Archive
Pain Research

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.

Read More

It is hard to believe the report of a group of Danish doctors who found 28 out of 61 (46%) patients undergoing surgery for a herniated lumbar disc to have a bacterial infection in those discs. Just like the idea that stomach ulcers are caused by bacteria seemed preposterous, so does the finding of bacterial infection in patients with low back pain. However, after 10 years of skepticism and ridicule Helicobacter bacteria was recognized as the cause of many stomach ulcers and the doctors who made this discovery were awarded a Nobel Prize. Another recent surprise discovery is that babies are not born sterile but are inhabited by a variety of bacteria which they obviously must have acquired from their mothers while in the uterus. This was established by examining the stool of newborns immediately after birth.

Of the 23 patients with infections 4 had more than one type of bacteria present. The most common type of infection was with Pseudomonas acnes, which does not require oxygen to grow (so called anaerobic bacterium). Most patients with infections had abnormally looking vertebral bones (bone edema), although these abnormalities were not specific, that is they can be present without an infection as well. About 6% of the general population and 35-40% of those with low back pain have these abnormal findings on an MRI scan.

In the second randomized controlled study by Dr. Albert and her colleagues treated 162 patients who had low back pain for more than 6 months, a disc herniation and bone changes on the MRI scan, but who did not undergo surgery. Half of the patients were treated for 100 days with an antibiotic, amoxicillin clavulanate (Bioclavid) and the other half with placebo. The patients taking antibiotics experienced significant improvement for a year compared with those taking placebo. Improvement included the degree of back pain, sleep quality, and disability. Antibiotic caused only mild gastrointestinal side effects.

It is premature to make any definitive conclusions before larger confirmatory studies are conducted. However, in patients with chronic back (and possibly neck) pain as well as bone edema on the MRI scan treatment with an antibiotic should be considered.

Art credit: JulieMauskop.com

Read More

Calcium inside the nerve cells (neurons) seems to be crucial in making pain chronic, according to a publication in the journal Neuron by researchers in Heidelberg, Germany. They discovered that in patients with persistent pain, calcium in the spinal cord neurons helps contact other pain-conducting neurons resulting in increased sensitivity to painful stimuli. This may explain how the pain memory is formed.

Chronic pain caused by inflammation, nerve injury, herniated disks, and other causes often leads to a persistent structural change in the nervous system. This pain often persists even after the original cause, such as a herniated disc, is removed. Many chronic pain patients including those with chronic migraine develop allodynia, an increased sensitivity which results in pain from touch and minor pressure. Migraine patients often cannot brush their hair or wear glasses because of such sensitivity. In people with chronic pain, too much calcium inside the neurons that transmit pain makes them react to activation of neurons that normally transmit sensation of touch, heat, and other non-painful sensations. This excess calcium enters the nucleus of the cell where the genetic material is located and it activates certain genes that promote pain. One of the researchers, Prof. Kuner said that “These genes regulated by calcium in the spinal cord are the key to the chronicity of pain, since they can trigger permanent changes.”

Blocking calcium in the cell seems to prevent such increased sensitivity. Mice in which the effect of the calcium in the cell nucleus is blocked did not develop hypersensitivity to painful stimuli or a pain memory despite chronic inflammation.

Interestingly, magnesium is a natural antagonist of calcium and I would speculate that its deficiency may also promote chronic pain.

Art credit: JulieMauskop.com

Read More

It is not surprising that persistent pain can cause depression, but a study just published in The Journal of Pain suggests a possible mechanism and more importantly a possible treatment. Australian doctors examined 669 patients who were over 60 years old and were seen at a pain clinic. Catastrophizing, measured by a validated scale, was a reliable predictor of depression. They showed a strong correlation between pain intensity, catastrophizing, and depression. That is, if someone tended to think thoughts such as, “I will never get better” or “I cannot go on like this” they were also more likely to be depressed. Fortunately, this kind of thinking can be changed with psychological interventions and such change usually leads to improvement in pain.

