Approaches to improve the diagnosis and treatment of traumatic neuropathic pain

Abstract

"The most terrible of all tortures which a nerve wound may inflict.” Silas W. Mitchell, a neurologist during the American Civil War, stated in his book Injuries of Nerves and their Consequence. (1) One hundred and fifty years later, patients with a nerve injury describe their pain as "touching a cut power cord connected to the outlet." Neuropathic pain, originating from “a lesion or disease of the somatosensory nervous system”, continues to be one of the most significant challenges for the scientific community. (2) In 2017, the U.S. prevalence of neuropathic pain was 15%, and the number of people affected by this condition continues to grow. (3,4) Traumatic neuropathic pain, one condition that conforms to neuropathic pain, represents a significant cause of disability in adults, with upwards of 30% developing chronic pain with neuropathic characteristics after a peripheral nerve injury. (5,6) The physical and emotional impact is enormous, and the lost productivity value due to chronic pain is estimated to be around 300 billion dollars annually. (7–10) Traumatic neuropathic pain contributes to this economic burden by being more prevalent in middle-aged adults. (5,6) That adds up to the fact that neuropathic pain is a culture medium for opioid dependence and the public health emergency announced by the U.S. Department of Health and Human Services. In 2019, 10.1 million people misused opioid prescriptions, and 64% of the population experiencing neuropathic pain for at least three months reported opioids use, from which 20.9% correspond to potent opioids (i.e., morphine, oxycodone). (3,11)

Despite the efforts to improve the understanding of traumatic neuropathic pain conditions and the literature that reports 70-80% of pain improvement after an accurate diagnosis and surgical treatment, the results do not always translate into functional and painless recovery. (12–17) The approach to neuropathic pain has deficiencies at all stages, from its interpretation and diagnosis to its treatment. The psychosocial component of pain and the lack of tools to guide diagnosis add to pain's complexity and unclear biological bases.

We present a clinical and basic science approach to improve the accuracy of a diagnosis of traumatic neuropathic pain and explore a potential mechanism of neuropathic hypersensitivity after an injury. The first approach describes the implementation of pain sketches for assessing and interpreting pain in patients who underwent a major limb amputation and Targeted Muscle Reinnervation (TMR), a procedure to manage nerve stumps resulting from the amputation. (12–14) The second approach exposes a potential mechanism for the sensitivity that characterized the neuroma, a mass of axons, cells and fibrosis resulting from the aberrant regeneration of an injured nerve. (15)

This thesis aims to further our understanding of this problem and generate additional solutions, which could impact the medical field in a manner that will benefit patients and physicians.