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Pain

Lidocaine is an effective local anesthetic that is injected for dental procedures, minor surgeries, as well as nerve blocks, including nerve blocks for migraines, cluster, and other types of headaches. Since it is a numbing medicine, lidocaine has been also given intravenously in the hope of relieving widespread pain or pain that does not respond to local injections. Unfortunately, it is not as effective intravenously as it is for local injections and nerve blocks for either headaches or other pain conditions.

A controlled study of intravenous lidocaine for pain was just published by Korean researchers in the Regional Anesthesia and Pain Medicine“Efficacy and Safety of Lidocaine Infusion Treatment for Neuropathic Pain: A Randomized, Double-Blind, and Placebo-Controlled Study“.

The researchers decided to examine whether pain relief from intravenous lidocaine can be sustained through repeated lidocaine infusions. This was a randomized, double-blind, placebo-controlled study of infusions of lidocaine (3 mg/kg of lidocaine administered over 1 hour) vs infusions of normal saline, given once a week for 4 consecutive weeks in patients with postherpetic neuralgia or complex regional pain syndrome (formerly called RSD, or reflex sympathetic dystrophy). The results were assessed by the change in pain score from baseline to after the fourth infusion and then again, 4 weeks later.

Forty-two patients completed this study and the percentage reduction in pain scores after the final infusion was significantly greater in the lidocaine group compared with the saline group. However, this pain reduction was not detectable at the 4-week follow-up. None of the study participants experienced serious complications from the treatment.

So, while repeated lidocaine infusions did provide effective short-term pain relief, the effect did not persist.

I have had several of my patients with severe chronic migraines respond to intravenous lidocaine, but their experience was similar – they had to get weekly infusions to maintain good relief. Because intravenous lidocaine can cause irregular heart beat (arrhythmia), cardiac monitoring is required. This makes weekly intravenous lidocaine infusions even more expensive and impractical for most pain and headache sufferers.

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Psychological factors play a major role in migraines. This is not to say that migraine is a psychological disorder – we have good genetic and brain imaging studies confirming its strong biological underpinnings. The divide between biological and psychological is very artificial since we know that physical illness leads to psychological problems and the other way around. Stress is obviously one of the major triggers of migraines and we know that people with migraines are at least twice as likely to develop anxiety, depression, and other mental disorders. These are not cause-and-effect relationships because anxiety and depression can precede the onset of migraines. The connection is probably due to shared underlying problems with serotonin, dopamine, and other neurotransmitters.

We have strong evidence that addressing psychological factors involved in migraines through biofeedback, meditation, and cognitive therapy can lead to the reduction of migraine frequency, severity, and disability. Studies in chronic pain patients have shown that people with external locus of control (thinking that uncontrollable outside chance events are major contributors to pain) have more disability than people with internal locus of control (those who feel that their actions are contributing to pain and that active involvement in treatment can relieve pain).

Chronic migraine sufferers (defined as those with 15 or more headache days each month) are known to have greater disability than those with episodic migraines. In a recent study by researchers at the Yeshiva University and Albert Einstein College of Medicine, 90 chronic migraine patients were evaluated for psychological symptoms. Of these 90 patients, 85% were women, their mean age was 45, and half reported severe migraine-related disability. They were twice as likely to be depressed and to have external locus of control. The half with severe migraine-related disability were 3.5 times more likely to have anxiety and depression and were twice as likely to have a symptom described as catastrophizing. Catastrophizing is defined as having irrational thoughts about pain being uncontrollable, leading to disability, loss of a job, partner, ruined life, etc.

The good news is that many studies show that with cognitive therapy locus of control can be shifted from external to internal, catastrophizing can be reduced or eliminated, and disability diminished. This may not eliminate migraines or chronic pain, but can make you less anxious and depressed, and much more functional. Cost and access to therapy can be a problem, but studies suggest that even online therapy can be very effective.

