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

In 1986, Pat Wall and Steve McMahon commented on the folly of talking about nociception as though it is pain –

‘the labelling of nociceptors as pain fibres was not an admirable simplification but an unfortunate trivialization’ and

‘…pain is an integrated package of analysed results related to meaning, significance and imperative action’ [1]

Almost 25 years have passed and still this unfortunate trivialisation dominates our language when we are discussing pain.

The bee in my bonnet was most recently stirred up by a Science news article covering a new paper from a bunch of people, with Geoffrey Woods from Cambridge at the helm and Stephen Waxman’s from Yale at the rear, published in PNAS[2].  Now, I think the PNAS article itself is really hot, with the exception of the actual numbers being absolutely impossible to extract, at least for me. I can tell you what they did: they investigated DNA of almost 600 people with arthritis and found a particular gene was associated with higher pain levels. They then tested for that gene in about 200 people  with back pain and then a group with phantom limb pain. The association held.  So, I think you can be very confident, on the basis of this work, in concluding that this gene is associated with higher pain levels.

The biology makes sense too – this gene encodes for a particular type of sodium channel that is important for nociceptive peripheral neurones to work properly and complete absence of this sodium channel, which happens when the culprit gene is really stuffed up (technical term = nonsensemutation), causes the stupidly labelled ‘insensitivity to pain’ – a more accurate label would be ‘insensitivity to noxious stimuli’.  So, the biological rationale matches the association.  I think the authors are correct in predicting that this has implications for new targets for analgesia. However, before you go and buy stocks, have a look at the size of the association.  It is small. Insy winsy, teeny weeny actually.  So, surprisingly enough, this large study with almost 1000 participants, reminds us that

‘…pain is an integrated package of analysed results related to meaning, significance and imperative action’

– not simply a measure of nociception. So, my take? The PNAS paper is important and might let us better address one contributor to chronic pain states. Now, back to that bee buzzing away: Quotes from the Science news article:

  • “You’re more sensitive to pain.” This one attributed to Woods (gasp!);
  • “the sodium influx then spurs the nerve cell to send a pain message to the brain.”;
  • “can leave a person impervious to pain”;
  • “allowing a stronger pain signal to be sent to the brain”;
  • “stopping the pain signal sooner”.

AAAAAAAAAAAgh! I can not summarise it better than Wall & McMahon did, so I will iterate –

‘the labelling of nociceptors as pain fibres was not an admirable simplification but an unfortunate trivialization’.

Why is it important? Because our patients are always looking for Descartes, and here he is, in all his revolutionary glory.

References

ResearchBlogging.org[1] Wall, P., & McMahon, S. (1986). The relationship of perceived pain to afferent nerve impulses Trends in Neurosciences, 9, 254-255 DOI: 10.1016/0166-2236(86)90070-6

[2] Reimann, F., Cox, J., Belfer, I., Diatchenko, L., Zaykin, D., McHale, D., Drenth, J., Dai, F., Wheeler, J., Sanders, F., Wood, L., Wu, T., Karppinen, J., Nikolajsen, L., Mannikko, M., Max, M., Kiselycznyk, C., Poddar, M., te Morsche, R., Smith, S., Gibson, D., Kelempisioti, A., Maixner, W., Gribble, F., & Woods, C. (2010). Pain perception is altered by a nucleotide polymorphism in SCN9A Proceedings of the National Academy of Sciences DOI: 10.1073/pnas.0913181107

Abstract

Pain perception is altered by a nucleotide polymorphism in SCN9A

The gene SCN9A is responsible for three human pain disorders. Nonsense mutations cause a complete absence of pain, whereas activating mutations cause severe episodic pain in paroxysmal extreme pain disorder and primary erythermalgia. This led us to investigate whether single nucleotide polymorphisms (SNPs) in SCN9A were associated with differing pain perception in the general population. We first genotyped….

For the full paper (Open Access) see PNAS