Art credit: JulieMauskop.com

Read More

Pain is defined as a negative emotional experience that is affected by a variety of psychological factors. Some of the pain brain mechanisms involve endorphins (endogenous opioids) and cannabinoids (substances related to marijuana – yes, we have those in our brains) and they have been found to be involved in stress-related and placebo pain relief. A study by Italian researchers just published in journal Pain showed that when the meaning of the pain experience is changed from negative to positive through verbal suggestions, the opioid and cannabinoid systems are co-activated and these, in turn, increase pain tolerance. Healthy volunteers had a blood pressure cuff inflated over the upper arm to the point of pain and were asked to tolerate the pain as long as possible. One group was told about the negative effects of pain. The second group was told that the the pain would be beneficial to the muscles. The second group was able to tolerate pain much longer than the first one. When the researchers gave the group with the positive message opioid antidote or the antidote to marijuana, their pain tolerance worsened. Interestingly, the combined administration of these two antidotes completely eliminated their advantage over the negative message group. This study showed that a positive approach to pain reduces the global pain experience. The authors concluded that their findings may have a profound impact on clinical practice. For example, postoperative pain, which means healing, can be perceived as less unpleasant than cancer pain, which means death. Therefore, the behavioral manipulation of the meaning of pain can represent an effective approach to pain management.
This study is complementary to the study that showed the advantages of optimistic attitude mentioned in a previous post.

Art credit: JulieMauskop.com

Read More

German researchers examined the possible connection between headaches and low back pain in a study published in the recent issue of journal Pain. They questioned 5605 headache sufferers about the frequency and type of their headaches and about the frequency of their low back pain. Of these 5605 people 255 (4.5%) had chronic headache and the rest had episodic (less than 15 headache days each month). Migraine was diagnosed in 2933 subjects, of whom 182 (6.2%) had chronic migraines. Tension-type headache was diagnosed in 1253 respondents, of whom 50 (4.0%) had chronic tension-type headaches. They also found that 6030 out of 9944 people suffered from back pains, of whom 1267 (21.0%) reported frequent low back pain. The odds of having frequent low back pain were between 2.5 times higher in all episodic headache subtypes (migraine and tension) when compared to those without any headaches. The odds of having frequent low back pain were 15 times higher in all chronic headache subtypes when compared to those without headaches. One possible explanation for this association is that having pain in any part of your body makes you more likely to develop other types of pain. We know that persistent pain makes the nervous system more excitable and this in turn may predispose to other pain syndromes. We also know that people with fibromyalgia are more likely to suffer from headaches, and those with migraines are more likely to develop painful irritable bowel syndrome.

Read More

Expectation of relief can enhance pain relief, according to a new study published in The Journal of Pain by Canadian researchers. This is not a new discovery, but provides additional confirmation of this important clinical observation. The current study was performed in 60 healthy volunteers, 15 of whom expected relief of experimental pain, 15 expected worsening of pain from the procedure, 15 had no expectations, and 15 were in a control group. Pain was induced by electrical stimulation of right leg, while applying an ice pack to the left arm (counterstimulation) was tested as a treatment to reduce pain in the leg. Those who were told that the pain will worsen from the ice pack in fact felt more pain, while those who were expecting relief, experienced less pain. A study published in 2009 by Harvard researchers showed that expectation of relief from acupuncture also translated into stronger relief experienced by volunteers subjected to experimental pain. Their clinical observation was confirmed by functional MRI scans showing stronger activation of pain relieving structures in the brain. The researchers concluded that while acupuncture provides pain relief by sending blocking messages up to the central nervous system, messages regulating pain perception from the brain down can affect pain perception depending on person’s expectations.
This suggests that having a positive expectation when seeing doctors and undergoing various treatments may improve the outcome of these treatments.

photo-4

Read More

Optimists appear to tolerate pain better than pessimists, an old discovery that is supported by a new study published in The Journal of Pain. The study by researchers at the Universities of Florida and Alabama involved 140 older individuals with osteoarthritis. They were subjected to experimental pain (heat was repeatedly applied to the forearm) and also had a variety of psychological tests. Those elderly who were judged to be optimists (based on an established and validated test) had lower pain perception. The study also showed that optimism was associated with lower levels of catastrophizing. Catastrophizing was also measured by validated scale, which includes questions such as “I feel it is never going to get better” and “I can’t stand it anymore”. The good news is that studies have shown that cognitive-behavioral therapy can reduce catastrophizing and improve pain. So, if you are a pessimist, do not give up – see a psychologist and your pain may be easier to control.


