Wednesday, March 24, 2010

Pain perception

Some people are stoic and some aren't. … Maybe there's a plausible biological reason for that difference.
---Dr. Geoffrey Woods, Medical geneticist, Cambridge University

My patient's face was all pinchy with pain, an expression not generally seen in a 20-something year old lady. She'd visited Walmart the previous day (an outing that always makes me pinchy with impatience as my husband meanders through every last aisle). While there, she bent over to examine some wonderful find and skewered her forehead on a metal hook.

"Ew," you're thinking, which is what I would've thought if there had been a ragged tear in her face, or any kind of mark whatsoever. Her forehead, however, was completely smooth and unblemished.

"So," I said, "where did it snag you?" And I touched the indicated spot, sending her recoiling in pain, pinchier than ever. The area wasn't red, abraded, swollen, or bruised. I told her that while I appreciated she was in a lot of pain, my examination indicated no serious injury. I then assured her that her pain should diminish greatly in the following days.

As usual, when confronted with pain reports that seem to far outstrip apparent injury, I wished I could walk a mile in her forehead. What was she really feeling in there? Real pain, real drama, a need for sympathy, worried sick, or what?

Dr. Woods and company also wondered why humans demonstrate such a wide spectrum of pain perception. They already knew from previous research that three rare mutations in the SCN9A gene are a serious problem insofar as such genetic changes can cause persons to be either too sensitive or completely oblivious to painful stimuli. In the first case, the faulty SCN9A gene allows sodium ions to flood through channels in the surface membranes of cells in the central nervous system. As a result, these neurons painfully overfire in response to minor daily occurrences such as bumping a shoulder against a wall when taking a corner too close. At the opposite extreme, SCN9A gone haywire in a different way prevents the perception of pain altogether. Affected persons, consequently, receive no signals say from a fracture or sprain and, therefore, have no cue to stop moving and get off the injured joint.

The Cambridge team went looking for subtle, more common mutations in the SCN9A gene, namely substitutions of a single nucleic protein (SNP) in the gene's sequence(1). They studied a group of subjects with osteoarthritis of comparable severity to see if these SNP variations correlated with differing levels of pain perception. One variation present in a small subset of the group was indeed associated with the highest pain perception in those who carried it. The scientists then looked in other people with other common pain syndromes such as sciatica and lumbar disk disease, again finding that "the statistical link between having the rare SNP and feeling more pain was impressively strong." In other words, those persons with lower pain thresholds were significantly more likely to have this particular SNP variant.

The researchers found that just under 20% of their subjects carried one copy of this particular SCN9A mutation, but only 2-3% had two defective copies, and these were the people most likely to react strongly to their painful conditions. Further testing suggested that this mutation renders them incapable of squeezing their sodium channels shut so wave after wave of pain news just keeps rolling in.

Obviously, this genetic test is not available for clinical use, and there's nothing to be done about it anyway. Those of us in the medical business and everyone involved in the sympathy business can now appreciate, however, that some persons are hard-wired for more pain than others; for such persons, that 'stiff upper lip' advice may be harder to follow. And my hapless Walmart shopper was back two days later, her forehead no longer tender but her head now clamped in the vise of a secondary tension type headache brought on by scrunching her brow over the original hooking.
1) Woods, GC, et al. "Pain perception is altered by a nucleotide polymorphism in SCN9A," Proceedings of the National Academy of Sciences.

Sunday, March 21, 2010

Probiotics and clostridia difficile

I noticed a disturbing item in this a.m.'s paper--diarrheal illnesses caused by clostridia difficile are increasing in number and virulence. This serious intestinal condition is now more common than disease caused by methicillin resistant staph aureus aka MRSA as a cause of serious hospital-acquired infections.

C. diff tends to be a nosocomial infection, i.e. one that results from medical treatment, specifically, in this case, from the use of potent antibiotics. C. diff is not normally present in the gastrointestinal tract but moves into the territory after antibiotics kill off the good little bacteria who normally call our colons home. Increasingly virulent strains of c. diff can cause life-threatening colitis which occasionally requires emergency surgery, sepsis (overwhelming infection), and death.

While community-acquired C. diff rarely causes serious illness, it can run on and on in unpleasant and debilitating ways. Research suggests that the use of probiotics --preparations available over-the-counter that contain live bacteria of the intestinal-friendly variety-- can decrease the risk of antibiotic-related diarrhea including C. diff. While the use of these supplements is not recommended as the sole treatment of the condition, they may in fact promote a healthier micro-environment in the colon which increases resistance to a C. diff invasion.

I often recommend probiotics to my patients starting antibiotics for acute bacterial illness. I was interested, therefore, in a recent review by Consumer Lab of the various products on the market. Consumer Lab conducts testing on various over-the-counter nutritional supplements, including a review of the scientific literature for supporting information on their legitimate uses as well as a summary of testing results for purity and truth-in-labeling. Their nominal annual fee is well worth the price for consumers interested in using such products.

In the "you can't always get what you think you do" world of label-reading, I discovered that two of the probiotic products I recommend by name--Culturelle and Align--did not deliver the promised organisms per capsule. There is quite an in-depth discussion of probiotics on this site, and I recommend it to you as vital information concerning the increasingly perilous world of microbes, anti-microbes, and the pro-microbes that defeat them.

Sunday, March 14, 2010

Cigarettes and cognition

I was just visiting Mauigirl's blog; she's been struggling with the declining health of her aging mom. Between a hospital stay followed by a move to a nursing home, MG's mom has been one month without a cigarette. MG notes that research suggests that nicotine has favorable effects on cognition and wonders if the notable change she's seen in her mom's mental functioning might be, in part, due to the lack of nicotine. I've often told my patients that people like to smoke for good reason, that, in fact, cigarettes are not only calming but wonderful for concentration and focus.

Cigarettes--or rather the nicotine within--may be neuroprotective. While I'm all in favor of saving the brain, I won't be prescribing cigarettes to anyone wishing to keep their marbles. But there's interesting evidence suggesting that nicotine is not without its benefits to brain.

Scientists have noted that persons who smoke have lower rates of neurodegenerative diseases such as Parkinson's and Alzheimer's. Korean rats were encouraged to smoke via an automatic smoking machine. After four weeks of 'automatic smoking' for ten minutes per day, the rodents were significantly protected against the seizure-inducing effects kainic acid. Apparently, if you want to dip your head in kainic acid (whatever that is), you might consider smoking too.

Kainic acid exposure aside, researchers have other theories why nicotine is good for the brain. The brain is full of nicotinic acetylcholine receptors; activation of these cellular switches has a number of beneficial actions. This effect of nicotine has been compared to "turning up the volume of a radio signal." As acetylcholinergic brain cells are in charge of memory and executive functioning--i.e. planning and carrying out complex tasks--turning up the volume is a good thing. No wonder people enjoy the clarity and focus of a Marlboro.

Neuroscientists at the University of Florida have discovered still another mechanism as to why nicotine might promote brain health. They found that nicotine prevents overactivation of little neuron-supporting cells called microglia. When the microglia get all hot and bothered with overactivation, they can set off events toxic to their neuronal buddies unto death. Well who wants that? Check out what Florida's Dr. Douglas Shytle has to say about that:

Microglia can be your best friend or your worst enemy depending on the signals they receive. The analogy is that you keep talking to them they will take care of you, but if you stop talking they are more likely to get aggressive and have a toxic effect on the brain.

If all this makes you want to take up smoking again, hang on. The Southern investigators realize that they must "now develop drugs that mimic the beneficial action of nicotine without its unwanted side effects."