Besides psychological approaches, regular aerobic exercise (stationary bike is easiest for migraine sufferers), certain supplements and prescription drugs can also help. Supplements that can relieve anxiety and depression include SAMe, omega-3 fatty acids (fish oil), methylfolate, and other. Some antidepressant medications relieve not only anxiety and depression, but also provide relief of migraines even when psychological factors are absent. These include so called SNRIs (duloxetine or Cymbalta, venlafaxin, or Effexor, and other) and tricyclics (amitriptyline, or Elavil, protriptyline, or Vivactil, and other). The most popular group of antidepressants, the SSRIs (fluoxetine, or Prozac, escitalopram, or Lexapro, and other) do help anxiety and depression, but have no pain or headache-relieving properties. Obviously, all drugs have potential side effects and for most patients it makes sense to try non-drug treatments first.

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The field of marijuana research is starting to take off due to the wider acceptance of medicinal marijuana. The other night I attended a lecture in NYC by the “father of cannabis”, Raphael Mechoulam.

According to Wikipedia, “Dr. Mechoulam is an Israeli organic chemist and professor of Medicinal Chemistry at the Hebrew University of Jerusalem in Israel. Mechoulam is best known for his work (together with Y. Gaoni) in the isolation, structure elucidation and total synthesis of THC (?9-tetrahydrocannabinol), the main active ingredient of cannabis and for the isolation and the identification of the endogenous cannabinoids anandamide from the brain and 2-arachidonoyl glycerol (2-AG) from peripheral organs together with his students, postdocs and collaborators.”

Dr. Mechoulam identified THC in 1964 and in his lecture he lamented the paucity of research into the many potential healing properties of cannabis in the past 50 years. He strongly feels that the two main active ingredients in marijuana, THC and CBD should be tested rigorously in large double-blind studies just like any other prescription drug. This will allow doctors to prescribe a proven medicine, rather than rely on anecdotal reports and go through trial and error, as we are doing now. His research suggests that cannabis ingredients could possibly help a wide variety of conditions, from diabetes and cancer to pain and nausea.

Prescribing medical marijuana is at least possible in New York and 20 other states, so that we do not have to wait, possibly up to 10 years, for a cannabis-based drug to be approved by the FDA (one CBD-containing drug might be approved soon for a rare form of epilepsy).

At this time we have to go through trials of various ratios of THC and CBD and various modes of delivery (inhaled, sublingual or oral) to determine the best treatment for each patients. Another obstacle is the fact that no insurance company pays for medical marijuana. After a year of prescribing medical marijuana for patients with migraine and other painful conditions it is clear that it works for a minority of my patients. However, I prescribe it only after more traditional methods fail, so my results may not be as good as if I used medical marijuana earlier. Our standard approach involves lifestyle changes, regular exercise, dietary changes, magnesium, CoQ10, and other supplements, followed by drugs and Botox injections. These are mostly well-studied treatments and with the possible exception of drugs, should precede the use of medical marijuana. Having said that, For a few of my patients medical marijuana dramatically improved their quality of life and I am very glad that we have this treatment option available.

Dr. Rafael Mechoulam and Dr. Alexander Mauskop
May 4, 2017, NYC

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Beta-blocker propranolol (Inderal) was first approved over 50 years ago for the treatment of hypertension and 10 years later became the first drug to be approved for the prevention of migraine headaches. Beta-blockers that followed, including atenolol, timolol, nebivolol, and other, also work for the prevention of migraines. Beta-blockers are also used to treat benign essential or familial tremor, performance anxiety, and other disorders.

A study recently published in Arthritis Care and Research suggests that beta-blockers also reduce arthritis pain. The researchers evaluated 873 patients who suffered from painful osteoarthritis of the hip and/or knee as well as hypertension and who were taking at least one anti-hypertensive medication. Their analysis took into account age, gender, body mass index (BMI), knee or hip osteoarthritis, history of joint replacement, anxiety and depression. The result of this sophisticated analysis showed that patients who were taking beta-blockers had less pain than patients taking other anti-hypertensive medications. Patients taking beta-blockers were also found to be taking less of opioid (narcotic) and other prescription pain medications.

