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.

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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.

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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.

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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.

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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.

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.

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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.