options

Join The Conversation

Register or Log-in to Join the Conversation
close X