This type of study shows a correlation between the use of certain medications and pain, however to prove that beta-blockers are indeed effective for the pain of osteoarthritis or any other type of pain, we need prospective blinded studies. Until we have those kind of studies, which often take years to complete, it seems prudent to consider using beta-blockers as first-line drugs for the prevention of migraines in patients who also suffer from arthritis pain.

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Naltrexone, along with naloxone are narcotic (opioid) antidotes, that is they counteract the effect of narcotics and are used to treat overdoses with heroin, fentanyl, Percocet, Vicodin, and other opioid drugs. Surprisingly, low doses of naltrexone (LDN) seem to be effective in treating pain. LDN has been also used to treat symptom in conditions such as depression, fibromyalgia, Crohn’s disease, multiple sclerosis, complex regional pain syndrome (which used to be called reflex sympathetic dystrophy), and autoimmune disorders.

Low dose naltrexone is not a typical pain killer, but may be helping pain by reducing inflammation. Instead of opioid receptors, it works on Toll-like receptor 4 (TLR4) receptors on glial cells. Glial cells surround the nerve cells and play important functions in the brain, beyond just a supporting role that had been assigned to them for many years. Opioid drugs are known to promote inflammation through the brain immune system leading to worsening of pain over time. Recent discoveries have shown that the Toll-like receptors are involved in triggering these inflammatory immune events. These discoveries have led many researchers to look at ways to block TLR4, but so far no such drug has been developed. We do have several existing medications that seem to block TLR4. Besides LDN, amitriptyline (Elavil) and cyclobenzaprine (Flexeril) are two other drugs that block TLR4 and that have been used for years to treat pain.

No large controlled studies of LDN for migraines, pain or any other condition have been conducted to date. Despite the fact that the evidence is only anecdotal and that LDN my work purely through the placebo effect, advantages of LDN are that it is inexpensive and safe. Naltrexone is available in 25 and 50 mg tablets, while the amount used for LDN is between 1.5 to 4.5 mg. This means that it can be obtained only from a compounding pharmacy. Naltrexone is not a controlled substance, but it does require a prescription from the doctor.

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Medical marijuana was legalized in New York in February of this year. Since then, I’ve prescribed it to over 30 patients and about a third of them have found it to be effective. We are planning an observational study to determine which of the three approved types (inhaled, sublingual, oral) and what ratio of active ingredients (THC/CBD) are preferred by migraine sufferers. Doctors who prescribe medical marijuana do have to take an online training course, but the course does not teach about the optimal use because no one has researched this question. There are also regulatory issues to deal with.

Several sets of guidelines have been published by various medical organizations addressing the proper use of medical marijuana, other than dosing and route of administration. Here are some of the recommendations with my comments:

“The doctor should adhere to current standards of practice and comply with state laws, rules and regulations, which may specify conditions for which a patient may quality.”
Migraine is not one of the conditions listed specifically, but it is often accompanied by neuropathic pain, which is listed.

“The doctor’s office should not be located at a marijuana dispensary or cultivation center. The doctor should not receive financial compensation from or hold a financial interest in marijuana-related businesses or be affiliated with them in any way.”
This one is easy for us.

“The physician should not use marijuana either medicinally or recreationally while actively engaged in the practice of medicine.”
I’ve never tried it.

“There should be an established doctor-patient relationship before the doctor considers the use of medical marijuana.”
I prescribe it only to our established patients.

“The doctor should do a physical exam and gather health history, including documentation of previous therapies used by the patient and information on any personal or family history of substance abuse, mental illness or psychotic disorders. The diagnosis should justify the consideration of medical marijuana.”
All of our patients undergo a thorough evaluation.

“The doctor should review other treatment options. The known benefits and risks of marijuana should be presented, along with the warning that, unlike with FDA-approved drugs, there is variability and lack of standardization in marijuana preparation.”
We use medical marijuana only after other non-drug and drug treatments fail.

“If the medical marijuana is chosen, a specific treatment plan for a limited period of time should be agreed on, with details documented in the medical record. The doctor should instruct the patient not to drive or operate heavy machinery while using marijuana.”
Yes, I do that.

