Pattern Identified on fMRI May Rationalize Pain Research

Apr 15, 2013

A series of studies using functional MRI have identified brain-signal patterns specific for pain that are attenuated by opioids: Also last week: top rheumatology findings of 2012, more on TNF inhibitors and cancer, and concerns about vitamin D.

Last week's articles on rheumatology topics in the major nonspecialty journals


An fMRI-Based Neurologic Signature of Physical PainN Engl J Med, April 11, 2013. Full text $15

Editorial: Pain, Heat, and Emotion with Functional MRIN Engl J Med, April 11, 2013. Full text $15

NOW@NEJM: Measuring Pain using Functional MRIN Engl J Med, April 10, 2013 (Free)

Four functional magnetic resonance imaging (fMRI) studies with 114 participants developed a pattern (signature) to measure pain produced by heat on the subject’s forearm. The first study used machine learning to derive a pattern of signals associated with pain that identified current pain, but not similar non-painful stimuli, with 93% sensitivity and specificity. The second study showed that the signature distinguished between painful heat and non-painful warmth. The third showed that the signature distinguished between physical pain and social pain (viewing an image of a romantic partner who had broken up with the subject). The fourth study showed that the signature was reduced by an opioid (remifentanil).

The editorial observes two possible outcomes of this line of research: fMRI studies may lead to an objective measure for pain, or pain may ultimately remain a subjective perception that only the patient can report. This study was limited by the low fMRI resolution, which makes it hard to identify brain structures, it observes, and the researchers assessed only skin pain, and only acute pain.

A blog on NEJM's website (the third article above) questions whether the results pertain to the forearm only or will be shown to reflect other kinds of pain.

Rheumatology research update

Update in Rheumatology: Evidence Published in 2012 Ann Intern Med., April 11, 2013, online first (Full text $20)

The choices by Atul Deodhar MD of Oregon Health Sciences University for important and promising 2012 findings that should affect practice or lead to larger-scale trials are:

(1) The Janus kinas (JAK) inhibitor tofacitinib is effective against rheumatoid arthritis (RA), but serious infections and costs are a concern.

(2) Rituximab was so clearly effective for hepatitis C-associated cryoglobulinemic vasculitis that the investigators stopped one trial. Adverse effects were low.

(3) In a Danish population-based study of patients who had a myocardial infarction, those on non-steroidal anti-inflammatory drugs (NSAIDs) were more likely to die after five years, but the results may be due to confounding factors. Naproxen had the lowest risk. (The American College of Rheumatology recommends cautious use; the American Heart Association discourages NSAIDs.)

(4) Tumor necrosis factor (TNF) inhibitors were not associated with overall cancer in a meta-analysis of registry data, but there were weaker associations with skin cancers, including melanoma.

(5) In patients with autoimmune disease, procalcitonin can distinguish bacterial infection from disease flare with sensitivity of 0.75 and specificity of 0.90, which makes it a useful adjunct to other assessments.

(6) The new ACR treatment recommendations for hip, knee and hand osteoarthritis emphasize nonpharmacologic treatment, but many of them are based merely on consensus of opinion.

(7) The new ACR treatment recommendations for gout recommend starting with NSAIDs, colchicine or corticosteroids, and address the newer agents without specific recommendations. These guidelines should allow internists to treat most gout patients without referrals to rheumatologists.

TNF inhibitors and Cancer

Rheumatoid arthritis, anti-tumour necrosis factor therapy, and risk of malignant melanoma: nationwide population based prospective cohort study from SwedenBritish Medical Journal, April 8, 2013 (Free full text)

In a large cohort study, RA patients treated with TNF inhibitors were not at increased overall risk for cancer. They did have a 50% increased relative risk, but low absolute risk, of invasive melanoma. This small absolute risk will not shift the risk-benefit balance of TNF inhibitors except for patients at high risk of melanoma.

Vitamin D dosing

Over-the-Counter and Compounded Vitamin D: Is Potency What We Expect?JAMA Intern Med. April 8, 2013 (Full text $30)

A Kaiser Permanente study previously found that only one-third of compounded vitamin D3 (cholecalciferol) supplements met USP standards (90-110% of active ingredient) for compounded pills. Now, a study of over-the-counter (OTC) cholecalciferol supplements found that two-thirds of OTC supplements met USB standards (90-120% of stated dose) for OTC pills. The one USP-verified manufacturer was highly accurate. Lack of accuracy may not harm most consumers, but may affect dose adjustments and harm women with severe deficiency, and may threaten the validity of vitamin D trials. (The U.S. Preventive Services Task Force has recommended against calcium and vitamin D supplementation in postmenopausal women to reduce fracture risk, citing no evidence of benefit and risk of kidney stones.