Zhiyong Chen1, Qian Huang1, Fei Yang1,2, Christine Shi1, Eellan Sivanesan1, Shuguang Liu1,3, Xueming Chen4, Sridevi V Sarma5, Louis P Vera-Portocarrero6, Bengt Linderoth7, Srinivasa N Raja1, Yun Guan1,8. 1. Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, School of Medicine, Baltimore, MD, USA. 2. Department of Neurobiology, Capital Medical University, Beijing, China. 3. Department of Orthopedics, Hong Hui Hospital, Affiliated Hospital of Medical School, Xi'an Jiaotong University, Xi'an, Shanxi, China. 4. Department of Orthopedics, Luhe Hospital, Capital Medical University, Beijing, China. 5. Department of Biomedical Engineering, Institute for Computational Medicine, Johns Hopkins University, Baltimore, MD, USA. 6. Core Technology & Research, Medtronic Inc., Minneapolis, MN, USA. 7. Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden. 8. Department of Neurological Surgery, Johns Hopkins University, School of Medicine, Baltimore, MD, USA.
Abstract
OBJECTIVES: Spinal cord stimulation (SCS) represents an important neurostimulation therapy for pain. A new ultra-high frequency (10,000 Hz) SCS paradigm has shown improved pain relief without eliciting paresthesia. We aim to determine whether sub-sensory threshold SCS of lower frequencies also can inhibit mechanical hypersensitivity in nerve-injured rats and examine how electric charge delivery of stimulation may affect pain inhibition by different patterns of subthreshold SCS. MATERIALS AND METHODS: We used a custom-made quadripolar electrode (Medtronic Inc., Minneapolis, MN, USA) to provide bipolar SCS epidurally at the T10 to T12 vertebral level. According to previous findings, SCS was tested at 40% of the motor threshold, which is considered to be a sub-sensory threshold intensity in rats. Paw withdrawal thresholds to punctate mechanical stimulation were measured before and after SCS in rats that received an L5 spinal nerve ligation. RESULTS: Both 10,000 Hz (10 kHz, 0.024 msec) and lower frequencies (200 Hz, 1 msec; 500 Hz, 0.5 msec; 1200 Hz; 0.2 msec) of subthreshold SCS (120 min) attenuated mechanical hypersensitivity, as indicated by increased paw withdrawal thresholds after stimulation in spinal nerve ligation rats. Pain inhibition from different patterns of subthreshold SCS was not governed by individual stimulation parameters. However, correlation analysis suggests that pain inhibition from 10 kHz subthreshold SCS in individual animals was positively correlated with the electric charges delivered per second (electrical dose). CONCLUSIONS: Inhibition of neuropathic mechanical hypersensitivity can be achieved with low-frequency subthreshold SCS by optimizing the electric charge delivery, which may affect the effect of SCS in individual animals.
OBJECTIVES: Spinal cord stimulation (SCS) represents an important neurostimulation therapy for pain. A new ultra-high frequency (10,000 Hz) SCS paradigm has shown improved pain relief without eliciting paresthesia. We aim to determine whether sub-sensory threshold SCS of lower frequencies also can inhibit mechanical hypersensitivity in nerve-injured rats and examine how electric charge delivery of stimulation may affect pain inhibition by different patterns of subthreshold SCS. MATERIALS AND METHODS: We used a custom-made quadripolar electrode (Medtronic Inc., Minneapolis, MN, USA) to provide bipolar SCS epidurally at the T10 to T12 vertebral level. According to previous findings, SCS was tested at 40% of the motor threshold, which is considered to be a sub-sensory threshold intensity in rats. Paw withdrawal thresholds to punctate mechanical stimulation were measured before and after SCS in rats that received an L5 spinal nerve ligation. RESULTS: Both 10,000 Hz (10 kHz, 0.024 msec) and lower frequencies (200 Hz, 1 msec; 500 Hz, 0.5 msec; 1200 Hz; 0.2 msec) of subthreshold SCS (120 min) attenuated mechanical hypersensitivity, as indicated by increased paw withdrawal thresholds after stimulation in spinal nerve ligation rats. Pain inhibition from different patterns of subthreshold SCS was not governed by individual stimulation parameters. However, correlation analysis suggests that pain inhibition from 10 kHz subthreshold SCS in individual animals was positively correlated with the electric charges delivered per second (electrical dose). CONCLUSIONS: Inhibition of neuropathic mechanical hypersensitivity can be achieved with low-frequency subthreshold SCS by optimizing the electric charge delivery, which may affect the effect of SCS in individual animals.
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