“The patient should be seen for follow-up visits to monitor for efficacy and side effects of medical marijuana.”
This is a standard practice with any treatment.

“Patients with a history of mental health problems, substance abuse or addiction should be referred for further evaluation as needed.”
I typically avoid prescribing medical marijuana to such patients.

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One of the most common problems with Botox injections given for chronic migraines is that doctors use the standard protocol without adjusting the dose. One of my patients is an 83 year old woman with chronic migraines who has done exceptionally well with Botox injections with no side effects for the past 16 years. She recently started living in Florida during the winter and had Botox injections given by a local doctor. I provided her with a copy of the injection sites and the total dose, which was 65 units given into 20 sites in the forehead and temples. Her Florida neurologist insisted on giving her the standard 31 injections with 155 units all around the head, neck and shoulders. The result was that she developed drooping of her eyelids and pain and weakness of her neck. It defies common sense to inject a small woman who weighs 90 lbs with the same amount of Botox as a 200-lbs man.

Sticking strictly to the protocol prevents many doctors from addressing clenching and grinding of the teeth (TMJ syndrome), which often worsens migraines. Injecting Botox into the masseter muscles (chewing muscles at the corner of the lower jaw) can have a dramatic effect on TMJ pain and migraines. Other patients may need additional injections into the scalp or upper back, depending on where the pain is felt. Since Botox comes only in 100 and 200 unit vials, if the insurance company approves Botox, it sends us 200 units. Instead of discarding the remaining 45 units, we usually give additional injections into the areas of pain that may not be included in the standard protocol.

Giving injections every 3 months or even every 12 weeks works well for many patients. However, about a quarter of my migraine patients find that the effect of Botox lasts only 10 weeks and in a small number , even less than 10 weeks. Fortunately, some insurance companies allow Botox to be administered every 10 weeks, but many do not. Some even limit injections to every 3 months, and not a day earlier, even though the clinical trials that led to the FDA approval involved giving injections every 12 weeks. Having a week or two of worsening migraines can eliminate the cumulative effect we see with repeated treatments. That is, each subsequent Botox treatment provides better relief than the previous one. This may not the case if headaches worsen before the next treatment is given.

Cosmetic concerns are not trivial since Botox injections can make you look strange – as if you are always surprised or look sinister with the ends of your eyebrows always lifted. This can be easily avoided by injecting a very small amount of Botox into the appropriate muscles above the ends of the eyebrows or a little beyond them. In some patients this can be predicted before the first treatment by looking at the lines seen with lifting of the eyebrows. In others, it becomes apparent only after the first treatment. If the appearance is very unappealing, we ask the patient to return to get two small additional injections for which we do not charge.

To minimize bruising and pain we use very thin needles. A 30-gauge needle is used most often, however an even thinner, 33-gauge needle is also available, but is rarely used (higher number indicates a thinner needle). We recommend using a 33-gauge needles, at least for the forehead, where injections tend to be more painful and where bruising, if it happens, is very visible.

Many dermatologists and plastic surgeons tell their patients not to bend down or do anything strenuous to avoid movement of Botox which may lead to drooping of the eyelids. There is no theoretical or practical evidence for this restriction. Once injected, Botox does not move around freely but stays in the injected area. In my 22 years of injecting Botox, I’ve treated thousands of headache sufferers and fewer than 1% of patients developed drooping eyelids and none were related to bending or any other activities. Drooping is more common in older patients, is always reversible within days or weeks, and sometimes can be relieved by eye drops (aproclonidine).

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Fibromyalgia is a condition comorbid with migraine, which means that migraine sufferers are more likely to have fibromyalgia and those with fibromyalgia are more likely to have migraines (such relationships are not always bidirectional). One common finding in these two conditions is low magnesium level and both condition often improve with magnesium supplementation or magnesium infusions.

A new study by Dr. T. Romano of 60 patients with fibromyalgia showed that those who have low red blood cell (RBC) magnesium levels are likely to have low levels of growth hormone (IGF-1, or insulin-like growth factor 1). RBC magnesium level is a more accurate test than the routine serum magnesium level, which is highly unreliable as most of the body’s magnesium sits inside the cells.

