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Time-dynamic pulse modulation of spinal cord stimulation reduces mechanical hypersensitivity and spontaneous pain in rats.

ABSTRACT: Enhancing the efficacy of spinal cord stimulation (SCS) is needed to alleviate the burden of chronic pain and dependence on opioids. Present SCS therapies are characterized by the delivery of constant stimulation in the form of trains of tonic pulses (TPs). We tested the hypothesis that modulated SCS using novel time-dynamic pulses (TDPs) leads to improved analgesia and compared the effects of SCS using conventional TPs and a collection of TDPs in a rat model of neuropathic pain according to a longitudinal, double-blind, and crossover design. We tested the effects of the following SCS patterns on paw withdrawal threshold and resting state EEG theta power as a biomarker of spontaneous pain: Tonic (conventional), amplitude modulation, pulse width modulation, sinusoidal rate modulation, and stochastic rate modulation. Results demonstrated that under the parameter settings tested in this study, all tested patterns except pulse width modulation, significantly reversed mechanical hypersensitivity, with stochastic rate modulation achieving the highest efficacy, followed by the sinusoidal rate modulation. The anti-nociceptive effects of sinusoidal rate modulation on EEG outlasted SCS duration on the behavioral and EEG levels. These results suggest that TDP modulation may improve clinical outcomes by reducing pain intensity and possibly improving the sensory experience.

SUBMITTER: Edhi MM

PROVIDER: S-EPMC7683561 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Time-dynamic pulse modulation of spinal cord stimulation reduces mechanical hypersensitivity and spontaneous pain in rats.

Edhi Muhammad M MM Heijmans Lonne L Vanent Kevin N KN Bloye Kiernan K Baanante Amanda A Jeong Ki-Soo KS Leung Jason J Zhu Changfang C Esteller Rosana R Saab Carl Y CY

Scientific reports 20201123 1

Enhancing the efficacy of spinal cord stimulation (SCS) is needed to alleviate the burden of chronic pain and dependence on opioids. Present SCS therapies are characterized by the delivery of constant stimulation in the form of trains of tonic pulses (TPs). We tested the hypothesis that modulated SCS using novel time-dynamic pulses (TDPs) leads to improved analgesia and compared the effects of SCS using conventional TPs and a collection of TDPs in a rat model of neuropathic pain according to a l ...[more]

PMID: 33230202

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Project description:Angina pectoris is cardiac pain that is a common clinical symptom often resulting from myocardial ischemia. Spinal cord stimulation (SCS) is effective in treating refractory angina pectoris, but its underlying mechanisms have not been fully elucidated. The spinal dorsal horn is the first region of the central nervous system that receives nociceptive information; it is also the target of SCS. In the spinal cord, glial (astrocytes and microglia) activation is involved in the initiation and persistence of chronic pain. Thus, the present study investigated the possible cardiac pain‑relieving effects of SCS on spinal dorsal horn glia in chronic myocardial ischemia (CMI). CMI was established by left anterior descending artery ligation surgery, which induced significant spontaneous/ongoing cardiac pain behaviors, as measured using the open field test in rats. SCS effectively improved such behaviors as shown by open field and conditioned place preference tests in CMI model rats. SCS suppressed CMI‑induced spinal dorsal horn microglial activation, with downregulation of ionized calcium‑binding adaptor protein‑1 expression. Moreover, SCS inhibited CMI‑induced spinal expression of phosphorylated‑p38 MAPK, which was specifically colocalized with the spinal dorsal horn microglia rather than astrocytes and neurons. Furthermore, SCS could depress spinal neuroinflammation by suppressing CMI‑induced IL‑1β and TNF‑α release. Intrathecal administration of minocycline, a microglial inhibitor, alleviated the cardiac pain behaviors in CMI model rats. In addition, the injection of fractalkine (microglia‑activating factor) partially reversed the SCS‑produced analgesic effects on CMI‑induced cardiac pain. These results indicated that the therapeutic mechanism of SCS on CMI may occur partially through the inhibition of spinal microglial p38 MAPK pathway activation. The present study identified a novel mechanism underlying the SCS‑produced analgesic effects on chronic cardiac pain.

Dataset Information

Time-dynamic pulse modulation of spinal cord stimulation reduces mechanical hypersensitivity and spontaneous pain in rats.

Publications

Time-dynamic pulse modulation of spinal cord stimulation reduces mechanical hypersensitivity and spontaneous pain in rats.

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