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NEUROPATHIC PAIN (NP) HAS A COMPLEX, severe, and persistent character with varying intensity and duration. It may accompany many diseases but can also be related to an injury. This chapter provides an overview of NP, including the definition, history, epidemiology, and pathophysiology. Also, clinical manifestations, assessment methods, screening tests, and diagnostic tools are reviewed. The classification of NP syndromes with respect to their anatomic localization (peripheral nervous system, central nervous system, and mixed) will be investigated in detail, in addition to pharmacologic and onpharmacologic treatment options. First-line medication choice in the management of NP includes tricyclic antidepressants (TCAs), serotonin-norepinephrine reuptake inhibitors (SNRIs), anticonvulsants, opioids, cannabinoids, and topical agents.1 Physical therapy modalities such as superficial and deep heat applications, traction, laser, transcutaneous electrical nerve stimulation (TENS), and diadynamic and interferential electrical currents are more helpful when combined with therapeutic exercises. Psychotherapy, cognitive-behavioral therapy (CBT), and relaxation therapy are recommended in the management of NP. Noninvasive (repetitive transcranial magnetic stimulation [rTMS] and transcranial direct current stimulation [tDCS]) and invasive neuromodulation techniques (deep brain stimulation [DBS], motor cortex stimulation [MCS], and spinal cord stimulation [SCS]) are also focused on the treatment of NP.


The history of pain originates from the beginning of humanity. Pain has evolutionary importance and can be experienced by anyone in their lifetime because it is the most primitive warning sign of external and internal threats. Its presentation and expression can vary among different cultures, ethnics, ages, and genders. NP has been identified since 3000 BC, and was initially formally defined and characterized in the nineteenth century. In 1773, John Fothergill described trigeminal neuralgia, which is the first definition of a subtype of NP in the literature.2 Silas Weir Mitchell observed that the soldiers who had gunshot wounds during the American Civil War had permanent burning pain and defined “causalgia” in 1864.3 Paget described local paralysis and peripheral NP during the same period. The term “central pain” was first used by Edinger in 1891.4 Déjerine and Roussy described “Le syndrome thalamiqué” as severe, persistent, paroxysmal, often intolerable pain on the hemiplegic side unresponsive to all analgesic treatments for stroke patients in Paris in 1906.5 Several medications and methods emerged for the treatment of NP in the early 1900s. Bonica, the father of modern pain medicine, emphasized the importance of an multimodality and multidisciplinary approach in pain management.6

Previously, the definition of NP was “pain initiated or caused by a primary lesion, dysfunction, or transitory perturbation of the peripheral or central nervous system,” which has several missing points in order to address pathological findings.7 The definition for NP has been updated recently by the International Association for Study of Pain (IASP) as “pain arising as a direct consequence of a lesion or disease affecting the somatosensory system.”8 The two major advantages of the new definition are (1) it specifies the general term ...

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