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Year : 2019  |  Volume : 67  |  Issue : 7  |  Page : 23--24

Treatment of neuropathic pain after peripheral nerve and brachial plexus traumatic injury

Daniel Umansky, Rajiv Midha 
 Department of Clinical Neurosciences and Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada

Correspondence Address:
Dr. Rajiv Midha
Department of Clinical Neurosciences and Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta

How to cite this article:
Umansky D, Midha R. Treatment of neuropathic pain after peripheral nerve and brachial plexus traumatic injury.Neurol India 2019;67:23-24

How to cite this URL:
Umansky D, Midha R. Treatment of neuropathic pain after peripheral nerve and brachial plexus traumatic injury. Neurol India [serial online] 2019 [cited 2022 Jan 17 ];67:23-24
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Full Text

The pain of the mind is worse than the pain of the body. Publilius Syrus.

Socolovsky and colleagues et al.,[1] have beautifully summarized the current status of neuropathic pain treatment along with the various types of pain associated with peripheral nerve and brachial plexus injury (BPI). They briefly describe the various mechanisms and conclude by presenting to the reader, the various possible common treatment options in greater detail. Their work is so complete that we have chosen to further elaborate herein on the authors' effort by broadening the readers' understanding of the underlying pathophysiological mechanism of neuropathic pain, as this is a topic which is reviewed to a much lesser extent in today's literature.

The main differentiation of pain types should be done while distinguishing nociceptive pain from neuropathic pain. The International Association for the Study of Pain, in its terminology section, defines pain as an unpleasant sensory and emotional experience with actual or potential damage.[2] Furthermore, 'nociceptive pain' is defined as the activation of nociceptors under threatened or actual non-neural tissue damage- that is, a normally functioning somatosensory nervous system, in contrast to the 'neuropathic pain' that occurs as a lesion or disease of the somatosensory system. Some authors emphasize the manifestation as 'spontaneous stimulus-independent pain' compared to 'stimulus-evoked pain' from alterations of sensory neurons.[3] This is an important distinction, as non-traumatic peripheral neuropathic pain may also arise from several underlying common medical conditions such as diabetic neuropathy, chemotherapy-induced polyneuropathy and postherpetic neuralgia, which are important to distinguish from the point of view of administering appropriate treatment.[4],[5]

Injured axons and cell bodies in the dorsal root ganglia (DRG) undergo intrinsic electrical excitability increase, thus spontaneously discharging impulses to the central nervous system (primary neuropathic pain signal) and maintaining central sensitization. This, in turn, is thought to amplify sensory endings in the skin and deep tissue causing tactile allodynia. In addition, this also amplifies spontaneous dysesthesia and pain.[6],[7] It is this phenomenon along with deafferentation (injury or permanent loss of primary afferent fibers) that differentiates peripheral neuropathic pain from other types of pain.[5]

Devor and Wall, in their seminal work,[7],[8],[9] presented the initial observation of peripheral nerve lesions leading to plasticity and reorganization in dorsal horn cells. An important aspect is the voltage gated sodium channel being depolarized, leading to spontaneous action potential activity, and in inappropriately high frequency, contributing to the chronic pain sensation. Following their work, more than ten different sodium channels subtypes are currently thought to be encoded by different genes, leading to the current belief of different sodium channels holding different physiological characteristics,[7],[10] thereby influencing synaptic rearrangement. The modulation of pain following the initial insult is thought to be further affected by an intracellular increase or decrease in neurotrophins, neurotransmitters and neuromodulators.[7],[10],[11],[12] Furthermore, sodium channel expression and alteration is thought to significantly contribute to the inflammatory process of chronic pain[10],[13] and peripheral sensitization, contributing to the positive sensory phenomenon of spontaneous pain, allodynia and hyperalgesia.

Dworkin et al., in their review paper,[5] propose a simplified paradigm of approach for the neuropathic pain pathway following peripheral nerve injury (PNI), where initially, the abnormally high collection of sodium channels cause ectopic discharges and primary afferent nociceptor firing, followed by loss of inhibitory neuronal activity leading to central sensitization, and by that amplifying and sustaining the normal sensory input.

