Antinocioceptive Effects of Spinal Cord Stimulation by Activation of Periaqueductal Gray Matter and Rostral Ventromedial Medulla: A Mechanism Beyond the Gate Control Theory

Taghipour, Mousa; Ghaffarpasand, Fariborz

doi:10.1111/ner.12788

Cited by 7 publications

(2 citation statements)

References 7 publications

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“…The main analgesic effects of SCS involve activation of the descending pain inhibitory system (54). Taghipour et al suggested that the stimulation of the dorsal column neurons would result in release of neurotransmitters in the dorsal horn by the efferent fibers from periaqueductal gray matter (PAG), rostral ventromedial medulla (RVM) and Raphe nuclei as a mechanism of chronic antinociceptive effects of SCS (55). According to Uno (56), the following mechanisms are likely to involve chronic antinociceptive effects of SCS.…”

Section: Discussionmentioning

confidence: 99%

Three-Year Outcomes After Dorsal Root Ganglion Stimulation in the Treatment of Neuropathic Pain After Peripheral Nerve Injury of Upper and Lower Extremities

Kretzschmar

Reining

Schwarz

2021

Neuromodulation: Technology at the Neural Interface

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Objectives Traumatic peripheral nerve injuries (PNI) often result in severe neuropathic pain which typically becomes chronic, is recalcitrant to common analgesics, and is associated with sleep disturbances, anxiety, and depression. Pharmacological treatments proven to be effective against neuropathic pain are not well tolerated due to side effects. Neuromodulative interventions such as peripheral nerve or spinal cord stimulation have generated mixed results and may be limited by reduced somatotopic specificity. Dorsal root ganglion (DRG) stimulation may be more effective in this etiology. Materials and Methods Twenty‐seven patients were trialed with a DRG neurostimulation system for PNI; trial success (defined as ≥50% pain relief) was 85%, and 23 patients received a permanent stimulator. However, 36‐month outcome data was only available for 21 patients. Pain, quality of life, mental and physical function, and opioid usage were assessed at baseline and at 3‐, 6‐, 12‐, 18‐, 24‐, and 36 months post‐permanent implant. Implant‐related complications were also documented. Results Compared to baseline, we observed a significant pain relief (p < 0.001) at 3 (58%), 12 (66%), 18 (69%), 24 (71%), and 36 months (73%) in 21 patients (52.5 ± 14.2 years; 12 female), respectively. Mental and physical function showed immediate and sustained improvements. Participants reported improvements in quality of life. Opioid dosage reduced significantly (p < 0.001) at 3 (30%), 12 (93%), 18 (98%), 24 (99%), and 36 months (99%), and 20 of 21 patients were completely opioid‐free after 36 months. There were five lead migrations and two electrode fractures (corrected by surgical intervention) and one wound infection (conservatively managed). Conclusions DRG neuromodulation appears to be a safe, effective, and durable option for treating neuropathic pain caused by PNI. The treatment allows cessation of often ineffective pharmacotherapy (including opioid misuse) and significantly improves quality of life.

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Section: Discussionmentioning

confidence: 99%

Three-Year Outcomes After Dorsal Root Ganglion Stimulation in the Treatment of Neuropathic Pain After Peripheral Nerve Injury of Upper and Lower Extremities

Kretzschmar

Reining

Schwarz

2021

Neuromodulation: Technology at the Neural Interface

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“…Sub-and supra-perception SCS modalities are thought to elicit pain relief through distinct mechanisms, but to date there still remains no concrete understanding of how either of these approaches induces analgesia, although several theories have been proposed [35][36][37]. However, one commonality among the various proposed models is that of the importance of dorsal horn targeting.…”

Section: Discussionmentioning

confidence: 99%

Real-World Outcomes Using a Spinal Cord Stimulation Device Capable of Combination Therapy for Chronic Pain: A European, Multicenter Experience

