**16. The future of neuropathic pain management correlating symptoms to mechanism**

Limited efficacy of current pain treatment options has necessitated a revaluation of the standard classification of neuropathic pain in clinical practice [17] [31, 75-77]. It has been suggested that within etiology based neuropathic pain syndromes there are distinct subgroups of patients who experience similar "symptom constellations" representing distinct pathophy‐ siological mechanisms [95]. Furthermore, these symptom constellations can be seen, albeit in different proportions, across neuropathic pain syndromes, suggesting that the same underly‐ ing mechanism can cause neuropathic pain within and apart from the initiating etiology. Hypothetically, with this understanding comes an approach of targeted treatment that aims to identify the pathophysiological mechanism and specifically inhibit, block, or enhance the offending molecules. To implement this type of treatment will require a more intimate understanding of the mechanisms of neuropathic pain and the corresponding symptom manifestations. As this becomes defined, specific treatments can begin to emerge, and clinical trials can test the efficacy of this approach. See Table 2 for examples.

intravenous Ca2+ and Mg2+ may be effective at preventing CIPN caused a commonly used

The use of alternative and complementary medicine is on the rise, particularly in the United States [90]. Although anecdotal evidence abounds, there are relatively few RCTs supporting the use of such therapies. It is important in considering these treatments, however, that the lack of evidence is not read as evidence of lacking efficacy. The scarcity of well controlled, robust clinical trials considering non-pharmacological treatments of chronic pain makes it difficult to recommend or dismiss these alternative treatments. A few studies have examined the use of acupuncture, herbal therapy, massage, hypnosis, and biofeedback on easing chronic pain but have yielded mixed results (for a review see [90]). The difficulty in standardizing treatment, inherent to these multi-faceted approaches, is a major obstacle in drawing reliable conclusions. Additionally, small sample sizes and lack of obvious controls are also significant barriers. Despite these hurdles, which obscure evidence-based conclusions, non-pharmaco‐ logical treatments are often prescribed in conjunction with evidence-based recommendations

Deep brain stimulation, a neurosurgical technique by which an implanted electrode delivers controlled electrical impulses to targeted brain regions, has demonstrated some efficacy in treating chronic pain but is not routinely employed due to a high risk-to-benefit ratio [91]. Targeting the periventricular/periaqueductal gray, internal capsule, and sensory thalamus has demonstrated efficacy in various pain conditions [91], but not all types of chronic pain are responsive. An intriguing new target, the NAc, has recently emerged as a potential site for deep brain stimulation as it has demonstrated efficacy in a case study of post-stroke pain [92]. As studies of pain processing in the brain have suggested, the pattern of activity in the NAc is divergent in nociceptive and chronic pain representation, validating this structure as a possible

Another type of electro-stimulation device is emerging as a promising therapeutic tool for the treatment of neuropathic pain [93, 94]. Delivering repeated pulses of electrical stimulation trans-cutaneously, termed Scrambler therapy, has demonstrated some efficacy with lasting effects in CIPN [94], postsurgical pain, PHN, and spinal canal stenosis [93]. With few adverse effects and low associated risk, this may be a viable alternative to pharmacological treatment.

**16. The future of neuropathic pain management correlating symptoms to**

Limited efficacy of current pain treatment options has necessitated a revaluation of the standard classification of neuropathic pain in clinical practice [17] [31, 75-77]. It has been suggested that within etiology based neuropathic pain syndromes there are distinct subgroups

chemotherapeutic, oxaliplatin, without attenuating its antineoplastic efficacy [9].

16 Peripheral Neuropathy - A New Insight into the Mechanism, Evaluation and Management of a Complex Disorder

**15. Non-pharmacological treatment of neuropathic pain**

due to low risk of accompanying adverse effects.

therapeutic target [69].

**mechanism**


**Table 2.** Hypothetical examples of how signs and symptoms obtained in a bedside examination might indicate underlying pathophysiological mechanism. Once a putative mechanism has been established there is a potential for selective and specifically targeted treatments to be applied. For a comprehensive review see [21].
