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Pain

Many studies have shown that virtual reality experience can relieve pain. The first such study in burn patients was published 20 years ago. A comprehensive review of this topic, Immersive Virtual Reality and Virtual Embodiment for Pain Relief was published last year by Italian researchers.

A different group of Italian researchers tested the effects of visual distraction on pain in chronic migraine patients. They compared a classical hospital waiting room with an ideal room with a sea view. Both were represented in virtual reality (VR). They measured pain and brain responses induced by painful laser stimuli in healthy volunteers and patients with chronic migraine. Pain was induced in the hand of sixteen chronic migraine patients and 16 healthy controls. This was done during a fully immersive VR experience, where two types of waiting rooms were simulated. Patients with migraine showed a reduction of laser pain rating and brain responses during the sea view simulation. Control subjects experienced the same level of pain in both types of simulated rooms.

An older study of 30 patients with chronic pain showed that 20 patients had pain relief during a VR session. Ten of them reported complete pain relief. Of the 20 who had relief, 10 had continued relief after the VR session.

A combination of VR with biofeedback resulted in lasting benefits in 9 of 10 children with chronic headaches who completed 10 training sessions.

About 5% to 10% of people who try VR get cybersickness. This is a feeling of dizziness or vertigo, similar to motion sickness. This is why VR sessions are often limited to a maximum of 30 minutes.

It appears that there are several possible approaches to the treatment of pain using VR. One is by using VR for distraction. Another, by utilizing VR to facilitate biofeedback, which is proven to relieve migraine and tension headaches. The third way, yet to be proven, is by altering body perception.

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Tramadol (Ultram) is a mild narcotic (opioid) pain killer. Just like other opioids it is not a good choice to treat an acute migraine attack. Besides its addiction potential, it does not work well for most migraine patients, can cause nausea, and can lead to rebound or medication overuse headaches.

Tramadol is also available in combination with acetaminophen (Ultracet). This combination was tested in a study published in Headache, Tramadol/Acetaminophen for the Treatment of Acute Migraine Pain: Findings of a Randomized, Placebo-Controlled Trial. 305 patients took tramadol/APAP (75 mg/650 mg) or placebo for a typical migraine with moderate or severe pain.

Subjects in the tramadol/APAP group were more likely than those in the placebo group to be pain-free at 2 hours (22% vs. 9%), 6 hours (43% vs. 25%), and 24 hours (53% vs. 38%)
Side effects caused by the active drug included nausea, dizziness, vomiting, and somnolence.

Tramadol alone or in combination with acetaminophen is worth trying only if the first-line classes of drugs are ineffective or contraindicated. These include NSAIDs, triptans, and gepants.

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Cannabis has known anti-inflammatory properties. A group of researchers from UCSD published a study, Recent cannabis use in HIV is associated with reduced inflammatory markers in CSF and blood. They measured a variety of inflammation markers in the blood and cerebrospinal fluid (CSF) of people with HIV.

They showed that “Recent cannabis use was associated with lower levels of inflammatory biomarkers, both in CSF and blood, but in different patterns. These results are consistent with compartmentalization of immune effects of cannabis. The principal active components of cannabis are highly lipid soluble and sequestered in brain tissue; thus, our findings are consistent with specific anti-neuroinflammatory effects that may benefit HIV neurologic dysfunction.”

Translating this into English, smoking pot reduces inflammation not only in the body but also in the brain. Not all substances reach the brain because of the so-called blood-brain barrier. But the two main ingredients of marijuana – THC and CBD – easily dissolve in fat which allows their entry into the brain.

Obviously, not all of the effects of marijuana are beneficial. The most harmful is the inhalation of smoke which causes lung damage. Vaping medical-grade marijuana or taking it by mouth is much safer.

I’ve been prescribing medical marijuana for the past 6 years since it became legal in NY. In NY patients have a choice of capsules taken by mouth, tincture drops placed under the tongue, or vaping. I find it particularly useful for symptoms associated with migraines more than the actual pain – nausea, anxiety, and insomnia. For some, it relieves pain as well.

