ArticleMolecular pain2015
Spinal cord stimulation modulates supraspinal centers of the descending antinociceptive system in rats with unilateral spinal nerve injury.
Article in Molecular pain, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 2 of them syntheses that pooled it.
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Who cites it
19 citing papers in PubMed, 2 syntheses or guidelines pooled it, 45 citations in OpenAlex.
- Spinal Cord Stimulation for Painful Diabetic Neuropathy: A Systematic Review and Meta-Analysis of High- and Low-Frequency Modalities.Pain research & management · 2026Pooled it
- Pooled it
- Dual-frequency spinal cord stimulation increases responder rates for treatment of neuropathic pain.Pain · 2026Article
- Review
- Characterization of preclinical models to investigate spinal cord stimulation for neuropathic pain: a systematic review and meta-analysis.Pain reports · 2025Review
- Neurochemical crossroads: exploring the neurotransmitter network in chronic pain and depression comorbidity.Frontiers in molecular neuroscience · 2025Review
- Alteration of BDNF and noradrenergic markers in locus coeruleus in a mouse model of cancer-induced bone pain.PloS one · 2025Article
- Recent Trends in Physical Therapy Interventions and Neuromodulation Techniques to Improve Neurorehabilitation.CNS & neurological disorders drug targets · 2025Review
- Spinal cord vascular degeneration impairs duloxetine penetration.Frontiers in pain research (Lausanne, Switzerland) · 2023Article
- Narrative review of current neuromodulation modalities for spinal cord injury.Frontiers in pain research (Lausanne, Switzerland) · 2023Review
- Spinal Cord Stimulation to Treat Unresponsive Cancer Pain: A Possible Solution in Palliative Oncological Therapy.Life (Basel, Switzerland) · 2022Review
- Involvement of Opioid Peptides in the Analgesic Effect of Spinal Cord Stimulation in a Rat Model of Neuropathic Pain.Neuroscience bulletin · 2022Article
- Exploration of the Supraspinal Hypotheses about Spinal Cord Stimulation and Dorsal Root Ganglion Stimulation: A Systematic Review.Journal of clinical medicine · 2021Review
- Monoaminergic and Opioidergic Modulation of Brainstem Circuits: New Insights Into the Clinical Challenges of Pain Treatment?Frontiers in pain research (Lausanne, Switzerland) · 2021Review
- Spinal cord stimulation in chronic pain: evidence and theory for mechanisms of action.Bioelectronic medicine · 2019Article
- Supraspinal Mechanisms of Spinal Cord Stimulation for Modulation of Pain: Five Decades of Research and Prospects for the Future.Anesthesiology · 2019Review
- Motor cortex and pain control: exploring the descending relay analgesic pathways and spinal nociceptive neurons in healthy conscious rats.Behavioral and brain functions : BBF · 2019Article
- Monoamines as Drug Targets in Chronic Pain: Focusing on Neuropathic Pain.Frontiers in neuroscience · 2019Review
- Long-Term Spinal Cord Stimulation Alleviates Mechanical Hypersensitivity and Increases Peripheral Cutaneous Blood Perfusion in Experimental Painful Diabetic Polyneuropathy.Neuromodulation : journal of the International Neuromodulation Society · 2018Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe descending antinociceptive system (DAS) is thought to play crucial roles in the antinociceptive effect of spinal cord stimulation (SCS), especially through its serotonergic pathway. The nucleus raphe magnus (NRM) in the rostral ventromedial medulla is a major source of serotonin [5-hydroxytryptamine (5-HT)] to the DAS, but the role of the dorsal raphe nucleus (DRN) in the ventral periaqueductal gray matter is still unclear. Moreover, the influence of the noradrenergic pathway is largely unknown. In this study, we evaluated the involvement of these serotonergic and noradrenergic pathways in SCS-induced antinociception by behavioral analysis of spinal nerve-ligated (SNL) rats. We also investigated immunohistochemical changes in the DRN and locus coeruleus (LC), regarded as the adrenergic center of the DAS, and expression changes of synthetic enzymes of 5-HT [tryptophan hydroxylase (TPH)] and norepinephrine [dopamine β-hydroxylase (DβH)] in the spinal dorsal horn.
resultsIntrathecally administered methysergide, a 5-HT1- and 5-HT2-receptor antagonist, and idazoxan, an α2-adrenergic receptor antagonist, equally abolished the antinociceptive effect of SCS. The numbers of TPH-positive serotonergic and phosphorylated cyclic AMP response element binding protein (pCREB)-positive neurons and percentage of pCREB-positive serotonergic neurons in the DRN significantly increased after 3-h SCS. Further, the ipsilateral-to-contralateral immunoreactivity ratio of DβH increased in the LC of SNL rats and reached the level seen in naïve rats, even though the number of pCREB-positive neurons in the LC was unchanged by SNL and SCS. Moreover, 3-h SCS did not increase the expression levels of TPH and DβH in the spinal dorsal horn.
conclusionsThe serotonergic and noradrenergic pathways of the DAS are involved in the antinociceptive effect of SCS, but activation of the DRN might primarily be responsible for this effect, and the LC may have a smaller contribution. SCS does not potentiate the synthetic enzymes of 5HT and norepinephrine in the neuropathic spinal cord.
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