Spinal Cord Stimulation Attenuates Below-Level Mechanical Hypersensitivity in Rats After Thoracic Spinal Cord Injury

Duan, Wanru; Huang, Qian; Yang, Fei; He, Shao Qiu; Guan, Yun

doi:10.1111/ner.13248

Cited by 10 publications

(9 citation statements)

References 52 publications

(129 reference statements)

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“…Motor targeted ISMS was delivered as a series of discrete, cathode-leading pulses at 7 Hz, 200 μs/phase, 0 s inter-phase interval, and 90% of resting motor threshold (typically ~3-12 μA/phase). These ISMS parameters are consistent both with values that induced functionally meaningful enhancements of spinal motor output below a chronic SCI (25) and with stimulation intensities (e.g., 80-90% of resting motor threshold) commonly used in studies of ESS parametrized to treat pain (46,47).…”

Section: Methodssupporting

confidence: 82%

Motor-targeted spinal stimulation promotes concurrent rebalancing of pathologic nociceptive transmission in chronic spinal cord injury

Bandres

Gomes²,

McPherson

2023

Preprint

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Electrical stimulation of spinal networks below a spinal cord injury (SCI) is a promising approach to restore functions compromised by inadequate excitatory neural drive. The most translationally successful examples are paradigms intended to increase neural transmission in weakened yet spared motor pathways and spinal motor networks rendered dormant after being severed from their inputs by lesion. Less well understood is whether spinal stimulation is also capable of reducing neural transmission in pathways made pathologically overactive by SCI. Debilitating spasms, spasticity, and neuropathic pain are all common manifestations of hyperexcitable spinal responses to sensory feedback. But whereas spasms and spasticity can often be managed pharmacologically, SCI-related neuropathic pain is notoriously medically refractory. Interestingly, however, spinal stimulation is a clinically available option for ameliorating neuropathic pain arising from etiologies other than SCI, and it has traditionally been assumed to modulate sensorimotor networks overlapping with those engaged by spinal stimulation for motor rehabilitation. Thus, we reasoned that spinal stimulation intended to increase transmission in motor pathways may simultaneously reduce transmission in spinal pain pathways. Using a well-validated pre-clinical model of SCI that results in severe bilateral motor impairments and SCI-related neuropathic pain, we show that the responsiveness of neurons integral to the development and persistence of the neuropathic pain state can be enduringly reduced by motor-targeted spinal stimulation while preserving spinal responses to non-painrelated sensory feedback. These results suggest that spinal stimulation paradigms could be intentionally designed to afford multi-modal therapeutic benefits, directly addressing the diverse, intersectional rehabilitation goals of people living with SCI.

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Section: Methodssupporting

confidence: 82%

Motor-targeted spinal stimulation promotes concurrent rebalancing of pathologic nociceptive transmission in chronic spinal cord injury

Bandres

Gomes²,

McPherson

2023

Preprint

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“…Electrical stimulation of spinal circuits is also an emerging approach to manage enigmatic chronic pain syndromes such as persistent spinal pain syndrome, complex regional pain syndrome, neuropathic pain syndromes, and ischemic pain syndromes [9][10][11][12]. The ability of spinal stimulation to reduce pathologic neural transmission associated with SCI-NP has only been preliminarily investigated [13]. However, many of the therapeutic benefits of spinal stimulation for SCI-related motor impairments derive from a neural mechanism that is also presumed to underlie many of the benefits of paresthesia-based spinal stimulation for neuropathic pain.…”

Section: Introductionmentioning

confidence: 99%

Spinal stimulation for motor rehabilitation immediately modulates nociceptive transmission

