Reappraising entrapment neuropathies: Mechanisms, diagnosis and management   May 9th, 2016

Traditionally the clinical manifestation of entrapment neuropathies (e.g., carpal tunnel syndrome, cervical and lumbar radiculopathy) is considered to be driven by local mechanisms and signs and symptoms should follow a clear anatomical pattern limited to the structures innervated by the affected peripheral nerve, or restricted to the corresponding dermatome, myotome and sclerotome.

In "Applying Modern Pain Neuroscience in Clinical Practice: Criteria for the Classification of Central Sensitization Pain” Nijs et al. (2014) wrote that β€œthe location of pain and sensory dysfunction are crucial for the differential classification between neuropathic and non-neuropathic central sensitization (CS) pain. While in neuropathic pain the location of the sensory dysfunction should be neuroanatomically logical, in non-neuropathic CS pain it should be spread in non-segmentally related areas of the body. In fact, clinical examination in non-neuropathic CS pain typically reveals increased sensitivity at sites segmentally unrelated to the primary source of nociception".

The article of Schmid et al. 2013 challenges the differential classification between neuropathic and non-neuropathic patients as seen by Jo Nijs et al., more specifically criteria 4 and 6. Also in the article of Freynhagen et al. 2008, data suggest that the symptoms and signs of either pseudo-radiculopathy or radiculopathy patients reflect more of a disease continuum rather than different disease entities.

According to Schmid et al., the diagnosis of entrapment neuropathies is complex and difficult because signs and symptoms often do not follow textbook descriptions and vary between patients with the same diagnosis. In many neuropathies widespread and contralateral symptoms are observed. Even motor deficits can occur outside the distribution of the affected nerve.

This because many of these signs and symptoms may be attributed to pathological processes proximal to the lesion site, such as, in the dorsal root ganglion, in the spinal cord or at subcortical or cortical levels. Local mechanisms like intraneural ischemia, intraneural oedema formation, Schwann cell reaction and demyelination or ectopic impulse generation may not explain most of the extra-territorial symptoms.

Neuroinflammation in the dorsal root ganglia (DRG) is a more plausibel explanation for the clinically observed spread of symptoms to extraterritorial areas. Given the close proximity of cell bodies from different peripheral nerves within the DRG, neuroinflammation around affected DRG neurons may alter the firing threshold of adjacent intact neurons originating from different sites.

Neuroinflammation also occurs at the level of the spinal cord. T-lymphocytes and glial cells start to release various inflammatory mediators. Since incoming primary afferents ascend or descend several segments when entering the spinal cord before they synapse in the dorsal horn, an inflammatory response in the spinal cord may also lower the firing thresholds of sensory fires in a multi-segmental manner.

Interestingly, neuroinflammation after severe unilateral peripheral nerve injury also occurs in the DRGs and spinal cord on the contralateral side.

There is also preliminary evidence that severe peripheral nerve injury induce glial reaction in higher pain centers, such as in the midbrain or the thalamus. Changes at these sites could explain widespread symptoms, even in another quadrant.

Clinical tests and technical investigations are described that may identify these underlying mechanisms if interpreted in the context of gain or loss of function. Gain of function, such as paraesthesia, spontaneous pain, hyperalgesia and allodynia reflects abnormal excitability or reduced inhibition of the nervous system. Loss of function, such as hypoesthesia or anesthesia indicates reduced impulse conduction along the nervous system.

Tests identifying gain of function in the affected nerve territory, but most importantly in extraterritorial areas, have therefore the potential to identify these remote mechanisms in the DRG or central nervous system.

The management of neuropathies remains challenging. Common treatment strategies such as joint mobilization, neurodynamic exercises, education and medication are discussed in terms of their potential to influence certain mechanisms at the site of the nerve injury or in the central nervous system.

A better understanding of the mechanisms involved in each patient may ultimately result in a more targeted therapeutic approach.

Luc Vanderweeen

Master of Science in Spinal Manual Therapy

Member of the Pain in Motion Research Group

Voluntary Research Fellow Vrije Universiteit Brussel

Private Practice for Spinal Manual Therapy,

Schepdaal-Dilbeek, Belgium

www.lucvanderweeen.com

2015 Pain in Motion

References and further reading:

Reappraising entrapment neuropathies – mechanisms, diagnosis and management. Schmid AB, Nee RJ, Coppieters MW. Manual Therapy 2013 Dec; 18(6):449-57

http://www.ncbi.nlm.nih.gov/pubmed/24008054

Applying modern pain neuroscience in clinical practice: criteria for the classification of central sensitization pain. Nijs J, Torres-Cueco R, van Wilgen CP, Girbes EL, Struyf F, Roussel N, van Oosterwijck J, Daenen L, Kuppens K, Vanderweeen L, Hermans L, Beckwee D, Voogt L, Clark J, Moloney N, Meeus M. Pain Physician 2014 Sep-Oct;17(5):447-57

http://www.ncbi.nlm.nih.gov/pubmed/25247901

Pseudoradicular and Radicular Low-Back Pain -- A Disease Continuum Rather than Different Entities? Answers from Quantitative Sensory Testing. Freynhagen R, et al. Pain 2008. March Vol. 135. No. 1-2. Pp. 65-74

http://www.ncbi.nlm.nih.gov/pubmed/17570589

Low back pain: guidelines for the clinical classification of predominant neuropathic, nociceptive, or central sensitization pain. Nijs J, Apeldoorn A, Hallegraeff H, Clark J, Smeets R, Malfliet A, Girbes EL, De Kooning M, Ickmans K. Pain Physician. 2015 May-Jun;18(3):E333-46

http://www.ncbi.nlm.nih.gov/pubmed/17570589