Photo credit: JulieMauskop.com

Read More

Autoimmune dysfunction can cause pain according to a study just published in Neurology by a group of Mayo Clinic researchers. Dr. CJ Klein and his colleagues examined 316 patients who had antibodies to a structure involved in various nerve functions (voltage-gated potassium channel, or VGKC) and discovered that 159 of them had pain as the initial symptoms and 45 of those had pain as the only symptom of this autoimmune reaction. In 19 of these patients pain was localized to face and head, suggesting that some of the headache patients may also suffer from this condition.
The antibodies to VGKC are known to cause excessive excitability of the nervous system. Some of the patients in the study were previously thought to have fibromyalgia (a condition known to be associated with excessive excitation of the nervous system) or psychogenic (not real) pain. This is an exciting discovery since treatment with immune therapies (such as drugs and intravenous immune globulin, or IVIG) relieved chronic pain in 81% of the Mayo Clinic patients. Epilepsy drugs can also help some of these patients.
The difficulty at this point is in identifying patients who should be tested for VGKC antibodies. Probably, we should test patients with chronic persistent pain that does not easily respond to standard treatments. Another difficulty is that the immunosuppressive drugs can have serious side effects, while IVIG is very expensive and can also cause side effects. So these therapies should be reserved for patients in whom pain causes significant disability and in whom potential benefits outweigh the potential risks.

Read More

Likeable patients may receive better care for their pain, according to a study by Belgian researchers. The researchers asked 40 doctors to look at photos of six different patients. Each photo was accompanied by a description such as friendly, egoistic, arrogant, honest, faithful, hypocritical, or reserved. Then the doctors were asked to evaluate the severity of pain in these six patients after they watched a video in which the patients were being evaluated for shoulder pain. Patients with positive descriptions were thought to have more pain than those with negative ones. Most doctors are probably convinced that they treat all patients equally, but this is clearly not true. Doctors and medical students should be informed of these findings so that they constantly remind themselves of the potential bias.

Read More

Hypertension appears to increase the risk of trigeminal neuralgia, according to a new study published in Neurology by Taiwanese researchers. They looked at 138,492 people with hypertension and compared them to 276,984 people of similar age and sex who did not have hypertension. The risk of trigeminal neuralgia was one and half times higher in those with high blood pressure. Trigeminal neuralgia is an extremely painful condition with electric-like pain in one or more branches of the trigeminal nerve, which supplies sensation to the face. The likely cause of trigeminal neuralgia is compression of the trigeminal nerve by a blood vessel at the site where the nerve is coming out of the brainstem. Persistently elevated blood pressure tends to make blood vessels harder and more tortuous. Hypertension has been show to be a factor in a similar condition – hemifacial spasm, which results from the compression of the facial nerve by a blood vessel. The usual treatment of trigeminal neuralgia starts with medications, such as oxcarbazepine (Trileptal), carbamazepine (Tegretol), phenytoin (Dilantin), baclofen (Lioresal) and other. If medications are ineffective, invasive treatments are recommended. Botox injections have been reported to provide some patients with good relief, although Botox is probably more effective for hemifacial spasm. ANother procedure is the destruction of the tigeminal nerve ganglion with heat from a radiofrequency probe. This is done under X-ray guidance. Radiofrequency ablation is often effective, but the pain may recur and the procedure may need to be repeated. A more drastic but also more effective approach involves opening the skull and placing a Teflon patch between the nerve and the offending blood vessel. Obviously, this procedure carries a higher risk of serious complications, but in experienced hands it is relatively safe. You can determine the experience of the neurosurgeon by asking how many procedure he or she has performed. Ideally, pick a surgeon who has done it hundreds of times.

