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10 Articles in Volume 16, Issue #4
Achilles Tendon Injuries
Brain Trauma in Sports
Genetic Testing: Adjunct in the Medical Management of Chronic Pain
Letters to the Editor: Sleep Apnea, SPG Blocks for Migraines, Pancreatic Pain, CDC Guidelines
Pain and Weather—A Cloudy Issue
Phulchand Prithvi Raj, MD, Pioneer in Pain Management, Dies at 84
Physical Medicine & Rehabilitation
Preventing Chronic Overuse Sports Injuries
Sports-Related Pain: Topical Treatments
The “Missing Link” in the Physiology of Pain: Glial Cells

Letters to the Editor: Sleep Apnea, SPG Blocks for Migraines, Pancreatic Pain, CDC Guidelines

May 2016

Sleep Apnea and Testosterone

A recent Letter to the Editor reminded me of my appreciation for Dr. Tennant’s work to make neurohormonal supplementation or replacement credible, as well as putting it in perspective as a component of the pain practice.

For over 3 decades, I have worked to assemble treatment teams for chronic pain or dysfunction. During this period, I have included testosterone and human chorionic gonadotropin (hCG) in my protocols, and routinely include testosterone in prolotherapy blends. I am writing, though, to suggest that sleep disordered breathing (SDB or sleep apnea) should also be considered as a contraindication to testosterone replacement therapy (TRT).

I believe that research will find that chronic TRT worsens SDB and may be a significant factor in the relationship between TRT and heart disease or stroke. I feel that periods of TRT or hCG can be helpful in combination with other therapies and life-style changes. I am hoping that research confirming the benefits and outlining the risks (and modifiers) for TRT can be forthcoming before its availability is curtailed.

Sincerely,

Darick Nordstrom, DDS

 

Dear Dr. Nordstrom,

Your experience with TRT is well received. Now that you mention it, I think I’ve made the same observations without connecting the dots.

The co-occurrence of sleep disorders and pain is well known. According to the literature, sleep and fatigue symptoms have surpassed pain as the most prominent complaints in fibromyalgia patients, for example.1 It is also now recognized that sleep and pain are bidirectional, meaning poor sleep can predict chronic pain, and poor pain management contributes to sleep problems.2-4 Conversely, good sleep appears to improve the long-term prognosis of individuals with chronic pain conditions.

Therefore, it is not uncommon to conduct a sleep history when taking a medical history of a patient with pain. If sleep apnea is suspected, then early diagnosis and management are key to improved pain and sleep. Also known, but maybe not as recognized, is the role medications play in disrupting sleep. A growing body of research has repeatedly demonstrated that opioids disrupt sleep architecture and inhibit REM sleep.5,6

Beyond its role in sexual performance, testosterone plays a much wider and more critical role in pain management. Testosterone enhances analgesia, healing, and the immune response. It also is critical for prevention of osteoporosis, depression, and immobility. Without adequate serum testosterone levels, pain patients may complain not only of weakness, fatigue, depression, and loss of libido, but also poor pain control and hyperalgesia.

Thanks for sharing as your tip may be lifesaving to someone with SDB.

Forest Tennant, MD, DrPH

Dr. Nordstrom.

Exploration of hormone replacement therapy for patients experiencing chronic pain has been increasing in popularity over the last few years. It is well established that long-term opioid therapy can influence androgen deficiency. Endogenous testosterone rises and falls in a circadian fashion and varying levels are affected by the onset of rapid eye movement (REM) sleep.7 Once peak level is reached, it is sustained until morning and then decreases during the day.

Diminished REM sleep is found to correlate with decreased testosterone levels.7 And, a previous theory hypothesized that low testosterone levels may correlate with obstructive sleep apnea (OSA) due to decreased time spent in REM sleep.  Correcting OSA with continuous positive airway pressure (CPAP) could at least theoretically increase testosterone levels; however, a meta-analysis performed by Zhang et al found no change in serum testosterone following CPAP intervention.7,8

Historically, OSA has been considered a contraindication to initiating testosterone replacement therapy (TRT), and in fact, the 2010 Endocrinology guidelines recommend against use in patients with OSA.9 The guidelines, however, admit this to be a recommendation with little supporting evidence and in fact recent research has given reason to re-examine.9-12

In 2003, Liu et al found short term TRT (3 weeks) to reduce sleep and worsen breathing; however, no anatomical changes were seen in this short duration.10 More recently, a randomized control trial performed by Hoyos et al examined the effects of long-term testosterone replacement therapy on OSA in 67 obese men.11 They found at 7 weeks of therapy a mild worsening of oxygen desaturation index and nocturnal hypoxemia compared to placebo; however, at 18 weeks of therapy this resolved.11 A subset of this study examined 21 men in an attempt to determine a mechanism for this change.12 The study hypothesized that the temporary effects might have been due to changes in chemoreflexes; however, the group instead found a correlation with hyperoxic ventilatory recruitment threshold and both serum testosterone and oxygen saturations.12 Certainly this evidence does not represent a green light for initiation of TRT in individuals with OSA but rather highlights the need for additional trials examining long-term therapy with an update to the current guidelines.

