Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating and painful condition in patients who have received chemotherapy. The role of neuromodulation therapy in treating pain and improving neurological function in CIPN remains unclear and warrants evidence appraisal. In compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we performed a systematic review to assess change in pain intensity and neurological function after implementation of any neuromodulation intervention for CIPN. Neuromodulation interventions consisted of dorsal column spinal cord stimulation (SCS), dorsal root ganglion stimulation (DRG-S), or peripheral nerve stimulation (PNS). In total, 15 studies utilized SCS (16 participants), 7 studies utilized DRG-S (7 participants), and 1 study utilized PNS (50 participants). Per the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) criteria, there was very low-quality GRADE evidence supporting that dorsal column SCS, DRG-S, and PNS are associated with a reduction in pain severity from CIPN. Results on changes in neurological function remained equivocal due to mixed study findings on thermal sensory thresholds and touch sensation or discrimination. Future prospective, well-powered, and comparative studies assessing neuromodulation for CIPN are warranted.

Peripheral nerve stimulation (PNS) has been utilized for over 50 years with accumulating evidence of efficacy in a variety of chronic pain conditions. The level and strength of evidence supporting the use of PNS for peripheral neuropathic pain remains unclear. The purpose of this review is to synthesize data from prospective studies on the efficacy of PNS for neuropathic pain as it pertains to pain intensity, neurological deficits/neuropathy (e.g., weakness, sensory deficits, gait/balance), and other secondary outcomes (quality of life, satisfaction, emotional functioning, and adverse events). In compliance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines, this review identified articles from MEDLINE(R), EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus. Overall, per the Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria, pooled results demonstrate very low quality or low quality of evidence supporting modest to substantial improvement in pain and neurological function after PNS implantation for treatment of peripheral neuropathic pain. PNS for phantom limb pain was the only indication that had moderate level evidence. Future prospective and well-powered studies are warranted to assess the efficacy of PNS for peripheral neuropathic pain.

While denervation can occur with aging, peripheral nerve injuries are debilitating and often leads to a loss of function and neuropathic pain. Although injured peripheral nerves can regenerate and reinnervate their targets, this process is slow and directionless. There is some evidence supporting the use of neuromodulation to enhance the regeneration of peripheral nerves. This systematic review reported on the underlying mechanisms that allow neuromodulation to aid peripheral nerve regeneration and highlighted important in vivo studies that demonstrate its efficacy. Studies were identified from PubMed (inception through September 2022) and the results were synthesized qualitatively. Included studies were required to contain content related to peripheral nerve regeneration and some form of neuromodulation. Studies reporting in vivo highlights were subject to a risk of bias assessment using the Cochrane Risk of Bias tool. The results of 52 studies indicate that neuromodulation enhances natural peripheral nerve regeneration processes, but still requires other interventions (e.g., conduits) to control the direction of reinnervation. Additional human studies are warranted to verify the applicability of animal studies and to determine how neuromodulation can be optimized for the greatest functional restoration.

Our objective is to present a brief history of the evolution of peripheral nerve stimulation, the current understanding of peripheral nerve stimulation mechanisms in chronic pain, peripheral nerve stimulation applications in upper extremity chronic pain conditions, and complications of peripheral nerve stimulation. The evolution of peripheral nerve stimulation from the early ages to the current status has been facilitated by discoveries in neurobehavioral mechanisms of pain, advances in technology and percutaneous lead development, and the availability of high-quality portable ultrasound units. Peripheral nerve stimulation application in managing upper extremity pain of amputated limbs, post-stroke shoulder pain, complex regional pain syndrome (CRPS), and median, ulnar, and radial neuropathies are discussed. Finally, we describe complications of peripheral nerve stimulation. The availability of ultrasound-guided peripheral nerve stimulation techniques and superior peripheral nerve stimulation technology have opened up new and minimally invasive treatment options for chronic intractable neuropathic pain of the upper extremity. Additionally, the ability to place peripheral nerve stimulation leads percutaneously without open peripheral nerve surgery expands the pool of implanting physicians, while simultaneously decreasing the risks and complications that are associated with open surgery.

Background/Objectives: Spinal cord injury (SCI) presents significant challenges in restoring motor function, with limited therapeutic options available. Recent advancements in neuromodulation technologies, such as brain-spine interface (BSI), epidural electrical stimulation (EES), and deep brain stimulation (DBS), offer promising solutions. This review article explores the integration of these approaches, focusing on their potential to restore function in SCI patients. Findings: DBS has shown efficacy in SCI treatment with several stimulation sites identified, including the nucleus raphe magnus (NRM) and periaqueductal gray (PAG). However, transitioning from animal to human studies highlights challenges, including the technical risks of targeting the NRM in humans instead of rodent models. Additionally, several other regions have shown potential for motor rehabilitation, including the midbrain locomotor region (MLR) pathways, cuneiform nucleus (CnF), pedunculopontine nucleus (PPN), and lateral hypothalamic. DBS with EES further supports motor recovery in SCI; however, this approach requires high-DBS amplitude, serotonergic pharmacotherapy, and cortical activity decoding to attenuate stress-associated locomotion. BSI combined with EES has recently emerged as a promising novel therapy. Although human studies are limited, animal models have provided evidence supporting its potential. Despite these advancements, the effectiveness of DBS and combined systems remains limited in cases of complete central denervation. Conclusions: The integration and combination of DBS, BSI, and EES represent a transformational approach to treating and restoring function in patients with SCI. While further research is needed to optimize these strategies, these advancements hold immense potential for improving the quality of life in SCI patients and advancing the field of neuromodulation.