Mechanisms of Action of Dorsal Root Ganglion Stimulation

Abstract

The dorsal root ganglion (DRG) serves as a pivotal site for managing chronic pain through dorsal root ganglion stimulation (DRG-S). In recent years, the DRG-S has emerged as an attractive modality in the armamentarium of neuromodulation therapy due to its accessibility and efficacy in alleviating chronic pain refractory to conventional treatments. Despite its therapeutic advantages, the precise mechanisms underlying DRG-S-induced analgesia remain elusive, attributed in part to the diverse sensory neuron population within the DRG and its modulation of both peripheral and central sensory processing pathways. Emerging evidence suggests that DRG-S may alleviate pain by several mechanisms, including the reduction of nociceptive signals at the T-junction of sensory neurons, modulation of pain gating pathways within the dorsal horn, and regulation of neuronal excitability within the DRG itself. However, elucidating the full extent of DRG-S mechanisms necessitates further exploration, particularly regarding its supraspinal effects and its interactions with cognitive and affective networks. Understanding these mechanisms is crucial for optimizing neurostimulation technologies and improving clinical outcomes of DRG-S for chronic pain management. This review provides a comprehensive overview of the DRG anatomy, mechanisms of action of the DRG-S, and its significance in neuromodulation therapy for chronic pain.

A Narrative Review of the Dorsal Root Ganglia and Spinal Cord Mechanisms of Action of Neuromodulation Therapies in Neuropathic Pain

“…DRG neurons are pseudo-unipolar cells that bridge the gap between peripheral tissues and the spinal cord, delivering their products through their two nerve endings, with implications in both the PNS and CNS [ 59 , 60 ]. Using a model of tibial nerve injury in rats and DRG stimulation at the L 4 level, replicating a clinically used load (20 Hz, 150-ms pulse width, current at 80% of motor threshold), it was shown that cold and mechanical hyperalgesia and allodynia were reduced [ 61 ].…”

“…DRG neuromodulation therapy emerged later than traditional SCS as an alternative approach. DRG stimulation is effective across a range of frequencies, with 20 Hz being the default frequency [ 59 ]. In one of the first clinical trials evaluating DRG stimulation for the management of neuropathic pain, the patient population presented with neuropathies associated with intractable pain in the back and lower limbs.…”

“…( A ) (A1) Ectopic action potentials are generated through an increase in synaptic transmission between nociceptive neurons and spinal neurons [ 43 ]. ( B ) (B1) Taken together, the increased expression of voltage-gated sodium channels (VGSC; Nav.1.7, Nav 1.8, and NaV1.9) [ 53 , 54 , 55 , 56 ], calcium channels (Cav), potassium channels (TREK and TRAAK), cyclic nucleotide gated channels (HCN) [ 57 , 58 , 59 , 60 ], and transient receptor potential (TRP; TRPV1) [ 61 , 62 ] also contribute to the generation of ectopic action potentials. (B2) Plastic changes in nociceptor neurons, including the enhanced expression and activity of these channels, facilitate the generation of action potentials, resulting in neuronal sensitization [ 63 , 64 ].…”