ArticlePain2005
Neuropathic pain: early spontaneous afferent activity is the trigger.
Article in Pain, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 102 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
102 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Clinical significance of tumor necrosis factor-α inhibitors in the treatment of sciatica: a systematic review and meta-analysis.PloS one · 2014Pooled it
- Glial cells in neuropathic pain.Physiological reviews · 2026Review
- Human birth tissue products for pathological pain: mechanisms, evidence, and translational outlook.Journal of translational medicine · 2026Review
- CLARIX FLO Inhibits DRG Adhesion-Induced Neuropathic Pain Through the CD44-TRPV1 Signaling Pathway.International journal of molecular sciences · 2026Article
- Quantum Mechanical Mechanisms in the Therapeutic Effects of Spinal Cord Stimulation to Treat Chronic Neuropathic Pain: A Quantum Computational Model.Journal of pain research · 2026Article
- Article
- Tetrodotoxin Delivery Pen Safely Uses Potent Natural Neurotoxin to Manage Severe Cutaneous Pain.Advanced healthcare materials · 2025Article
- Low intensity trans-spinal focused ultrasound reduces mechanical sensitivity and suppresses spinal microglia activation in rats with chronic constriction injury.Bioelectronic medicine · 2025Article
- Mechanisms for reducing/eliminating chronic neuropathic pain with a focus on platelet-rich plasma.Experimental biology and medicine (Maywood, N.J.) · 2025Review
- Clinically Reducing/Eliminating Chronic Neuropathic Pain by Bridging Peripheral Nerve Gaps with an Autograft within a PRP-Filled Collagen Tube.Journal of pain research · 2025Article
- Article
- Human birth tissue products as a non-opioid medicine to inhibit post-surgical pain.bioRxiv : the preprint server for biology · 2024Article
- Phylogenetic analysis of mammalian SIP30 sequences indicating accelerated adaptation of functional domain in primates.Biochemistry and biophysics reports · 2024Article
- Hyperexcitability of muscle spindle afferents in jaw-closing muscles in experimental myalgia: Evidence for large primary afferents involvement in chronic pain.Experimental physiology · 2024Review
- Neuromuscular Polytrauma Pain is Resolved by Macrophage COX-2 Nanoimmunomodulation.International journal of nanomedicine · 2024Article
- Relating Spinal Injury-Induced Neuropathic Pain and Spontaneous Afferent Activity to Sleep and Respiratory Dysfunction.Journal of neurotrauma · 2023Article
- Diabetes-Induced Amplification of Nociceptive DRG Neuron Output by Upregulation of Somatic T-Type CaBiomolecules · 2023Article
- Pathophysiology of Post-Traumatic Trigeminal Neuropathic Pain.Biomolecules · 2022Review
- Differential Activation of pERK1/2 and c-Fos Following Injury to Different Regions of Primary Sensory Neuron.Life (Basel, Switzerland) · 2022Article
- Quantum Mechanical Aspects in the Pathophysiology of Neuropathic Pain.Brain sciences · 2022Article
42 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors.
Funding
Abstract
Intractable neuropathic pain often results from nerve injury. One immediate event in damaged nerve is a sustained increase in spontaneous afferent activity, which has a well-established role in ongoing pain. Using two rat models of neuropathic pain, the CCI and SNI models, we show that local, temporary nerve blockade of this afferent activity permanently inhibits the subsequent development of both thermal hyperalgesia and mechanical allodynia. Timing is critical-the nerve blockade must last at least 3-5 days and is effective if started immediately after nerve injury, but not if started at 10 days after injury when neuropathic pain is already established. Effective nerve blockade also prevents subsequent development of spontaneous afferent activity measured electrophysiologically. Similar results were obtained in both pain models, and with two blockade methods (200mg of a depot form bupivacaine at the injury site, or perfusion of the injured nerve just proximal to the injury site with TTX). These results indicate that early spontaneous afferent fiber activity is the key trigger for the development of pain behaviors, and suggest that spontaneous activity may be required for many of the later changes in the sensory neurons, spinal cord, and brain observed in neuropathic pain models. Many pre-clinical and clinical studies of pre-emptive analgesia have used much shorter duration of blockade, or have not started immediately after the injury. Our results suggest that effective pre-emptive analgesia can be achieved only when nerve block is administered early after injury and lasts several days.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.