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Pain

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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More patients with fibromyalgia suffer from migraine headaches than those without this fibromyalgia. Those with fibromyalgia are also more likely to have irritable bowel syndrome, depression, and panic attacks. Fibromyalgia has been a mysterious and an ill-defined condition. However, after years of research specific criteria for the diagnosis were developed and several drugs for fibromyalgia were approved by the FDA (Lyrica, Cymbalta, Savella).

A new study by researchers at the Massachusetts General Hospital suggests that half of the patients with symptoms of fibromyalgia have damaged peripheral nerves, a condition called small-fiber neuropathy. They compared skin biopsies (a test to diagnose the neuropathy) in 25 patients with fibromyalgia and 29 healthy controls. In healthy controls only 17% had neuropathy. This type of neuropathy can also occur in diabetics, but none of the 25 patients in the study had diabetes. Other conditions that can cause small-fiber neuropathy are cancer, autoimmune conditions, various toxins, vitamin B12 deficiency, and genetic disorders, but none of these were present either, except for possibly genetic cause since three patients were related (a mother and two daughters).

The practical importance of this finding is that sometimes neuropathy responds to immune therapies, such as intravenous gamma globulin.

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Female pelvic/genital pain is more common in women with chronic Headache, according to a study presented by Canadian neurologists.
The study was carried out by researchers and clinicians at the Wasser Pain Management Centre, Mount Sinai Hospital and the Centre for Headache at Womens College Hospital in Toronto, Canada. During the study period, every adult English speaking female patient at the Centre for Headache at WCH was asked if they would consent to complete a specifically devised questionnaire. Of the 72 completed questionnaires, 32 (44%) of patients reported that they had pelvic region or genital pain brought on by sexual activity. Thirteen (18%) admitted to having pelvic pain that prevents them from engaging in sexual activity. 46% of these women had not had treatment, 39% were currently being treated, and 15% said they had received treatment in the past. All but one said that she would be interested in receiving treatment if available. The researchers concluded that it is important to ask women with chronic headache about sexual pain and, if present, be able to offer a management option.

Art credit: JulieMauskop.com

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Abuse of prescription narcotic (opioid) drugs is growing at an alarming rate and they are responsible for tens of thousands of deaths due to overdose every year. While all such drugs can cause addiction, there appears to be a difference among these drugs. A study recently published in The Journal of Pain suggests that a new opioid pain killer, tapentadol (Nucynta) is less likely to cause addiction than oxycodone (Percocet, Percodan, Endocet). The study was conducted by the manufacturer of Nucynta, a subsidiary of Johnson & Johnson. The researchers looked at the risk of shopping behavior (going to more than one doctor to obtain prescriptions) in over 150,000 patients. People who were prescribed oxycodone were four times more likely to be doctor shoppers than those who were prescribed tapentadol. Also, 28% of those prescribed oxycodone were asking only for oxycodone, while only 0.6% of those prescribed tapentadole were asking for tapentadol. This means that of those prescribed tapentadol less than one percent were asking only for tapentadole and the rest asked for other narcotics. Tapentadol has another advantage in that it causes less nausea and constipation than other opioid drugs.

Abuse potential is also reduced by making the pill temper resistant. About two years ago Oxycontin, which is one of the most popular (and most abused) long-acting narcotic pain killers was reformulated to make it difficult to crush. Because Oxycontin is a long-acting drug and does not give a quick high, addicts usually crush the tablet and inject or snort it. The new formulation prevents it from being crushed and in the past two years the abuse (and the sales) of Oxycontin has dropped. The FDA recently denied permission to sell generic versions of Oxycontin because they did not have such temper-resistant properties.

Unlike with other types of pain, opioid drugs seem to be less effective in the treatment of migraine and other headaches. Headache patients often report little relief from these drugs, as well as side effects, such as nausea and sedation. Opioid analgesics, such as codeine, hydrocodone (Vicodin), oxycodone (Percocet), and other can actually make headache worse in some patients by causing rebound, or medication overuse headaches. However, there are exceptions to this rule and a very small number of our patients respond only to opioid drugs and a few are doing well with daily long-acting narcotics. To make sure these drugs are not being abused we carefully select and closely monitor such patients.

Photo credit: JulieMauskop.com

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