Entrapment neuropathies: pathophysiology and pathogenesis

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Abstract

A number of theories of pathogenesis of entrapment neuropathy, due to repeated loading, have been proposed and these theories are being actively explored with animal models. Tubes placed loosely around peripheral nerves cause delayed onset, chronic pain and changes in nerve morphology including nerve sprouting. Balloons placed around or adjacent to the nerve and inflated to low pressures, rapidly produce endoneurial edema and a persistent increase in intraneural pressure. The same models demonstrate long-term changes such as demyelination and fibrosis. The applied pressure causes a decrement in nerve function and abnormal morphology in a dose-dependent manner that appears to be linked to the amount of endoneurial edema. A new model involving involuntary, repetitive fingertip loading for 6 h per week for 4 weeks has caused slowing of nerve function at the wrist similar to that seen in patients with carpal tunnel syndrome. These models have the potential to reveal the mechanisms of injury at the cellular and biochemical level and address questions about the relative importance of various biomechanical factors (e.g. peak force, mean force, force rate, duty cycle, etc.). In addition, these models will allow us to evaluate various prevention, treatment and rehabilitation protocols.

Section snippets

Human pathophysiology

Entrapment neuropathies usually occur near joints where the nerve passes through a fibrous tunnel as it courses from one body segment to the next. Examples are carpal tunnel syndrome, an injury to the median nerve at the wrist, and cubital tunnel syndrome, an injury to the ulnar nerve at the elbow. The diagnosis is easily made when the sensory and/or motor deficit corresponds to the tissues innervated by the nerve and a nerve conduction study documents conduction slowing [19]. The diagnosis is

Acute effects of compression

The effects of extraneural compression on microcirculation have been studied under a microscope while a balloon surrounding the nerve was inflated to different pressures [3], [26]. Pressures of 20–30 mmHg interfere with venous blood flow while pressures of 35–50 mmHg reduce capillary flow. A pressure of 70 mmHg causes complete ischemia.

A brief (4 h) period of low-pressure (30 mmHg), extraneural compression of the nerve, causes increased vascular permeability leading to edema formation within

Short-term compression studies

The biological effects of a brief, controlled nerve compression were studied in the rat sciatic nerve using small, inflatable cuffs [5], [20]. In 91 rats, pressures of either 0, 30 or 80 mmHg were applied for 2 h to the nerve, then the cuff was removed and the incision closed. At regular intervals up to 28 days the nerves were removed and examined for evidence of injury. Within 4 h, endoneurial edema formed within all compressed nerves and persisted for the entire time of the study.

Chronic compression models

To model chronic nerve compression, short silicon tubes have been secured loosely around the rat sciatic or sural nerve [14], [35]. Pain and nerve histologic changes occured after 1–3 months. The biological response of the nerve was similar to that found in the cuff experiments, with early perineural edema followed by a short-term macrophage recruitment, fibrosis, demyelination, and, finally, nerve fiber degeneration.

One of the limitations of the tube models is that it is not possible to

Repetitive loading model

Recently, an entrapment neuropathy model associated with repeated loading of the digits was developed using a rabbit model [24]. The goal was to develop a model in which the finger repetition rate and applied force could be precisely controlled. The model involved stimulating the flexor digitorum profundus muscle at a controlled frequency, duty cycle, and duration. The third digit was attached to a load cell and the stimulation voltage was adjusted to achieve the desired finger twitch force.

Summary

The critical compression pressures that alter blood flow in the nerve are known; effects on the venous flow are observed at pressures as low as 20 mmHg. A delayed nerve injury is observed after pressures as low as 30 mmHg are applied to the nerve for 2 h. These pressures initially cause capillary leakage, the accumulation of intra- and extra-neurial edema and a persistently increased intraneurial pressure. These initial changes are followed, over the next 30 days, by a brief inflammatory

Acknowledgements

National Institute for Occupational Safety and Health RO3 OHAR03664, RO1 OH07359; National Institutes of Health RO1 AR46174.

David Rempel is Professor of Medicine at the University of California at San Francisco, Professor of Bioengineering at UC Berkeley and director of the ergonomics graduate training program at UC Berkeley. Dr. Rempel’s research has focused on understanding mechanisms of injury to nerve and tendon due to cyclical loading and the design and evaluation of engineering interventions to prevent hand and arm disorders (e.g., tendonitis and carpal tunnel syndrome).

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  • Cited by (0)

    David Rempel is Professor of Medicine at the University of California at San Francisco, Professor of Bioengineering at UC Berkeley and director of the ergonomics graduate training program at UC Berkeley. Dr. Rempel’s research has focused on understanding mechanisms of injury to nerve and tendon due to cyclical loading and the design and evaluation of engineering interventions to prevent hand and arm disorders (e.g., tendonitis and carpal tunnel syndrome).

    Edward Diao gained a BA from Harvard College in 1977, and an MD from Columbia University in 1981. He is currently Associate Professor at the Department of Orthopaedic Surgery, University of California, San Francisco. His special interests include: hand and microvascular surgery, Flexor tendon repairs and animal model for carpal tunnel syndrome.

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