Kallewaard

Paz-Solís

Negri³

et al. 2021

JCM

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Given the differing mechanisms thought to underlie therapeutic sub- and supra-perception-based neurostimulative modalities, Spinal Cord Stimulation (SCS) systems designed for combined delivery of these approaches may help improve analgesic outcomes and quality of life, and reduce treatment failures. This multicenter, observational case-series evaluated 188 patients with chronic back and/or leg pain implanted with an SCS device capable of sequential or simultaneous delivery of sub-perception and supra-perception stimulation programming (i.e., combination therapy) at 16 in Europe. Following implantation, patients were provided with an array of advanced supra-perception programs (e.g., paresthesia-based SCS using multiple independent current sources), and a custom set of sub-perception programs optimized with specific waveforms and/or field shapes. A mean overall pain score of 7.9 ± 1.7 (Standard Deviation (SD)) was reported pre-trial (Baseline). Overall pain was reduced by 4.4 ± 2.8 points (NRS) at 3-months (n = 117) and at 12 months post-implant (n = 90), respectively (p < 0.0001). Substantial quality-of-life (EQ-5D-5L) improvement as assessed at last follow-up was also observed (n = 60). These results suggest that an implanted SCS device capable of combination therapy, while also enabled with patient-specific waveform optimization and stimulation field targeting capabilities, can enable highly effective pain relief and improve quality of life in patients suffering with chronic pain.

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Association Between Spinal Cord Stimulation and Top-Down Nociceptive Inhibition in People With Failed Back Surgery Syndrome: A Cohort Study

Goudman

Brouns²,

Groote

et al. 2019

Physical Therapy

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BackgroundDescending nociceptive inhibitory pathways often malfunction in people with chronic pain. Conditioned pain modulation (CPM) is an experimental evaluation tool for assessing the functioning of these pathways. Spinal cord stimulation (SCS), a well-known treatment option for people with failed back surgery syndrome (FBSS), probably exerts its pain-relieving effect through a complex interplay of segmental and higher-order structures.ObjectiveTo the best of our knowledge, no clinical studies have thoroughly investigated the associations between SCS and CPM.DesignThis was a prospective cohort study in people with FBSS.MethodsSeventeen people who had FBSS and were scheduled for SCS were enrolled in this study. The CPM model was evaluated at both sural nerves and was induced by electrical stimulation as the test stimulus and the cold pressor test as the conditioning stimulus.ResultsBefore SCS, less than 30% of the participants with FBSS showed a CPM effect. Significant increases in the electrical detection threshold on the symptomatic side and the nonsymptomatic side were found. On the symptomatic side, no differences in the numbers of CPM responders before and after SCS could be found. On the nonsymptomatic side, more participants showed a CPM effect during SCS. Additionally, there were significant differences for CPM activation and SCS treatment.LimitationsLimitations were the small sample size and the subjective outcome parameters in the CPM model.ConclusionsThis study revealed a bilateral effect of SCS that suggests the involvement of higher-order structures, such as the periaqueductal gray matter and rostroventromedial medulla (key regions in the descending pathways), as previously suggested by animal research.

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Antinocioceptive Effects of Spinal Cord Stimulation by Activation of Periaqueductal Gray Matter and Rostral Ventromedial Medulla: A Mechanism Beyond the Gate Control Theory

Cited by 7 publications

References 7 publications

Three-Year Outcomes After Dorsal Root Ganglion Stimulation in the Treatment of Neuropathic Pain After Peripheral Nerve Injury of Upper and Lower Extremities

Three-Year Outcomes After Dorsal Root Ganglion Stimulation in the Treatment of Neuropathic Pain After Peripheral Nerve Injury of Upper and Lower Extremities

Real-World Outcomes Using a Spinal Cord Stimulation Device Capable of Combination Therapy for Chronic Pain: A European, Multicenter Experience

Association Between Spinal Cord Stimulation and Top-Down Nociceptive Inhibition in People With Failed Back Surgery Syndrome: A Cohort Study

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