ArticlePain2011
Engagement of descending inhibition from the rostral ventromedial medulla protects against chronic neuropathic pain.
Article in Pain, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 106 papers, 1 of them a synthesis that pooled it.
What it found
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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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
106 citing papers in PubMed, 1 synthesis or guideline pooled it, 210 citations in OpenAlex.
- Central changes associated with chronic pelvic pain and endometriosis.Human reproduction updatePooled it
- Trial
- A Randomized Controlled Trial on the Effect of Tapentadol and Morphine on Conditioned Pain Modulation in Healthy Volunteers.PloS one · 2015Trial
- The role of mu opioid receptors on excitatory and inhibitory neurons in the rostral ventromedial medulla in neuropathic pain.bioRxiv : the preprint server for biology · 2026Article
- PainDETECT as a Potential Tool for Personalized Medicine: Predicting Outcome One Year After Knee Arthroplasty.Mayo Clinic proceedings. Innovations, quality & outcomes · 2025Article
- Focal Adhesion Kinase Inhibition Ameliorates Burn Injury-Induced Chronic Pain in Rats.Molecular neurobiology · 2025Article
- Modulating neuroplasticity for chronic pain relief: noninvasive neuromodulation as a promising approach.Experimental & molecular medicine · 2025Review
- Unveiling the Applications of Phytoconstituents in Neuropathic Pain.Central nervous system agents in medicinal chemistry · 2025Review
- Investigating the effects of artificial baroreflex stimulation on pain perception: A comparative study in no-pain and chronic low back pain individuals.The Journal of physiology · 2024Article
- The 'in's and out's' of descending pain modulation from the rostral ventromedial medulla.Trends in neurosciences · 2024Review
- Opposing Effects on Descending Control of Nociception by µ and κ Opioid Receptors in the Anterior Cingulate Cortex.Anesthesiology · 2024Article
- IUPHAR review- Preclinical models of neuropathic pain: Evaluating multifunctional properties of natural cannabinoid receptors ligands.Pharmacological research · 2024Review
- Peripheral Neuroinflammation and Pain: How Acute Pain Becomes Chronic.Current neuropharmacology · 2024Review
- Endometriosis-Related Chronic Pelvic Pain.Biomedicines · 2023Review
- Descending Facilitation of Nociceptive Transmission From the Rostral Ventromedial Medulla Contributes to Hyperalgesia in Mice with Sickle Cell Disease.Neuroscience · 2023Article
- The Role of The Rostral Ventromedial Medulla in Stress Responses.Brain sciences · 2023Review
- Neuropathic pain; what we know and what we should do about it.Frontiers in pain research (Lausanne, Switzerland) · 2023Review
- Glutamatergic systems in neuropathic pain and emerging non-opioid therapies.Pharmacological research · 2022Review
- Ascertaining Design and Implementation Requirements for a Perioperative Neurocognitive Training Intervention for the Prevention of Persistent Pain After Surgery.Pain medicine (Malden, Mass.) · 2022Article
- Medullary kappa-opioid receptor neurons inhibit pain and itch through a descending circuit.Brain : a journal of neurology · 2022Article
46 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 2 countries.
Funding
Abstract
A puzzling observation is why peripheral nerve injury results in chronic pain in some, but not all, patients. We explored potential mechanisms that may prevent the expression of chronic pain. Sprague Dawley (SD) or Holtzman (HZ) rats showed no differences in baseline sensory thresholds or responses to inflammatory stimuli. However, spinal nerve ligation (SNL)-induced tactile allodynia occurred in approximately 85% of SD and 50% of HZ rats, respectively. No apparent differences were observed in a survey of dorsal root ganglion or spinal neuropathic markers after SNL regardless of allodynic phenotype. SNL-induced allodynia was reversed by administration of lidocaine within the rostral ventromedial medulla (RVM), a site that integrates descending pain modulation via pain inhibitory (ie, OFF) and excitatory (ie, ON) cells. However, in SD or HZ rats with SNL but without allodynia, RVM lidocaine precipitated allodynia. Additionally, RVM lidocaine produced conditioned place preference in allodynic SD or HZ rats but conditioned place aversion in nonallodynic HZ rats. Similarly, RVM U69,593 (kappa opioid agonist) or blockade of spinal α(2) adrenergic receptors precipitated allodynia in previously nonallodynic HZ rats with SNL. All rats showed an equivalent first-phase formalin responses. However, HZ rats had reduced second-phase formalin behaviors along with fewer RVM OFF cell pauses and RVM ON cell bursts. Thus, expression of nerve injury-induced pain may ultimately depend on descending modulation. Engagement of descending inhibition protects in the transition from acute to chronic pain. These unexpected findings might provide a mechanistic explanation for medications that engage descending inhibition or mimic its consequences.
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Registered trials
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.