Targeting dorsal root ganglia for chemotherapy-induced peripheral neuropathy: from bench to bedside

Abstract

Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating condition affecting an increasing number of cancer survivors worldwide. However, insights into its pathophysiology and availability of effective therapies remain lacking. Dorsal root ganglia (DRG) have been studied as a key component of chemotherapeutic drug toxicity and a potential therapeutic target for CIPN treatment. This comprehensive review aims to synthesize, summarize, and correlate the results of both preclinical and clinical studies relevant to the pathophysiology and management of CIPN in relation to the DRG. Design: Review. A thorough literature search was conducted using the terms 'dorsal root ganglion' and 'chemotherapy-induced peripheral neuropathy', along with appropriate variations. Searched databases included PubMed, EMBASE, Medline, Cochrane Library, Wiley Library, and Web of Science. Inclusion criteria targeted all English language, peer-reviewed original research from the inception of these databases to the present year. Review articles, book chapters, and other nonoriginal publications were excluded. Of 134 relevant studies identified, the majority were preclinical studies elucidating how various chemotherapeutic agents, especially taxanes, disrupt neurotransmission, inflammatory processes, and apoptotic pathways within sensory neurons of DRG. Not only do these effects correlate with the presentation of CIPN, but their disruption has also been shown to reduce CIPN symptoms in preclinical models. However, clinical studies addressing DRG interventions are very limited in number and scope at this time. These results reveal various pathways within DRG that may be effective targets for CIPN treatment. While limited, clinical studies do offer promise in the utility of DRG neuromodulation in managing painful CIPN. In the future, clinical trials are needed to assess interventions aimed at these neuronal and nonneuronal pathological targets to better treat this complex condition.

Keywords: chemotherapy; dorsal root ganglia; management; neuromodulation; neuropathy; pathophysiology; stimulation.

Figure 1.

Chemotherapeutic insults affect sensory transmission through the dorsal root ganglia of the spinal cord through the involvement of microglia and immune cells, as well as the modification of various ion channels and inflammatory pathways. Neuronal damage is indicated by the red lightning strike. Proinflammatory processes are shown in red and anti-inflammatory processes are in green. ROS, reactive oxygen species; TLR4, Toll-like receptor 4; TNF-α, tumor necrosis factor alpha.

Figure 2.

This flow diagram details our search strategy. *Records were excluded if they were not in English, not peer-reviewed, not original research (e.g. reviews), or not focusing on DRG as a primary target of toxicity or treatment in the context of CIPN. CIPN, chemotherapy-induced peripheral neuropathy; DRG, dorsal root ganglia.