Dr. Romano recommends magnesium supplementation and a referral to an endocrinologist. It is possible that treatment with growth hormone will help those who are deficient, although it is also possible that magnesium supplementation alone (oral or intravenous, if oral is ineffective) could increase the production of growth hormone.

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Magnesium infusion given before or during surgery reduces the amount of opioid analgesics (narcotics) needed in the 24 hours following surgery. Doctors at the Saint Barnabas Medical Center in Livingston, NJ reviewed 14 of the most rigorous clinical trials which involved 910 patients. Half of those patients were given intravenous magnesium and the other half, placebo. During the first day after surgery there was a significant reduction in the need for morphine by those receiving magnesium compared with placebo.

Another study published in 2013 reviewed 20 clinical trials of magnesium for post-operative pain. These trials included 1,257 patients. This review also concluded that magnesium improved pain and reduced the need for narcotic pain killers.

Prescription narcotics are frequently in the news because of the epidemic of prescription drug abuse. However, the advantages of not using as much of these drugs after surgery are far greater than just a reduction of the risk of addiction. These drugs cause constipation, which is a problem after surgery even without opioid drugs, and it makes recovery more difficult. They can also cause confusion, difficulty breathing, and other side effects.

There are many possible explanations for the pain-relieving effects of magnesium. We know that it regulates the function of several receptors involved in pain, including serotonin and NMDA. It also relaxes muscles, opens constricted blood vessels, and reduces excitability of the brain and the entire nervous system. Both mental and physical stress depletes magnesium and they are very much present with surgery.

Magnesium is a natural pain blocker, which is effective for many patients with migraine and cluster headaches, as well as those with fibromyalgia, back pain, neuropathy, and other types of pain. Here is a recent blog post on magnesium and migraines.

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Acupuncture and Alexander technique appear to be equally effective and significantly more effective for the treatment of chronic neck pain than routine care, according to a study by British researchers published in the latest issue of the Annals of Internal Medicine.

The doctors divided 517 patients who suffered from neck pain for at least 6 years into three groups. The first group received an average of 10 50-minute acupuncture treatments, the second had an average of 14 30-minute Alexander technique lessons, and the third group received the usual care. The authors found that acupuncture and Alexander technique both led to a significant reduction in neck pain and associated disability compared with usual care at 12 months.

One possible explanation of such good efficacy beyond the direct effect of the treatments was that patients in the active treatment groups had improved self-efficacy. Self-efficacy is the belief that one’s actions are responsible for successful outcomes and it was measured by a standardized questionnaire.

It is possible that other forms of therapy that enhance self-efficacy, such as tai chi, meditation, and other can also improve long-standing neck pain, as well as headaches. There are many acupuncture studies that show a significant benefit for migraine headaches (here is one described in a previous post), however unlike this neck pain study most of them did not follow patients for such a long period of time. Alexander technique has been also helpful for some of my patients, but again, good studies are lacking.

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About 12% of the population suffers from migraines. In addition to high rates of migraine-related disability, migraineurs are at a higher risk than the general population of additional disability related to depression, anxiety, irritable bowel syndrome, fibromyalgia, and other conditions.

Fibromyalgia is a disorder of the central nervous system with increased brain excitability. It often manifests itself not only with muscle pains, but also fatigue, memory problems, and sleep and mood disturbances. Various studies estimate that anywhere from 2% to 8% of the general adult population suffers from fibromyalgia. Just like with migraine, women are more often affected than men. The likelihood of coexisting fibromyalgia increases with increasing frequency and severity of migraine attacks.

Both migraine and fibromyalgia have been individually linked with increased risk of suicide. However, it is not clear that the risk is more than additive.

A study just published in Neurology, reports that patients with migraine and coexisting fibromyalgia have a higher risk of suicidal ideation and suicide attempts compared with migraine patients without fibromyalgia.

The study looked at 1,318 patients who attended a headache clinic. Of these patients, 133 or 10% were found to also have fibromyalgia. Patients with both conditions had more frequent, more severe, and longer-lasting migraine attacks as well as higher use of abortive medications.