Erica Wegrzyn, BA, BS, PharmD
PGY1, Pharmacy Resident
MaineGeneral Medical Center
Augusta ME

Jeffrey Fudin, BS, PharmD, FCCP, FASHP
CEO, Remitigate LLC
Director, Pain and Palliative Care Residency at Stratton VA Medical Center in Albany NY
Adjunct Associate Professor, Western New England University College of Pharmacy in Springfield MA

 

SPG Blocks for Migraines

In the recent article on sphenopalatine ganglion (SPG) blocks for migraines, there was an error in the parasympathetic pathways (Figure 1).13 It is the lacrimal nucleus that sends fibers through this ganglion. The superior salivatory nucleus sends its fibers through the submandibular (submaxillary) ganglion.

Could this block have any benefit in treating spinal headaches, as sometimes the triptans do?

G. Chudolij, MD

Dear Dr. Chudolij,
It is indeed correct that it is the lacrimal nucleus that sends fibers through the SPG. Most resources don’t differentiate the lacrimal nucleus from the salutatory nucleus, but if you look further, it is specifically the lacrimal nucleus that sends parasympathetics that end in the sphenopalatine ganglion. This is a relatively new technique being used in clinical practice, and as far as we know there is no literature indicating its use or effectiveness in spinal headaches, and we have not tried SPG blocks for spinal headaches. For refractory spinal headaches that don’t respond to usual treatment of hydration, caffeine, and blood patches, it is definitely worth trying the SPG block, which is a safe and simple procedure.

[Editor’s Note: In the April issue of Practical Pain Management, Patel et al reported on the use of SPG to stop post-dural puncture headaches in women after delivery.14]

Soma Sahai-Srivastava, MD and Kellie Spector, BS

Headache & Neuralgia Center

Keck School of Medicine

University of Southern California,

Los Angeles, CA

Pancreatic Pain

Dear Dr. Tennant,

I had a total pancreatectomy with subsequent lower left quadrant pain since 2005. A new physician who I am seeing is tapering my dose of pain medication by 5 mg every 2 weeks—my starting dose was 130 mg per day [type of opioid not given].

My question is how do I know if the dendrites are permanently retracted into the neuron? Will I be completely (or just for a long time) unable to produce endogenous endorphins on my own?

Charlie Solender, RN

Dear Charlie,

Your tapering schedule looks quite appropriate to me. While everyone wants to “taper” or “get off” opioids, I find the frenzy to do this is too often misplaced.

First, I find that too many patients and physicians want to taper patients when they still have severe, disabling pain. Tapering should only be attempted when pain has been greatly diminished or resolved, and it is clear that a lower dose of another opioid or a zero dose will do.

Second, no tapering should be done unless the physician and patient have a preset goal and plan. For example, what is the plan if the taper is halfway completed, but pain returns? When, and will, another opioid (eg, short-acting or long-acting) be substituted when the taper is half done, totally done, etc?

Little is known about neuroregeneration or endogenous endorphin levels following opioid withdrawal. I have observed one thing that I recommend be kept in mind. If a taper is done too quickly without a goal or plan, patients may end up with worse pain and disability.

In summary, taper slowly with a goal and plan to avoid recurrence of pain.

Forest Tennant, MD, DrPH

Post-Op Guidelines

I have to protest a statement in the article “New guidelines for postoperative pain management.”15 The statement: “When treating opioid-naïve adults, clinicians should avoid routine basal infusion of opioids with IV PCA [patient-controlled analgesia], given that there are not known improvements to analgesia with this technique...” There is no study footnoted in this paragraph that gives evidence to this statement.

I can think of 5 randomized controlled trials that prove that patients used opioids less frequently and in smaller doses when allowed a PCA with basal rates.16-20 As a nurse practitioner who has been practicing nursing and medicine for 30+ years, I have seen the pain management issue come around full-circle. First in the 1980s and 1990s, nurses ran around with orders for meperidine [Demerol] injections every 4 hours, as needed (q4h prn). This prescription did not relieve patients’ pain. Some patient’s only got 2 or 3 hours of relief, and nurses had to hold their hand for the last hour when they had no relief. Making matters worse, it was difficult to get a physician, especially surgeons, to return our calls.

