More Neuroscience from the "Ortho Guy"

Well the semester is finally over. Man I never thought there would be so much to my neuroscience course. It has been an eye opening process that has improved my clinical reasoning and given me a few extra tools in my therapeutic box!

I thought I might take the next few weeks to share some of the topics discussed this semester. On the surface, some of th issues related to neuroscience seem only peripherally related to orthopedic practice. Upon further review, many hit really close to home for many of my patients. I hope you will find them as interesting as I have.

Neuropathic Pain
The mechanisms of peripheral neuropathic pain have been identified more clearly in recent years. Despite the increased understanding, neuropathic pain presents a challenge diagnostically and remains an inadequately treated clinical problem. The current review by Baron outlines evidence to support four likely mechanisms for neuropathic pain followed by a symptom-based classification system. Evidence from both animal and clinical investigations are presented in the review that add strength to the proposed mechanisms. The treatise of the review is that understanding the mechanisms and symptoms of neuropathic pain will provide a clearer path to effectively managing this disorder.

Proposed Mechanisms of Neuropathic Pain
Four potential physiologic mechanisms can explain neuropathic pain. The most peripheral mechanism involves the abnormal sensitization of primary nociceptive (Aδ and C) fibers. A possible mechanism for ectopic firing of primary afferent fibers is an upregulation of sodium ion channels at various points along the axon. Areas of focal upregulation could predispose the neuron to ectopic antidromic and orthodromic impulses. Sensitization of primary fibers has been observed in both animal and human models and is proposed to be a potential cause for heat and mechanical hyperalgesia.

A second mechanism of neuropathic pain is sympathetic sensitization of primary afferent fibers. A normal primary afferent is not sensitive to catecholamines and should not respond to changes in sympathetic activity. However, animal models have demonstrated that injured afferent nerves develop sensitivity to noradrenergic sensitivity. This sympathetic sensitization of the peripheral nerve may take place along the distal branch of the nerve or even at the dorsal ganglion.

The third potential mechanism for neuropathic pain is local inflammation of the periperhal nerve itself. The nerve supply of the peripheral nerve itself is an often underappreciated anatomical an d clinical entity. The nervi nervorum are fine afferent fibers that can communicate noxious activity along the peripheral nerve itself. As such, pain from the nervous connective tissue must also be considered as a potential source for neuropathic pain. As with sympathetic sensitization of the nerve, peripheral nerve inflammation can occur along the distal branch or the dorsal ganglion.

The fourth and final mechanism is central sensitization in the dorsal horn of the spinal cord. Repetitive simulation of primary afferents can result in progressive upregulation of post-synaptic NMDA receptors in the dorsal horn. Under prolonged stimulation, the receptive fields of dorsal horn neurons expand to include Aβ low-threshold mechanoreceptors. This creates potential for mechanoreceptor activity to trigger pain signaling neurons in the dorsal horn; a phenomenon recognized as dynamic mechanical allodynia. Additional mechanisms for mechanical allodynia are proposed including injury-induced C-fiber degeneration and reorganization in the dorsal horn. The mechanisms of central sensitization have been demonstrated in both animal and clinical investigation.

The author utilizes the preceding mechanisms to propose a symptom-based classification system for neuropathic pain to include:

• Static mechanical allodynia - gentle static pressure evokes pain
• Punctuate mechanical allodynia - normally stinging but not painful stimuli evokes pain (Von Frey hair)
• Dynamic mechanical allodynia - gentle moving stimuli at the skin evokes pain
• Cold allodynia/hyperalgesia - duh!
• Temporal summation - repetitive application of the same painful stimuli worsens symptoms
• Sympathetically maintained hyperalgesia - difficult to assess, but improves with sympathetic blockade

These criteria can be used by the clinician to more precisely describe the underlying physiology of the neuropathic event and possibly lead to more effective management strategies.

Clinical Relevance to the Physical Therapist

Traditional symptom-based classification systems have focused on nociceptive or tissue-based models of pain. The present review offers a neurophysiologic dimension to the assessment of the patients’ pain experience. If this classification system can be validated, more specific treatment approaches can be designed. The classification system may have particular relevance for the practicing physical therapist. Physical therapists are able to modulate input, processing, and output paradigms of the human nervous system through movement. As movement involves activation of both ascending and descending pathways, it is likely to have some role in modulating one or more of the mechanisms underlying neuropathic pain.

It is sometimes difficult for me to wrap my head around some of the issues related to pain. However, I've always wondered why a seemingly homogenous population of patients (say post-op TKA) have such varied therapeutic courses. Of course there are the biomechanical factors that are often very intuitive, but there must be something to account for all the variations we see! A better understanding of these mechanisms may help us identify the patients at risk from deteriorating into a more involved pain state and get them back on their feet more quickly.

Baron, R (2000). Peripheral Neuropathic Pain: From Mechanisms to Symptoms Clinical Journal of Pain, 16, 12-20