Comments on: If graves could talk, Patrick Wall’s would be screaming (oh, and genes affect pain)

By: Neil O'Connell

Neil O'Connell — Wed, 17 Mar 2010 09:49:43 +0000

Thanks for that insight. I agree the findings are fascinating and the study appears genuinely rigorous particularly the consistency across different patient groups. It is entirely reasonable that this SNP is just part of the genetic picture and that the combined genetic influences might be predicted to be greater. I guess how much remains to be seen.

In terms of the clinical relevance it would be really exciting to look at this and the other genetic influences in a big prospective observational study to assess the influence on incidence, natural course and prognosis of painful conditions. I guess we would be talking BIG BIG numbers research.

My concern over the size of the effect really arises from the data from observational studies in back pain. Small associations seem to produce such inconsistent results in these kinds of studies.

By: Kathleen Sluka

Kathleen Sluka — Wed, 17 Mar 2010 02:46:35 +0000

Some thoughts and responses. This is an excellent paper. It shows that a relatively common mutation (SNP=single nucleotide polymorphism) in the sodium channel (NaV 1.7) gene is associated with higher pain sensitivity in several different pain conditions (OA, sciatica, phantom limb pain) and pain sensitivity in healthy controls (but not pancreatitis pain. As genetic studies go this is extremely complete and well done exmaining among several different pain conditions and healthy controls. What is really nice, is that they also examine the different SNPs on function in neurons and show that neruons with the particular SNP associated with more pain are also associated with more excitability.

To note, however, there are other genes such as COMT and serotonin transporters in the catecholamine pathways that have also been associated with more pain in some pain syndromes/conditions.

The way I interpret these types of studies is that there are several genes that might each by itself explain a portion of the pain sensitivity. There are certainly other factors, i.e. injury, personality, mental state (depression, anxiety), pain catastrophizing, fatigue, etc…. that will also explain a portion. I expect, all these variables if added together in one study would explain a greater portion of the pain sensitivity.

As stated in the article: “All such measures of pain severity (referring to self-report here) are intrinsically imprecise because they necessarily rely on subjective reporting using pain scales such as the WOMAC questionnaire or the Visual Analog Pain Scale. The consequent variability in quantifying pain is a major contributor to reducing the power of this type of study.”

The variability in pain is precisely what makes it unique to each individual. As scientists we are always trying to minimize this variability, as clinicians we try to ignore it (it is back pain, shoulder pain, osteoarthritis, etc.). However, we all need to recognize the variability if we are to find the answers to better pain management. This study begins to address a portion of the variability.

By: Lorimer

Lorimer — Tue, 16 Mar 2010 04:54:23 +0000

As ever, great observations Neil. I have almost no idea either. We need a genetics dude. Anyone out there?……

By: Neil O

Neil O — Mon, 15 Mar 2010 09:31:21 +0000

Interesting findings. As someone who knows diddly about genetics and its methods I would note that the 95% confidence intervals seem very wide for the significant results given the size of the populations studied. That may be completely normal for this kind of research. It is hard to know how clinically relevant it all is but if it was data from a treatment I would call it marginal.

Also this might be a moot point as I genuinely know nothing (really nothing at all) but is there any scope for blinding (or lack of) of those doing the genotyping to play a role?