Marijuana seems particularly effective for pain in the elderly. One of the most dramatic responses I’ve observed was in a 95-year-old woman with severe arthritis pain. She was mentally sharp but upset about her inability to go outside and get around on her own. A small amount of marijuana produced a greater than 80% reduction in her pain. The anti-inflammatory effect of cannabis reported in the current paper could be the explanation of why it works better for arthritis pain than migraines. Inflammation does occur during a migraine process but to a lesser degree and of a different type than in arthritis.

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Naltrexone is similar to naloxone, a drug used to reverse the effect of narcotic (opioid) overdose. Naltrexone is not used to reverse the effect of an overdose, but to treat opioid and alcohol dependence. (LDN) and is given as a monthly injection or a daily pill. Naltrexone blocks the body’s own endogenous morphine (endorphin) receptors. In theory, this should make the pain worse. However, low-dose naltrexone (LDN) seems to have the opposite effect. It is possibly explained by the fact that a small amount of naltrexone blocks the endorphin receptors for a short time, during which the body begins to make more endorphins in an attempt to overcome this block. After the effect of naltrexone wears off, this extra amount of endorphins provides relief of pain and by blocking other receptors (such as Toll-like receptor 4) and reducing inflammation, potentially produces other beneficial effects, most of which are not scientifically proven.

Inflammatory bowel disease (Crohn’s disease and ulcerative colitis) do seem to respond to LDN.

A study of 27 patients with chronic central pain syndromes at the Stanford Pain Management Clinic published in The Journal of Pain concluded that “The significant findings of decreased average pain scores and depression and improved physical function after prescribing this well-tolerated, inexpensive medication provides justification for larger, controlled trials in patients with central sensitivity syndromes.” Some of these central sensitivity syndromes include migraine, fibromyalgia, irritable bowel syndrome, chronic back pain, and other.

Naltrexone is available only in a 50-mg tablet, while LDN is started at 1.5 mg nightly for a week, then 3 mg nightly for a week, and then, 4.5 mg nightly. This regimen requires a compounding pharmacy to make capsules containing 1.5 mg for the first two weeks and then, capsules with 4.5 mg. Some of my patients went up as high as 9 mg nightly. Compounded drugs tend to be more expensive than factory-made generics but because naltrexone itself is cheap, the cost of 30 capsules can be as low as $50.

Because the dose is low, side effects are rare. These include vivid dreams and insomnia and if these occur, the medicine can be taken in the morning.

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Having given Botox injections to thousands of patients, I know that some patients tolerate pain better if they curse during the procedure.

A British psychologist Richard Stephens seems to have made a career out of studying the effect of cursing on pain. His first paper Swearing as a response to pain, appeared in 2009 in NeuroReport. It showed that swearing improves pain tolerance in volunteers whose hand was submerged in icy water. His next paper, which I mentioned in a post in 2011, Swearing as a Response to Pain—Effect of Daily Swearing Frequency was published in The Journal of Pain.

In this study, Stephens looked at the effect of repeated daily swearing on experimental pain. The volunteers were again subjected to pain by submerging their hand into icy water. And they again showed that swearing reduces pain. However, people who tended to swear frequently throughout the day had less of a pain-relieving effect than those who did not.

His latest paper, Swearing as a Response to Pain: Assessing Hypoalgesic Effects of Novel “Swear” Words, was just published in the Frontiers in Psychology. The authors show that made-up “swear” words are not as effective as the good old four-letter f-word.

The conclusion of this 6,500-word research paper suggests that there is still a lot more swearing …er … I mean, studying to be done on this subject. Whether this is a good use of the British taxpayers’ money is another matter. Is the ultimate goal to save the British National Health Service money by replacing pain medications with scientifically validated swear words?

