A theory of CTS causation

We can propose the following outline of how 'idiopathic' CTS develops:

Some individuals are are more genetically predisposed to develop CTS than others. This genetic prediposition may take the form of biochemical variation - a propensity to respond briskly with a release of the cytokines IL-6, VEGF and PG-e2 when tissues are rendered hypoxic, or a congenitally narrow tunnel, or large tendons/muscles - or any combination of these.

The initial trigger factor is raised pressure in the carpal tunnel caused by ordinary use of the hand. Flexion or extension of the wrist and strenuous hand grip are all known to increase carpal tunnel pressure in normal wrists. The raised pressure temporarily impairs blood flow in the tunnel tissues and IL-6, VEGF and PG-e2 are released from the small vessels. It is important to realise that this is a normal, and usually helpful response. If a tissue is short of oxygen then these molecules have the effect of building it a better blood supply. In most anatomical locations there is physical room for an increase in the amount of tissue but in the carpal tunnel this is not the case and the result of the attempt to improve oxygenation is an increase in carpal tunnel pressure and further interference with blood supply - establishing a vicious circle.... and there we have CTS.

This model of causation is consistent with many observed facts about CTS:

  • It provides a mechanism by which use of the hand can be a factor in the development of the disease without being the sole cause.
  • It explains the observed cases of spontaneous resolution and good results in some cases from simple measures such as rest or splinting the wrist. If the positive feedback loop can be interrupted before the formation of fibrous tissue and capillary proliferation has produced a permanent increase in tissue mass in the tunnel then the process is clearly reversible. Injected and endogenous steroid hormones are known to have a profound short term effect on CTS and are also known to suppress IL-6, VEGF and PG-e2 release as well as tending to produce atrophy of fibrous tissue.
  • Obesity is known to affect the bioavailability of sex steroids thus providing a possible mechanism by which obesity can predispose to CTS without there actually being fat deposition within the tunnel.
  • The fact that the increased pressure results, not from swelling of one obvious structure within the tunnel, but from a diffuse increase in the connective tissue which is distributed through many of the carpal tunnel tissues would explain why it has been so difficult to demonstrate enlargement of any single structure.
  • Variations in the biochemistry may help to explain some of the variability in symptoms between patients. In some individuals pain is a more prominent feature than in others and it may be that this is connected with differing levels of PG-e2 which is known to act as a pain sensitiser.

In this last respect it is especially interesting that the one structure in the carpal tunnel which definitely gets bigger in CTS patients is the median nerve itself which becomes expanded over a length not only within the carpal tunnel but also several centimetres proximal and distal to it (Nakamichi 2000). This fact has been obscured for many years by surgical observations at carpal tunnel decompression which have always emphasised thinning of the nerve within the carpal tunnel. It is only with the advent of high resolution imaging with MRI or ultrasound that it has become apparent that, in comparison to normal median nerves, the nerves of CTS patients are actually larger. The apparent thinning under the ligament is only relative to the greater swelling proximal and distal to it. There are few satisfactory histological studies of the nerve because the nerve itself is of course never removed at surgery and the microscopic nature of the swelling remains uncertain. 

Revision date - 5th December 2011

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