Dorsal Root Ganglion Stimulation for Chronic Pain: Hypothesized Mechanisms of Action.

Dorsal root ganglion stimulation (DRGS) is a neuromodulation therapy for chronic pain that is refractory to conventional medical management. Currently, the mechanisms of action of DRGS-induced pain relief are unknown, precluding both our understanding of why DRGS fails to provide pain relief to some patients and the design of neurostimulation technologies that directly target these mechanisms to maximize pain relief in all patients. Due to the heterogeneity of sensory neurons in the dorsal root ganglion (DRG), the analgesic mechanisms could be attributed to the modulation of one or many cell types within the DRG and the numerous brain regions that process sensory information. Here, we summarize the leading hypotheses of the mechanisms of DRGS-induced analgesia, and propose areas of future study that will be vital to improving the clinical implementation of DRGS. PERSPECTIVE: This article synthesizes the evidence supporting the current hypotheses of the mechanisms of action of DRGS for chronic pain and suggests avenues for future interdisciplinary research which will be critical to fully elucidate the analgesic mechanisms of the therapy.

Bilateral Contralaterally Controlled Functional Electrical Stimulation Reveals New Insights Into the Interhemispheric Competition Model in Chronic Stroke.

Background. Upper-limb chronic stroke hemiplegia was once thought to persist because of disproportionate amounts of inhibition imposed from the contralesional on the ipsilesional hemisphere. Thus, one rehabilitation strategy involves discouraging engagement of the contralesional hemisphere by only engaging the impaired upper limb with intensive unilateral activities. However, this premise has recently been debated and has been shown to be task specific and/or apply only to a subset of the stroke population. Bilateral rehabilitation, conversely, engages both hemispheres and has been shown to benefit motor recovery. To determine what neurophysiological strategies bilateral therapies may engage, we compared the effects of a bilateral and unilateral based therapy using transcranial magnetic stimulation. Methods. We adopted a peripheral electrical stimulation paradigm where participants received 1 session of bilateral contralaterally controlled functional electrical stimulation (CCFES) and 1 session of unilateral cyclic neuromuscular electrical stimulation (cNMES) in a repeated-measures design. In all, 15 chronic stroke participants with a wide range of motor impairments (upper extremity Fugl-Meyer score: 15 [severe] to 63 [mild]) underwent single 1-hour sessions of CCFES and cNMES. We measured whether CCFES and cNMES produced different effects on interhemispheric inhibition (IHI) to the ipsilesional hemisphere, ipsilesional corticospinal output, and ipsilateral corticospinal output originating from the contralesional hemisphere. Results. CCFES reduced IHI and maintained ipsilesional output when compared with cNMES. We found no effect on ipsilateral output for either condition. Finally, the less-impaired participants demonstrated a greater increase in ipsilesional output following CCFES. Conclusions. Our results suggest that bilateral therapies are capable of alleviating inhibition on the ipsilesional hemisphere and enhancing output to the paretic limb.

Tailoring Brain Stimulation to the Nature of Rehabilitative Therapies in Stroke: A Conceptual Framework Based on their Unique Mechanisms of Recovery.

Despite showing early promise, several recent clinical trials of noninvasive brain stimulation (NIBS) failed to augment rehabilitative outcomes of the paretic upper limb. This article addresses why pairing NIBS with unilateral approaches is weakly generalizable to patients in all ranges of impairments. The article also addresses whether alternate therapies are better suited for the more impaired patients, where they may be more feasible and offer neurophysiologic advantages not offered with unilateral therapies. The article concludes by providing insight on how to create NIBS paradigms that are tailored to distinctly augment the effects of therapies across patients with varying degrees of impairment.

Stimulation targeting higher motor areas in stroke rehabilitation: A proof-of-concept, randomized, double-blinded placebo-controlled study of effectiveness and underlying mechanisms.

