ArticleFrontiers in physiology2012
Nociceptors as chronic drivers of pain and hyperreflexia after spinal cord injury: an adaptive-maladaptive hyperfunctional state hypothesis.
Article in Frontiers in physiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 1 of them a synthesis that pooled it.
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Who cites it
49 citing papers in PubMed, 1 synthesis or guideline pooled it, 95 citations in OpenAlex.
- Effects of Virtual Walking on Neuropathic Pain in People With Spinal Cord Injury: A Systematic Review.Topics in spinal cord injury rehabilitation · 2025Pooled it
- The Increased Activity of CaV3.2 Channels Contributes to Nociceptors' Hyperexcitability and Chronic Neuropathic Pain Following Spinal Cord Injury in Mice.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- Article
- Structural insights into the function, dysfunction and modulation of Kv3 channels.Neuropharmacology · 2025Review
- Review
- Article
- Chemogenetic Attenuation of Acute Nociceptive Signaling Enhances Functional Outcomes Following Spinal Cord Injury.Journal of neurotrauma · 2024Article
- Widespread latent hyperactivity of nociceptors outlasts enhanced avoidance behavior following incision injury.bioRxiv : the preprint server for biology · 2024Article
- Relating Spinal Injury-Induced Neuropathic Pain and Spontaneous Afferent Activity to Sleep and Respiratory Dysfunction.Journal of neurotrauma · 2023Article
- Post-injury pain and behaviour: a control theory perspective.Nature reviews. Neuroscience · 2023Review
- Persistent nociceptor hyperactivity as a painful evolutionary adaptation.Trends in neurosciences · 2023Review
- Exaptation and Evolutionary Adaptation in Nociceptor Mechanisms Driving Persistent Pain.Brain, behavior and evolution · 2023Review
- Enhanced nociceptive behavior and expansion of associated primary afferents in a rabbit model of cerebral palsy.Journal of neuroscience research · 2022Article
- Dorsal horn neuronal sparing predicts the development of at-level mechanical allodynia following cervical spinal cord injury in mice.Experimental neurology · 2022Article
- Broad opioid antagonism amplifies disruption of locomotor function following therapy-like hindlimb stretching in spinal cord injured rats.Spinal cord · 2022Article
- Targeting Vascular endothelial growth factor A with soluble vascular endothelial growth factor receptor 1 ameliorates nerve injury-induced neuropathic pain.Molecular pain · 2022Article
- Contribution of T-Type Calcium Channels to Spinal Cord Injury-Induced Hyperexcitability of Nociceptors.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020Article
- Regional Hyperexcitability and Chronic Neuropathic Pain Following Spinal Cord Injury.Cellular and molecular neurobiology · 2020Review
- Adaptive mechanisms driving maladaptive pain: how chronic ongoing activity in primary nociceptors can enhance evolutionary fitness after severe injury.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2019Article
- Transcriptome of dorsal root ganglia caudal to a spinal cord injury with modulated behavioral activity.Scientific data · 2019Article
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1 author at 1 institution in 1 country.
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Abstract
Spinal cord injury (SCI) causes chronic peripheral sensitization of nociceptors and persistent generation of spontaneous action potentials (SA) in peripheral branches and the somata of hyperexcitable nociceptors within dorsal root ganglia (DRG). Here it is proposed that SCI triggers in numerous nociceptors a persistent hyperfunctional state (peripheral, synaptic, and somal) that originally evolved as an adaptive response to compensate for loss of sensory terminals after severe but survivable peripheral injury. In this hypothesis, nociceptor somata monitor the status of their own receptive field and the rest of the body by integrating signals received by their peripheral and central branches and the soma itself. A nociceptor switches into a potentially permanent hyperfunctional state when central neural, glial, and inflammatory signal combinations are detected that indicate extensive peripheral injury. Similar signal combinations are produced by SCI and disseminated widely to uninjured as well as injured nociceptors. This paper focuses on the uninjured nociceptors that are altered by SCI. Enhanced activity generated in below-level nociceptors promotes below-level central sensitization, somatic and autonomic hyperreflexia, and visceral dysfunction. If sufficient ascending fibers survive, enhanced activity in below-level nociceptors contributes to below-level pain. Nociceptor activity generated above the injury level contributes to at- and above-level sensitization and pain (evoked and spontaneous). Thus, SCI triggers a potent nociceptor state that may have been adaptive (from an evolutionary perspective) after severe peripheral injury but is maladaptive after SCI. Evidence that hyperfunctional nociceptors make large contributions to behavioral hypersensitivity after SCI suggests that nociceptor-specific ion channels required for nociceptor SA and hypersensitivity offer promising targets for treating chronic pain and hyperreflexia after SCI.
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