Objective Measures to Characterize the Physiological Effects of Spinal Cord Stimulation in Neuropathic Pain: A Literature Review

Sankarasubramanian, Vishwanath; Harte, Steven E.; Chiravuri, Srinivas; Harris, Richard E.; Brummett, Chad M.; Patil, Parag G.; Clauw, Daniel J.; Lempka, Scott F.

doi:10.1111/ner.12804

Cited by 29 publications

(28 citation statements)

References 129 publications

(409 reference statements)

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“…Fourteen days post-lesion is considered chronic neuropathic pain in most pre-clinical studies where chronic neuropathic pain has been defined as that which persisted 14 days post-lesion; 30-40 min SCS stimulation paradigms have been tested in these studies [50][51][52]. On day 3 after peripheral nerve injury, the central sensitization process is not as robust as it is after 14 days.…”

Section: Discussionmentioning

confidence: 99%

Suppression of Superficial Microglial Activation by Spinal Cord Stimulation Attenuates Neuropathic Pain Following Sciatic Nerve Injury in Rats

Shinoda

Fujita

Sugawara

et al. 2020

IJMS

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We evaluated the mechanisms underlying the spinal cord stimulation (SCS)-induced analgesic effect on neuropathic pain following spared nerve injury (SNI). On day 3 after SNI, SCS was performed for 6 h by using electrodes paraspinally placed on the L4-S1 spinal cord. The effects of SCS and intraperitoneal minocycline administration on plantar mechanical sensitivity, microglial activation, and neuronal excitability in the L4 dorsal horn were assessed on day 3 after SNI. The somatosensory cortical responses to electrical stimulation of the hind paw on day 3 following SNI were examined by using in vivo optical imaging with a voltage-sensitive dye. On day 3 after SNI, plantar mechanical hypersensitivity and enhanced microglial activation were suppressed by minocycline or SCS, and L4 dorsal horn nociceptive neuronal hyperexcitability was suppressed by SCS. In vivo optical imaging also revealed that electrical stimulation of the hind paw-activated areas in the somatosensory cortex was decreased by SCS. The present findings suggest that SCS could suppress plantar SNI-induced neuropathic pain via inhibition of microglial activation in the L4 dorsal horn, which is involved in spinal neuronal hyperexcitability. SCS is likely to be a potential alternative and complementary medicine therapy to alleviate neuropathic pain following nerve injury.

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Section: Discussionmentioning

confidence: 99%

Suppression of Superficial Microglial Activation by Spinal Cord Stimulation Attenuates Neuropathic Pain Following Sciatic Nerve Injury in Rats

Shinoda

Fujita

Sugawara

et al. 2020

IJMS

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“…An inhibitory effect of traditional SCS on somatosensory evoked potentials, and potential key regions like the thalamus and the anterior cingulate cortex, could play a role in the mechanism of action of SCS as well [1–4]. Several studies provided evidence of the impact of SCS on the descending nociceptive inhibitory system (DNIS) resulting in this inhibitory supraspinal effect [5, 6]. The DNIS comprises a network of cortical and subcortical brain (bilateral anterior insulae, the anterior cingulate cortex, bilateral middle frontal gyri, both amygdalae) and brainstem (rostral ventromedial medulla and the periaqueductal gray) regions that can inhibit nociceptive afferent brain input [7–9] [10, 11].…”

Section: Introductionmentioning

confidence: 99%

Effects of spinal cord stimulation on heart rate variability in patients with Failed Back Surgery Syndrome