PURPOSE: To demonstrate, in a proof-of-concept study, whether potentiating ipsilesional higher motor areas (premotor cortex and supplementary motor area) augments and accelerates recovery associated with constraint induced movement. METHODS: In a randomized, double-blinded pilot clinical study, 12 patients with chronic stroke were assigned to receive anodal transcranial direct current stimulation (tDCS) (n = 6) or sham (n = 6) to the ipsilesional higher motor areas during constraint-induced movement therapy. We assessed functional and neurophysiologic outcomes before and after 5 weeks of therapy. RESULTS: Only patients receiving tDCS demonstrated gains in function and dexterity. Gains were accompanied by an increase in excitability of the contralesional rather than the ipsilesional hemisphere. CONCLUSIONS: Our proof-of-concept study provides early evidence that stimulating higher motor areas can help recruit the contralesional hemisphere in an adaptive role in cases of greater ipsilesional injury. Whether this early evidence of promise translates to remarkable gains in functional recovery compared to existing approaches of stimulation remains to be confirmed in large-scale clinical studies that can reasonably dissociate stimulation of higher motor areas from that of the traditional primary motor cortices.

Staggered transverse tripoles with quadripolar lateral anodes using percutaneous and surgical leads in spinal cord stimulation.

BACKGROUND: In spinal cord stimulation for low-back pain, the use of electrode arrays with both low-power requirements and selective activation of target dorsal column (DC) fibers is desired. The aligned transverse tripolar lead configuration offers the best DC selectivity. Electrode alignment of the same configuration using 3 parallel percutaneous leads is possible, but compromised by longitudinal migration, resulting in loss of DC selectivity. This loss might be repaired by using the adjacent anodal contacts on the lateral leads. OBJECTIVE: To investigate if stimulation using adjacent anodal contacts on the lateral percutaneous leads of a staggered transverse tripole can restore DC selectivity. METHODS: Staggered transverse tripoles with quadripolar lateral anodes were modeled on the low-thoracic vertebral region (T10-T12) of the spinal cord using (a) percutaneous lead with staggered quadripolar lateral anodal configuration (PERC QD) and (b) laminotomy lead with staggered quadripolar lateral anodal configuration (LAM QD), of the same contact dimensions. The commercially available LAM 565 surgical lead with 16 widely spaced contacts was also modeled. For comparison with PERC QD, staggered transverse tripoles with dual lateral anodes were modeled by using percutaneous lead with staggered dual lateral anodal configuration (PERC ST). RESULTS: The PERC QD improved the depth of DC penetration and enabled selective recruitment of DCs in comparison with PERC ST. Mediolateral selectivity of DCs could not be achieved with the LAM 565. CONCLUSION: Stimulation using PERC QD improves anodal shielding of dorsal roots and restores DC selectivity. Based on our modeling study, we hypothesize that, in clinical practice, LAM QD can provide an improved performance compared with the PERC QD. Our model also predicts that the same configuration realized on the commercial LAM 565 surgical lead with widely spaced contacts cannot selectively stimulate DCs essential in treating low-back pain.

Triple leads programmed to perform as longitudinal guarded cathodes in spinal cord stimulation: a modeling study.

OBJECTIVE: In spinal cord stimulation, neurosurgeons increasingly tend to implant dual leads. Dual leads (longitudinal bipole/tripole) provide medio-lateral control over the recruited dorsal column (DC) area by steering the injected cathodal currents. However, the DC recruited area is suboptimal when dual aligned leads straddling the midline programmed as longitudinal guarded cathodes (+-+) are used instead of a single lead placed over the spinal cord midline with the same configuration. As a potential improvement, an additional third lead between the two aligned leads is modeled to maximize the medio-lateral extent of the DCs at the low-thoracic vertebral region (T10-T12). METHODS AND MATERIALS: The University of Twente Spinal Cord Stimulation software (UT-SCS) is used in this modeling study. Longitudinal guarded cathodes were modeled on the low-thoracic vertebral region (T10-T12) using percutaneous triple lead configurations. The central lead was modeled over the spinal cord midline and the two lateral leads were modeled at several transverse distances to the midline lead. Medio-lateral field steering was performed with the midline lead and the second lead on each side to achieve constant anodal current ratios and variable anodal current ratios. RESULTS: Reducing the transverse lead separation resulted in increasing the depths and widths of the recruited DC area. The triple lead configuration with the least transverse separation had the largest DC recruited area and usage range. The maximum DC recruited area (in terms of both depth and width) was always found to be larger under variable anodal current ratio than constant anodal current ratio conditions. CONCLUSIONS: Triple leads programmed to perform as longitudinal guarded cathodes provide more postoperative flexibility than single and dual leads in covering a larger width of the low-thoracic DCs. The transverse separation between the leads is a major determinant of the area and distribution of paresthesia.