Read More

At the NYHC, just like at all headache clinics, we see many patients with severe disability. A very interesting study just published in the journal Pain seems to tell us how to predict which of these disabled patients will respond to treatment. Researchers at the Ohio University compared patients whose severe disability improved with treatment and those whose did not. They carefully examined a wide variety of possible factors, including race/ethnicity (African American versus Caucasian American), psychiatric comorbidity, headache management self-efficacy, perceived social support, locus of control, number of headache diagnoses, migraine versus tension-type headache diagnosis, chronic versus episodic headache diagnosis, headache days per month, headache episode severity, and whether the patient attended all scheduled treatment appointments. The only factor that seemed to predict whose disability will improve and whose will not was the attendance of the 3 follow-up visits. Those who came for follow-up visits were much more likely to improve than those who did not – showing up is half the battle.

Read More

Botox is now approved for chronic migraine headaches. However, it may help you feel happier not only because your headaches improved. Several studies suggest that the inability to frown caused by Botox makes people happier too. Psychologists at the University of Cardiff in Wales showed that healthy people (not headache sufferers) who had cosmetic Botox injections were happier and less anxious than those who hadn’t. Another study published in the Journal of Pain showed that people who grimaced during a painful procedure felt more pain than people who did not. In an experiment by German researchers, healthy people were asked to make an angry face while their brains were being scanned by a functional MRI. Those who received Botox injections had much less activation in areas of the brain that process emotions than those who had no injections. My patients who receive Botox for headaches also report that because they cannot make an angry face they feel less angry. We need a large study of the effect of Botox injections on the mood, so that if this finding is confirmed, Botox can be recommend for the treatment of mood disorders.

Read More

Acupuncture increases connections between different areas of the brain, according to Dhond and other Korean researchers who published their findings in the journal Pain.  They compared the effect of true and sham acupuncture in healthy volunteers using functional MRI of the brain.  They discovered that true acupuncture (insertion of one needle into the forearm) enhanced the “spacial extent of resting brain networks to include anti-nociceptive (pain-relieving), memory, and affective (responsible for emotions) brain regions”.   The researchers felt that this enhancement of connections between various parts of the brain is probably responsible for the pain relief induced by acupuncture.   After the recent German study of acupuncture for headaches which involved over 15,000 patients there is little doubt that acupuncture works for headaches (and many other pain conditions), but this study helps provide stronger scientific evidence that the relief is not due to placebo.

Read More

Botulinum toxin, which most people know as Botox is produced by a bacteria – Clostridium botulinum.  This bacteria actually produces 7 different type of this toxin: A, B, C, D, E, F, and G.  Botox is botulinum toxin, type A, while another commercial product, Myobloc is botulinum toxin, type B.  Researchers, Drs. Dolly, Aoki and their colleagues managed to combine type A and E, according to a report in The Journal of Neuroscience.  Test tube experiments suggest that this combination could prove to be more effective for the treatment of pain than type A alone.  This is a very promising discovery, since Botox is effective for only about two thirds of chronic migraine sufferers.  The combined toxin could be also effective for other types of pain.

Read More

Progressive muscle relaxation is an integral part of biofeedback training, but can be used by itself for the treatment of migraine and tension-type headaches.   A group of researchers at the Ohio State University published an article in the journal Pain which reports the effect of progressive muscle relaxation on experimental pain in healthy volunteers.   A single 25-minute tape-recorded session of progressive muscle relaxation resulted in a higher pain tolerance and reduced stress from pain.  It can be safely assumed that regular practice sessions will result in even better results and all pain patients, including those with headaches should be encouraged to learn this simple technique.

Read More

A person  empathizing with someone in pain perceives his or her own pain as more severe and unpleasant.  Researchers at McGill University published these findings in the current issue of journal Pain.  This observation could explain, at least in part, high frequency of pain symptoms observed in spouses of chronic pain patients.   Even laboratory mice have heightened pain behavior when exposed to cagemates, but not to strangers, in pain.  Clearly, the thing to do is not to ignore your spouse’s or friend’s pain, but rather try to get the pain relieved.  If that is not possible, hopefully, a cognitive-behavioral psychologist may be able to devise a way to be very supportive and helpful without constantly feeling badly for the person in pain.