Bandres¹,

Gomes²,

McPherson³

2022

J. Neural Eng.

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Objective: Spinal cord injury (SCI) often results in debilitating movement impairments and neuropathic pain. Electrical stimulation of spinal neurons holds considerable promise both for enhancing neural transmission in weakened motor pathways and for reducing neural transmission in overactive nociceptive pathways. However, spinal stimulation paradigms currently under development for individuals living with SCI continue overwhelmingly to be developed in the context of motor rehabilitation alone. The objective of this study is to test the hypothesis that motor-targeted spinal stimulation simultaneously modulates spinal nociceptive transmission. Approach: We characterized the neuromodulatory actions of motor-targeted intraspinal microstimulation (ISMS) on the firing dynamics of large populations of discrete nociceptive specific and wide dynamic range neurons. Neurons were accessed via dense microelectrode arrays implanted in vivo into lumbar enlargement of rats. Nociceptive and non-nociceptive cutaneous transmission was induced before, during, and after ISMS by mechanically probing the L5 dermatome. Main results: Our primary findings are that (1) sub-motor threshold ISMS delivered to spinal motor pools immediately modulates concurrent nociceptive transmission; (2) the magnitude of anti-nociceptive effects increases with longer durations of ISMS, including robust carryover effects; (3) the majority of all identified nociceptive-specific and wide dynamic range neurons exhibit firing rate reductions after only 10 min of ISMS; and (4) ISMS does not increase spinal responsiveness to non-nociceptive cutaneous transmission. These results lead to the conclusion that ISMS parameterized to enhance motor output results in an overall net decrease in spinal nociceptive transmission. Significance: These results suggest that ISMS may hold translational potential for neuropathic pain-related applications and that it may be uniquely suited to delivering multi-modal therapeutic benefits for individuals living with SCI.

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“…The supraspinal mechanisms are the result of activation of supraspinal areas and modulation of incoming nociceptive signaling at the spinal levels through their descending projections. In SCI pain, it is possible that supraspinal mechanisms, hyperexcitability of wide dynamic range neurons near and proximal to the lesion, and sensitization of nociceptive‐specific and low‐threshold dorsal horn neurons may play an important role 19 . Activation of thermosensory nociceptive neurons in clinically complete SCI patients mimics chronic pain sensations implying that activity in residual spinothalamic pathways plays a crucial role in maintaining central pain 20 .…”

Section: Discussionmentioning

confidence: 99%

“…In SCI pain, it is possible that supraspinal mechanisms, hyperexcitability of wide dynamic range neurons near and proximal to the lesion, and sensitization of nociceptive‐specific and low‐threshold dorsal horn neurons may play an important role. 19 Activation of thermosensory nociceptive neurons in clinically complete SCI patients mimics chronic pain sensations implying that activity in residual spinothalamic pathways plays a crucial role in maintaining central pain. 20 In addition, the SCI can interrupt descending inhibitory pathways arising from the brainstem which play an important role in modulation of dorsal horn neurons.…”

Section: Discussionmentioning

confidence: 99%

Spinal cord stimulation in patients suffering from chronic pain after surgery for spinal intradural tumors: A case report and literature summary

2022

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Background:The prevalence of pain after treatment of a spinal intradural tumor is remarkably high, approximately up to 40% of the patients suffer from central neuropathic pain. Publications on spinal cord stimulation (SCS) and its effect on pain caused by intradural spinal tumors are rare. We discuss the case of a patient suffering from chronic pain after removal of a Th7 level meningioma who was successfully treated with SCS and give an overview of the literature.Methods: MEDLINE database was searched for neuropathic pain and intradural tumors. Results:The initial search identified 35 articles, including hand-searched manuscripts. Six articles were included for analysis.Case Report: A 57-year-old female suffers from neuropathic pain in both legs after surgical removal of a Th7 level intradural meningioma. Postoperative magnetic resonance imaging shows no gross abnormalities, although she developed chronic pain in both legs. Pain in combination with side effects of analgesic intake are too disabling to have decent quality of life. A successful implantation of SCS is achieved at Th5 level as a treatment for the central neuropathic pain, and, at 36 months follow-up, there is significant pain relief and almost complete discontinuation of analgesics.Discussion: Central pain from spinal intradural tumors may have a different mechanism of origin than pain seen after an acute spinal cord injury (SCI).However, the basic principles of neuromodulation are the same in both etiologies, as for successful stimulation intact pathways in the spinal cord are necessary. The efficacy of SCS as treatment in intradural spinal tumors is rarely described as only a handful of case reports are published. Interestingly, the case reports show that stimulation both above and below the lesion can be effective. In patients with incomplete SCI or intradural tumor resection stimulation below the lesion could be considered and tried in a trial setting before definitive implantation.

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Spinal Cord Stimulation Attenuates Below-Level Mechanical Hypersensitivity in Rats After Thoracic Spinal Cord Injury

Cited by 10 publications

References 52 publications

Motor-targeted spinal stimulation promotes concurrent rebalancing of pathologic nociceptive transmission in chronic spinal cord injury

Motor-targeted spinal stimulation promotes concurrent rebalancing of pathologic nociceptive transmission in chronic spinal cord injury

Spinal stimulation for motor rehabilitation immediately modulates nociceptive transmission

Spinal cord stimulation in patients suffering from chronic pain after surgery for spinal intradural tumors: A case report and literature summary

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