Compared with migraine patients who did not have fibromyalgia, those with fibromyalgia were more likely to report suicidal ideation (58% vs 24%) and suicide attempts (18% vs 6%).

This report suggests that migraine and fibromyalgia may magnify the risk of suicide compared with the risk of the individual conditions. However, because this data comes from a specialty headache clinic, many patients were severely affected by their migraines, with more than 35% having chronic migraine. It is likely that the results would be less dramatic among migraine sufferers in the general population. Almost half of the estimated 35 million migraine sufferers in the US do not consult a physician. Most of them suffer from milder migraines than those who do consult a doctor.

This study suggests that patients with migraine should be evaluated for other chronic pain conditions and for their mental health well-being. In particular, patients with chronic migraine should be screened for other painful conditions and mental illness. And patients with fibromyalgia should also be evaluated for migraine and potential suicide ideation. Patients often do not appear depressed, but simple questions can detect depression, which can lead to effective treatment. Our initial evaluation at the New York Headache Center includes two questions which are highly indicative of depression: 1. Have you been bothered a lot in the last month by feeling sad, down, or depressed? 2. Have you been bothered a lot in the last month by a loss of interest or pleasure in your daily activities?

Antidepressants have been proven to be effective for the prevention of migraines even in the absence of depression and are the best choice for people suffering from both conditions. Prozac, Lexapro and other SSRI antidepressants do not help migraines or pain, but SNRIs such as Effexor, Cymbalta, and Savella or tricyclics such as Elavil, Pamelor, and Vivactil do relieve pain and depression.

Magnesium deficiency is common in both migraines and fibromyalgia and we recommend an oral supplement to all patients. Some patients do not absorb magnesium and respond very well to monthly intravenous infusions of magnesium. Both their migraines improve as do fibromyalgia symptoms.

One interesting difference between migraines and fibromyalgia is the response to Botox. Botox is proven to be highly effective for the prevention of migraines and it works very well to relax spastic muscles. However, Botox appears to be ineffective for the treatment of muscle spasm in fibromyalgia. It is possibly explained by the fact that Botox interferes with the function of acetylcholine, a neurotransmitter involved in contracting healthy muscles. In fibromyalgia, studies suggests a deficit in acetylcholine, so further blocking it would be ineffective or even make the muscle pain worse (which I’ve seen in a few patients).

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Epidural steroid injections are popular for persistent neck and back pains. Patients with migraine and other headaches often have neck pain as well and if they happen to visit an anesthesiologist/pain specialist instead of a neurologist, there is a good chance they will be offered a cervical epidural steroid injection. If you or someone you know are offered such injections, just say no.

Despite the widespread use of this procedure, there is no good scientific evidence that these injections help. Not only they probably do not help, they can cause serious side effects. The US Food and Drug Administration (FDA) is warning that injection of corticosteroids into the epidural space of the spine may result in rare but serious adverse events, including loss of vision, stroke, paralysis, and death.

The FDA is requiring the addition of a warning to the drug labels of injectable corticosteroids to describe these risks.

The FDA said that “Injectable corticosteroids are commonly used to reduce swelling or inflammation. Injecting corticosteroids into the epidural space of the spine has been a widespread practice for many decades; however, the effectiveness and safety of the drugs for this use have not been established, and the FDA has not approved corticosteroids for such use.”

The FDA reviewed cases of serious neurological adverse events associated with epidural corticosteroid injections. Serious adverse events included death, spinal cord infarction, paraplegia, quadriplegia, cortical blindness, stroke, seizures, nerve injury, and brain edema.

Some doctors perform these injections under X-ray guidance, but even then serious neurological complications can occur. X-ray guidance also exposes patients to harmful radiation and increases the cost of the procedure, which is significant even without the X-ray.

This FDA warning is unrelated to a recent disastrous contamination of corticosteroids used for epidural injections. This contamination occurred at a compounding pharmacy in Massachusetts and resulted in 749 patients contracting fungal meningitis with 61 patients dying from it. This is another reason to avoid epidurals.

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