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It is not surprising that when a doctor is tired or hurried he or she is more likely to make a mistake. A new study published in JAMA Network Open provides some hard data on doctor performance as it relates to the prescribing of opioid (narcotic) analgesics. Opioids are still overprescribed, especially for migraine headache patients.

The researchers at the University of Minnesota discovered that doctors were 33% more likely to prescribe an opioid pain medicine at the end of the workday than in the beginning. If the doctor was running an hour or more behind schedule her or she was 17% more likely to prescribe an opioid. Prescribing of nonsteroidal anti-inflammatory drugs and referral to physical therapy did not display similar patterns. This was a very large study which means that the results are likely to be reliable. The study looked at 5,603 primary care practitioners who were involved in 678,319 primary care encounters for a painful condition.

Prescribing an opioid seems like a quick fix for a problem that saves doctors time, but usually is not be the best treatment for the patient.

Nobel Prize winner Daniel Kahneman in his book, Thinking Fast and Slow suggests that there are additional and easily correctable factors that may be contributing to poor decision making. Here are some quotes from the book.

“The most surprising discovery made by Baumeister’s group shows, as he puts it, that the idea of mental energy is more than a mere metaphor. The nervous system consumes more glucose than most other parts of the body, and effortful mental activity appears to be especially expensive in the currency of glucose. When you are actively involved in difficult cognitive reasoning or engaged in a task that requires self-control, your blood glucose level drops.

The bold implication of this idea is that the effects of ego depletion could be undone by ingesting glucose, and Baumeister and his colleagues have confirmed this hypothesis in several experiments… Restoring the level of available sugar in the brain had prevented the deterioration of performance.

A disturbing demonstration of depletion effects in judgment was recently reported in the Proceedings of the National Academy of Sciences. The unwitting participants in the study were eight parole judges in Israel. They spend entire days reviewing applications for parole. The cases are presented in random order, and the judges spend little time on each one, an average of 6 minutes. (The default decision is denial of parole; only 35% of requests are approved. The exact time of each decision is recorded, and the times of the judges’ three food breaks—morning break, lunch, and afternoon break—during the day are recorded as well.) The authors of the study plotted the proportion of approved requests against the time since the last food break. The proportion spikes after each meal, when about 65% of requests are granted. During the two hours or so until the judges’ next feeding, the approval rate drops steadily, to about zero just before the meal. As you might expect, this is an unwelcome result and the authors carefully checked many alternative explanations. The best possible account of the data provides bad news: tired and hungry judges tend to fall back on the easier default position of denying requests for parole. Both fatigue and hunger probably play a role.”

So for best results you may want to try to see your doctor right after lunch and hope that he or she had time to eat lunch.

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We’ve been prescribing medical marijuana for migraines and other painful conditions since it was legalized in the state of New York four years ago. While it does not seem to help most of our patients, it does benefit a significant minority. The benefits may include relief of pain, nausea, anxiety, and improved sleep. Various ratios of tetrahydrocannabinol (THC) and cannabidiol (CBD) produce different effects and often neither one alone is as effective as a combination of the two (so called entourage effect). Although marijuana is a very effective medicine for some patients, there is no good science to explain how it works, in what combination of ingredients and for what types of pain.

A very interesting study that sheds some light on the possible mechanism of action of THC was just published in a leading neurology journal, Neurology by Israeli researchers. They enrolled fifteen patients with chronic neuropathic pain in the leg (like sciatica) in a double-blind placebo-controlled crossover study. Nine patients were given THC in the first part of the study and placebo in the second and six were given placebo first and then THC. In addition to measuring the effect of THC on pain the researchers performed functional MRI (fMRI) scans before and after administering THC or placebo.

THC was significantly better than placebo at relieving pain and the fMRI scans showed THC-induced changes in the way pain may be processed in our brains. They found that THC produced a reduction in functional connectivity between the anterior cingulate cortex (ACC), a major pain-processing region that is rich in cannabinoid receptors and the sensorimotor cortex. This reduction correlated with the reduction in the subjective pain ratings after THC treatment, meaning that patients who did not have pain relief usually did not have a decrease in the connectivity between the two regions.