The final pathophysiological mechanism and perhaps the most exciting one which should be further addressed, are the plasticity related changes taking place following BPI, which build on the mechanisms noted above. Recent work done in the field of functional imaging strongly supports cortical and subcortical neuroplasticity following PNI and the ensuing neuropathic pain is thought to be triggered by deafferentation and is related to age.[14],[15],[16] In the models of BPI, these include adaptation of cerebral plasticity,[17] decreased intracortical inhibition,[15] and later, axonal misrouting with disturbed cortical maps following nerve injury repair, when cortical areas adjacent to the injured cortical representation areas are thought to expand and occupy the previously injured site.[18] These factors operate in addition to the more extensive adaptive processes of functional reorganization for the dominant side limbs.[19],[20]

Trying to better understand the pathophysiological mechanisms involved in neuropathic pain and BPI in particular, will allow us as treating physicians to tailor our treatment options for our patients. It will also facilitate the introduction of specific pharmacological treatment modalities whenever appropriate, and consider alternative invasive or conservative approaches. In the future, further understanding of the pathophysiological mechanisms and scientific advances involved in neuropathic pain will permit us to offer novel pharmacological, rehabilitative and neuromodulation approaches.


1Lovaglio AC, Socolovsky M, Di Masi G, Bonilla G. Treatment of neuropathic pain after peripheral nerve and brachial plexus traumatic injury. Neurol India 2019;67:S32-7.
2IASP Task Force. IASP Taxonomy. Classification of Chronic Pain, Second Edition (Revised). Descriptions of Chronic Pain Syndromes and Definitions of Pain Terms 2012; Available from: https://www.iasp [Last accesed on 2018 Nov 10].
3Clifford J Woolf RJ. Neuropathic pain: Aetiology, symptoms, mechanisms, and management. Lancet 1999; 353:1959-64.
4Nicholson B. Differential diagnosis: Nociceptive and neuropathic pain. Am J Manag Care 2006;12:256-62.
5Dworkin RH, Backonja M, Rowbotham MC, Allen RR, Argoff CR, Bennett GJ, et al. Advances in Neuropathic Pain. Arch Neurol 2003; 60:1524-34.
6Sukhotinsky I, Ben-Dor E, Raber P, Devor M. Key role of the dorsal root ganglion in neuropathic tactile hypersensibility. Eur J Pain 2004;8:135-43.
7Devor M. Sodium channels and mechanisms of neuropathic pain. J Pain 2006;7: S3-S12.
8Devor M, Wall PD. Reorganisation of spinal cord sensory map after peripheral nerve injury. Nature 1978; 276:75-6.
9Wall PD, Devor M. The effect of peripheral nerve injury on dorsal root potentials and on transmission of afferent signals into the spinal cord. Brain Res 1981;20:95-111.
10Waxman SG, Cummins TR, Dib-Hajj SD, Black JA. Voltage-gated sodium channels and the molecular pathogenesis of pain: A review. J Rehabil Res Dev 2000;37:517-28.
11Aguayo LG, White G. Effects of nerve growth factor on TTX- and capsaicin-sensitivity in adult rat sensory neurons. Brain Res 1992; 570:61-7.
12Liu CN, Wall PD, Ben-Dor E, Michaelis M, Amir R, Devor M. Tactile allodynia in the absence of C-fiber activation: Altered firing properties of DRG neurons following spinal nerve injury. Pain 2000;85:503-21.
13Tanaka M, Cummins TR, Ishikawa K, Dib-Hajj SD, Black JA, Waxman SG. SNS Na+ channel expression increases in dorsal root ganglion neurons in the carrageenan inflammatory pain model. Neuroreport 1998;9:967-72.
14Lundborg G. Nerve injury and repair-A challenge to the plastic brain. J Peripher Nerv Syst 2003; 8:209-26.
15Simon NG, Franz CK, Gupta N, Alden T, Kliot M. Central adaptation following brachial plexus injury. World Neurosurg 2016;85:325-32.
16Socolovsky M, Malessy M, Lopez D, Guedes F, Flores L. Current concepts in plasticity and nerve transfers: Relationship between surgical techniques and outcomes. Neurosurg Focus 2017;42:E13.
17Li T, Hua XY, Zheng MX, Wang WW, Xu JG, Gu YD, et al. Different cerebral plasticity of intrinsic and extrinsic hand muscles after peripheral neurotization in a patient with brachial plexus injury: A TMS and fMRI study. Neurosci Lett 2015;604:140-4.
18Lundborg G, Rosén B. Hand function after nerve repair. Acta Physiol 2007;189:207-17.
19Feng JT, Liu HQ, Xu JG, Gu YD, Shen YD. Differences in brain adaptive functional reorganization in right and left total brachial plexus injury patients. World Neurosurg 2015; 84:702-8.
20Mohanty CB, Midha R. Nerve section causes brain reaction. World Neurosurg 2015;84,4:886-8.