et al. 2019

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Background Building on the recent finding that chronic pain patients with impaired functioning of the descending nociceptive inhibitory system (DNIS) present lower resting heart rate variability (HRV), this study aims to investigate the impact of Spinal Cord Stimulation (SCS) on HRV in patients with Failed Back Surgery Syndrome (FBSS). More precisely, we hypothesize that SCS influences the DNIS, with increased parasympathetic tone as a consequence, as measurable by HRV analysis. Methods Twenty-two patients diagnosed with FBSS and treated with SCS participated in this study. HRV was measured with a 2-lead ECG registration tool during on and off states of SCS. HRV analysis for time, frequency, time-frequency and nonlinear domain parameters was based on a 5-minute recording segment. Results The mean heart rate and low frequency power were significantly lower when SCS was activated. HRV, absolute and normalized high frequency power significantly increased during SCS compared to without SCS. The ratio of low frequency/high frequency ratios, as parameter for global sympathetic-parasympathetic equilibrium, significantly decreased when SCS was activated. Conclusions When SCS is switched off, patients with FBSS present relatively stronger sympathetic tone and weaker parasympathetic activity. Activation of the SCS, possibly via stimulation of the DNIS, restores this disbalance of autonomic activity.

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“…The neurophysiological effects of P-SCS on the human spinal cord has been a crucial area of study in understanding the mechanistic properties of the therapy, as well as furthering its development (Sankarasubramanian et al, 2018a). The effect of P-SCS in cortical processing can be measured via somatosensory evoked potentials (SSEPs), or the activity in the cortex measured via EEG that results from peripheral electrical stimulation (Fig.…”

Section: Neurophysiologic Testingmentioning

confidence: 99%

“…Using this paradigm, numerous studies have demonstrated that P-SCS can have an inhibitory effect on the amplitude of the SSEP in response to noxious stimuli, which in turn would modify the experience of the painful sensation (Wolter et al, 2013). Additional research has looked into the effect of P-SCS on the sensorimotor reflexes mediated by Aβ, Aδ, and C sensory afferents (Sankarasubramanian et al, 2018a; De Andrade et al, 2010). In a study of 20 patients, the authors demonstrated that P-SCS attenuated the H-reflex, a monosynaptic arc in the spinal cord, such as the Achilles tendon reflex, as well as the RIII, a polysynaptic withdrawal reflex, such as withdrawing one’s hand from a hot surface.…”

Section: Neurophysiologic Testingmentioning

confidence: 99%

Spinal cord stimulation in chronic pain: evidence and theory for mechanisms of action

et al. 2019

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Well-established in the field of bioelectronic medicine, Spinal Cord Stimulation (SCS) offers an implantable, nonpharmacologic treatment for patients with intractable chronic pain conditions. Chronic pain is a widely heterogenous syndrome with regard to both pathophysiology and the resultant phenotype. Despite advances in our understanding of SCS-mediated antinociception, there still exists limited evidence clarifying the pathways recruited when patterned electric pulses are applied to the epidural space. The rapid clinical implementation of novel SCS methods including burst, high frequency and dorsal root ganglion SCS has provided the clinician with multiple options to treat refractory chronic pain. While compelling evidence for safety and efficacy exists in support of these novel paradigms, our understanding of their mechanisms of action (MOA) dramatically lags behind clinical data. In this review, we reconstruct the available basic science and clinical literature that offers support for mechanisms of both paresthesia spinal cord stimulation (P-SCS) and paresthesia-free spinal cord stimulation (PF-SCS). While P-SCS has been heavily examined since its inception, PF-SCS paradigms have recently been clinically approved with the support of limited preclinical research. Thus, wide knowledge gaps exist between their clinical efficacy and MOA. To close this gap, many rich investigative avenues for both P-SCS and PF-SCS are underway, which will further open the door for paradigm optimization, adjunctive therapies and new indications for SCS. As our understanding of these mechanisms evolves, clinicians will be empowered with the possibility of improving patient care using SCS to selectively target specific pathophysiological processes in chronic pain.

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Objective Measures to Characterize the Physiological Effects of Spinal Cord Stimulation in Neuropathic Pain: A Literature Review

Cited by 29 publications

References 129 publications

Suppression of Superficial Microglial Activation by Spinal Cord Stimulation Attenuates Neuropathic Pain Following Sciatic Nerve Injury in Rats

Suppression of Superficial Microglial Activation by Spinal Cord Stimulation Attenuates Neuropathic Pain Following Sciatic Nerve Injury in Rats

Effects of spinal cord stimulation on heart rate variability in patients with Failed Back Surgery Syndrome

Spinal cord stimulation in chronic pain: evidence and theory for mechanisms of action

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