Then the Joint Commission on Accreditation of Healthcare Organizations (JCAHO) noted that 75% of all hospital patients had under- treatment of pain—making it the “5th vital sign.” Now, we are told, do less, no basal, and let them tough it out. That, at least, is what the new guidelines seem to imply. How do we find a legal and safe profile balance for perioperative patients?

Rebecca Cailor, RN

Dear Rebecca,

Welcome to the new world of “guideline of the month.” We went back to the PDF of the guidelines and found 2 references in support of their statement: Rodgers A, Walker N, Schug S, et al. Reduction of postoperative mortality and morbidity with epidural or spinal anaesthesia: results from overview of randomised trials. BMJ. 2000;321:1-11, and Snell P, Hicks C. An exploratory study in the UK of the effectiveness of three different pain management regimens for post-caesarean section women. Midwifery. 2006;22:249-261. In the section on systemic pharmacological therapies, there are 9 individual recommendations, which we encourage you to read in full.

The guidelines go into more details about IV PCA as reprinted here: “In patients who receive IV PCA, the panel does not recommend the routine use of basal infusion of opioids in opioid-naïve patients, because most evidence shows no improved analgesia compared with PCA without a basal infusion (reference numbers from the original report: 115,219,220,248). In addition, basal infusion of opioids is associated with an increased risk of nausea and vomiting, and in some studies with increased risk of respiratory depression in adults (ref. 99).” For opioid-tolerant patients, noted the panel, “there might be a stronger rationale for its use because of the potential for under dosing and uncontrolled pain, as well as opioid withdrawal, particularly in patients who received long-term opioid therapy before surgery. As for children, “There is insufficient evidence to guide recommendations on use of basal infusion of opioids in children, although some evidence suggests that a low basal rate can be used safely (ref. 317).”

When attempting to interpret guidelines and decide whether to follow them, take a hard look at the panel members who wrote them. Who do they represent? These days it’s mostly the “bigs—big pharma, hospitals, insurance companies, universities, drugstore chains, or government entities. Besides a financial motivation, beware of the clichés being used by the guideline committees. The most common excuse today is: “There is no evidence” to support xyz. Forget the fact that the drug or procedure may have been around for dozens of years and successfully used by millions of patients. Everyone publishes “evidence-based” guidelines. It just so happens that they select and choose their evidence!

Remember, guidelines are not requirements. Stay with what you know works. There’s an old adage in medicine “Do what you know works, and keep doing it.” Your comment that “do less and let them tough it out” does seem to be what some parties want. Our job hasn’t changed—prevent suffering.

Forest Tennant, MD, DrPH
 

CDC Guidelines

I read the opinions of the Practical Pain Management’s Editorial Board Panel regarding the CDC guidelines.21 I am an anesthesiologist who is fellowship trained and board certified in pain management. I began my career with no particular bias for or against opioids. I quickly noticed, however, that none of the patients who came to me on high-dose, or for that matter low-dose, opioids seemed to be doing very well.

I began to move away from the use of opioids, instituting drug holidays instead of increasing the dosage of medications. When faced with an opioid holiday, about 15% of patients went somewhere else for care, but the remaining 85% of patients who were weaned off opioids did not want to restart them.

I have had patients tell me they can’t believe how much better they feel without the opioids, how much clearer they are thinking, and how they have improved energy and function. I had a patient who had been on about 120 morphine milligram equivalents per day for over 4 years tell me: “I can’t believe I gave up 4 years of my life and the conscious time with my family for those drugs.”

What bothers me is that the alternatives to opioids mentioned in the guidelines do not have good evidence of effectiveness (eg, acupuncture, transcranial electrical stimulation, progressive relaxation, yoga). All of these approaches have value as ancillary approaches, but most of my patients have tried some variation of these, plus physical therapy, before they ever see me.

As interventionalists, we have a number of treatment options (eg, epidural steroid injections, cryoablation, pulsed radio frequency ablation, spinal cord stimulation, etc), but these are not mentioned. I know there is a mixed bag of research on some of these techniques. But in my experience using fluoroscopic guidance and careful placement of the needles, 80% of my patients are improved over baseline at their 4-month follow-up. Of these, a substantial number have decreased or eliminated their pain medicines, and about a quarter are “cured.”

I know there are many people performing these procedures in a sloppy manner, but when done carefully, they are a very powerful addition to the treatment of acute and chronic pain.

Victor M. Taylor, MD, DABA

Last updated on: May 17, 2016
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Brain Trauma in Sports

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