Read More

Patients who faced delays in the treatment of their chronic pain were found to have worsening of their condition, according to a recent review published in the journal Pain.  The review of 24 trials showed that patients had a significant deterioration of their health-related quality of life and psychological well being.  This was true for patients who waited for six or more months to receive treatment.  Studies looking at shorter wait times were less conclusive.  The authors conclude that waiting for treatment of chronic pain for six months or longer is medically unacceptable.  While our medical system is often to blame for such delays, many patients delay their treatment for a variety of other reasons as well.  It is important for friends and relatives to urge someone who suffers from chronic pain (including headaches) to seek medical attention from a qualified specialist.

Read More

Facial expression of pain seems to make you feel worse, according to a study published in the May issue of The Journal of Pain.  Healthy volunteers were asked to make a painful expression before the pain started and without anyone appearing to be watching (to avoid “social feedback”).  The pain was perceived more unpleasant when the volunteers made a painful facial expression compared to when a neutral facial expression was made.  Practical application of this study is in that people in pain should try to avoid grimacing from pain and keep their faces relaxed.  The authors discuss recent brain imaging studies which seem to confirm an old observation that facial expression can cause one to experience emotion that is being expressed.  In other words, forcing yourself to smile may improve your mood, while making an angry  face can make you feel angry.

Read More

We always recommend exercise as one of the most effective preventive treatments for migraines and tension-type headaches.  However, it appears that some patients may have difficult time exercising because of low vitamin D levels.  Vitamin D receptors are located within muscle and are important for normal muscle activity.  Michael Hooten and colleagues discovered that pain clinic patients who had low vitamin D levels had lower exercise tolerance as well as lower general health perception than patients with normal levels.  Most people are familiar with the role of vitamin D in bone health.  However, it has many other functions in the body.  In addition to exercise tolerance, another unexpected effect of vitamin D deficiency is to worsen symptoms of gastro-esophageal reflux, which causes heartburn and other symptoms.  Taking vitamin D supplements relieves reflux symptoms in some patients.  Many people are not taking sufficient amounts of vitamin D.  If deficiency is documented by a blood test, patients usually need to take 1000-2000 units a day.

Read More

It appears that women respond better to morphine than men and men respond better to a different opioid (narcotic) drug, butorphanol.  This was the conculsion of a study presented at the American Pain Society.  The next step that the researchers plan is to look at possible genetic factors which may explain this difference.  Although the study was small and needs to be confirmed, such knowledge could have an important practical impact.  Opioid drugs are rarely used for the treatment of headaches, but when necessary it would be useful to know which one has a better chance of success.

Read More

Many patients tell me that monosodium glutamate (MSG) gives them headaches, but we never had a scientific study to explain or support this observation.  A study by Brian Cairns and his colleagues in the November issue of journal Pain reveals possible mechanism by which this happens.  The researchers found that rats given MSG had an elevated level of glutamate in their muscles and that MSG made the muscles more sensitive to pressure.  Glutamate is a neurotransmitter that promotes pain transmission in the nerveous system and therefore the authors concluded that MSG could increase pain sensitivity in humans as well.  The bottom line, if you are prone to headaches or have chronic pain, stay away from MSG.

Read More

Presence of anxiety and depression (“distress”) at the time of initial diagnosis of sciatica predict worse outcome of both surgical and non-surgical treatment three years after the onset of pain according to a report in the July issue of journal Pain. Presence of anxiety and depression (“distress”) at the time of initial diagnosis of sciatica predict worse outcome of both surgical and non-surgical treatment three years after the onset of pain according to a report in the July issue of journal Pain. The authors speculate that the reason could be lower self-management efforts and maladaptive coping strategies. In fact previous studies have shown that adaptive coping skills training produces improvement in pain that lasts for months and years beyond the actual training. This training is usually performed by cognitive psychologists.

Read More