The study also showed that pretreatment functional connectivity between the ACC and the sensorimotor cortex positively correlated with the improvement in pain scores induced by THC, that is, the higher the positive functional connectivity at baseline, the more benefit was gained from THC administration.

The authors also commented that THC combined with CBD may have stronger pain-relieving properties. Hopefully, the researchers will figure out the best combination of THC and CBD, but it is possible that other ingredients in marijuana contribute to the therapeutic effects. This could be why some of our patients prefer products from one dispensary and not the other and why some find that the whole plant is more effective than THC with CBD in any ratio. Most patients also find that products made from different strains of marijuana plant (sativa vs indica) have different effects.

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Almost everyone has an occasional pain in the upper back and shoulders, often caused by prolonged sitting in front of a computer or just by stress. The pain is due to muscle spasm and keeping those muscles in good shape helps prevent this problem. It also helps to be aware of your body through regular meditation practice or Awareness Through Movement method developed by an Israeli physicist Moshe Feldenkrais. I’ve posted Feldenkrais exercise videos for neck pain here and here. Most people are shocked at the immediate improvement in the range of movements they notice even after the first set of exercises.

I recently had a tight knot in one of my shoulders which did not go away after 90 minutes of hot yoga. Lying on the floor at the end of the yoga session I did a 5-minute Feldenkrais exercise which made the knot melt away. In this video I demonstrate this exercise that relaxes tight muscles and stops shoulder and upper back pain. Instead of watching the video you can follow these written instructions:

Lie down on your back with a thin pillow or a soft pad under your head. Spend a minute paying attention to spots where your head, shoulders, back, arms and legs touch the ground. Then, bend your knees and keep your feet flat on the floor. Stretch your arms in front of you and put your palms together with your arms forming a tall triangle. Keep your eyes on the thumbs and slowly lift the right shoulder off the ground with your head rolling to the left. Press down the left foot to make the movement easier. Keep the shoulder lift small to avoid straining and time it with exhalation. Repeat this shoulder lift and head turn five times while maintaining the gaze on the thumbs. Then, do another five of these movements in exactly the same way, except now move your eyes from the thumbs as far as you can in the opposite direction from the head roll. It may be difficult at first because your head may want to move with the eyes. When you come back to the midline, your eyes return to the thumbs. Put your arms and legs down and again spend a minute noticing the areas of pressure where various parts of your body touch the floor. Now, repeat the same two sets of 5 movements to the left side and then rest for a minute to feel your body contact the floor.
Try to maintain regular slow breathing throughout this exercise.

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Medical marijuana appears to be very effective for the treatment of pain, according to a new study just published in the European Journal of Internal Medicine.

The study was conducted by researchers at the Soroka University Medical Center, Ben-Gurion University of the Negev, in Be’er-Sheva, Israel. Israeli scientists have been at the forefront of the research of medical applications of cannabis, starting with the discovery of THC in 1964 by a Hebrew University professor Raphael Meshulam.

In the current study, the researchers evaluated 2736 patients above 65 years of age who received medical cannabis from January 2015 to October 2017 in a specialized medical cannabis clinic. The mean age was 74 years. The most common indications for cannabis treatment were pain (67%) and cancer (61%). After six months of treatment, 94% of the respondents reported improvement in their condition and the reported pain level was reduced from a median of 8 on a scale of 0-10 to a median of 4. Most common adverse events were dizziness (9.7%) and dry mouth (7.1%). After six months, 18.1% stopped using opioid (narcotic) analgesics or reduced their dose.

The authors concluded that “the therapeutic use of cannabis is safe and efficacious in the elderly population. Cannabis use may decrease the use of other prescription medicines, including opioids.” Even though it was a very large study, it was an observational study with its obvious limitations. They also stressed the need for double-blind prospective trials to confirm the safety and efficacy of medical cannabis for the treatment of pain in the elderly.

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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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