Lumbar radiculopathy and its neurobiological basis

Abstract

Lumbar radiculopathy, a group of diseases in which the dorsal root ganglia (DRG) or dorsal roots are adversely affected by herniated discs or spinal stenosis, are clinically characterized by spontaneous and evoked types of pain. The pain is underpinned by various distinct pathophysiological mechanisms in the peripheral and central nervous systems. However, the diagnosis of lumbar radiculopathy is still unsatisfactory, because the association of the pain with the neurobiological basis of radiculopathy is largely unknown. Several animal models used to explore the underlying neurobiological basis of lumbar radiculopathy could be classified as mechanical, chemical, or both based on the component of injury. Mechanical injury elevates the intraneural pressure, reduces blood flow, and eventually establishes ischemia in the dorsal root and the DRG. Ischemia may induce ischemic pain and cause nerve damage or death, and the subsequent nerve damage or death may induce neuropathic pain. Chemical injury predominately induces inflammation surrounding the dorsal roots or DRG and consequent inflammatory mediators cause inflammatory pain. Furthermore, DRG neurons sensitized by inflammatory mediators are hypersensitive to innocuous mechanical force (stretch or compression) and responsible for mechanical allodynia in radiculopathy. As well, central sensitization in the spinal cord may play an important role in pain generation in lumbar radiculopathy. Increasing knowledge of pain-generating mechanisms and their translation into clinical symptoms and signs might allow for dissecting the mechanisms that operate in each patient. With precise clinical phenotypic characterization of lumbar radiculopathy and its connection to a specific underlying mechanism, we should be able to design optimal treatments for individuals. This review discusses the present knowledge of lumbar radiculopathy and proposes a novel mechanism-based classification.

Keywords: Low back pain, Acid-sensing ion channel, Dorsal root, Dorsal root ganglia, Disc herniation, Lumbar spine

Core tip: Lumbar radiculopathy is the most common form of neuropathic pain. However, the diagnosis of lumbar radiculopathy is still not satisfactory because of the largely unknown neurobiological basis of neuropathic pain and paresthesia. Accumulating evidence has shown that lumbar radiculopathy is a multi-factor disease and may involve almost all types of pain, including ischemic, inflammatory, mechanical, and neuropathic pain. Ion channels such as Acid-sensing ion channel 3, Piezo2 and transient receptor potential vanilloid receptor 1 responding to tissue acidosis, mechanical force, and inflammatory mediators may be the pathways transducing the pain.