The Impact of Electrical Charge Delivery on Inhibition of Mechanical Hypersensitivity in Nerve-Injured Rats by Sub-Sensory Threshold Spinal Cord Stimulation

Zhiyong Chen, Qian Huang, Fei Yang, Christine Shi, Eellan Sivanesan, Shuguang Liu, Xueming Chen, Sridevi V. Sarma, Louis P. Vera-Portocarrero, Bengt Linderoth, Srinivasa Naga Raja, Yun Guan

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
JournalNeuromodulation
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

Sensory Thresholds
Spinal Cord Stimulation
Hypersensitivity
Pain
Spinal Nerves
Ligation
Inhibition (Psychology)
Paresthesia

Keywords

  • Electrical charge
  • nerve injury
  • pain
  • rat
  • spinal cord stimulation

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Anesthesiology and Pain Medicine

Cite this

The Impact of Electrical Charge Delivery on Inhibition of Mechanical Hypersensitivity in Nerve-Injured Rats by Sub-Sensory Threshold Spinal Cord Stimulation. / Chen, Zhiyong; Huang, Qian; Yang, Fei; Shi, Christine; Sivanesan, Eellan; Liu, Shuguang; Chen, Xueming; Sarma, Sridevi V.; Vera-Portocarrero, Louis P.; Linderoth, Bengt; Raja, Srinivasa Naga; Guan, Yun.

In: Neuromodulation, 01.01.2018.

Research output: Contribution to journalArticle

Chen, Zhiyong ; Huang, Qian ; Yang, Fei ; Shi, Christine ; Sivanesan, Eellan ; Liu, Shuguang ; Chen, Xueming ; Sarma, Sridevi V. ; Vera-Portocarrero, Louis P. ; Linderoth, Bengt ; Raja, Srinivasa Naga ; Guan, Yun. / The Impact of Electrical Charge Delivery on Inhibition of Mechanical Hypersensitivity in Nerve-Injured Rats by Sub-Sensory Threshold Spinal Cord Stimulation. In: Neuromodulation. 2018.
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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.",
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AU - Chen, Zhiyong

AU - Huang, Qian

AU - Yang, Fei

AU - Shi, Christine

AU - Sivanesan, Eellan

AU - Liu, Shuguang

AU - Chen, Xueming

AU - Sarma, Sridevi V.

AU - Vera-Portocarrero, Louis P.

AU - Linderoth, Bengt

AU - Raja, Srinivasa Naga

AU - Guan, Yun

PY - 2018/1/1

Y1 - 2018/1/1

N2 - 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.

AB - 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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KW - pain

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