ArticlePain2013
Endogenous analgesic action of the pontospinal noradrenergic system spatially restricts and temporally delays the progression of neuropathic pain following tibial nerve injury.
Article in Pain, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 86 citations in OpenAlex.
- Doxazosin Alleviates Chronic Orofacial Pain.International journal of molecular sciences · 2026Article
- Noradrenergic Pathways Involved in Micturition in an Animal Model of Hydrocephalus-Implications for Urinary Dysfunction.Biomedicines · 2024Article
- Microglia cause structural remodeling of noradrenergic axon in the trigeminal spinal subnucleus caudalis after infraorbital nerve injury in rats.Brain, behavior, & immunity - health · 2023Article
- Spinal cord vascular degeneration impairs duloxetine penetration.Frontiers in pain research (Lausanne, Switzerland) · 2023Article
- Differences in the Analgesic Effect of Opioids on Pain in Cancer Patients With Spinal Metastases.Palliative medicine reports · 2023Article
- Locus coeruleus inhibition of vibrissal responses in the trigeminal subnucleus caudalis are reduced in a diabetic mouse model.Frontiers in cellular neuroscience · 2023Article
- Activation of locus coeruleus-spinal cord noradrenergic neurons alleviates neuropathic pain in mice via reducing neuroinflammation from astrocytes and microglia in spinal dorsal horn.Journal of neuroinflammation · 2022Article
- Pain and depression comorbidity causes asymmetric plasticity in the locus coeruleus neurons.Brain : a journal of neurology · 2022Article
- Central involvement of 5-HT1A receptors in antinociception induced by photobiomodulation in animal model of neuropathic pain.Lasers in medical science · 2022Article
- The role of medial prefrontal cortex projections to locus ceruleus in mediating the sex differences in behavior in mice with inflammatory pain.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- Article
- Monoaminergic and Opioidergic Modulation of Brainstem Circuits: New Insights Into the Clinical Challenges of Pain Treatment?Frontiers in pain research (Lausanne, Switzerland) · 2021Review
- Editorial: Plasticity of Endogenous Pain Modulatory Circuits in Neuropathy.Frontiers in pain research (Lausanne, Switzerland) · 2021Article
- Spinal astrocytes in superficial laminae gate brainstem descending control of mechanosensory hypersensitivity.Nature neuroscience · 2020Article
- Attenuation of the Diffuse Noxious Inhibitory Controls in Chronic Joint Inflammatory Pain Is Accompanied by Anxiodepressive-Like Behaviors and Impairment of the Descending Noradrenergic Modulation.International journal of molecular sciences · 2020Article
- A study of cortical and brainstem mechanisms of diffuse noxious inhibitory controls in anaesthetised normal and neuropathic rats.The European journal of neuroscience · 2020Article
- MHCII-restricted T helper cells: an emerging trigger for chronic tactile allodynia after nerve injuries.Journal of neuroinflammation · 2020Review
- Opioid Activity in the Locus Coeruleus Is Modulated by Chronic Neuropathic Pain.Molecular neurobiology · 2019Article
- Rescue of Noradrenergic System as a Novel Pharmacological Strategy in the Treatment of Chronic Pain: Focus on Microglia Activation.Frontiers in pharmacology · 2019Review
- Pharmacological rationale for tapentadol therapy: a review of new evidence.Journal of pain research · 2019Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Pontospinal noradrenergic neurons form part of an endogenous analgesic system that suppresses acute pain, but there is conflicting evidence about its role in neuropathic pain. We investigated the chronology of descending noradrenergic control during the development of a neuropathic pain phenotype in rats following tibial nerve transection (TNT). A lumbar intrathecal cannula was implanted at the time of nerve injury allowing administration of selective α-adrenoceptor (α-AR) antagonists to sequentially assay their effects upon the expression of allodynia and hyperalgesia. Following TNT animals progressively developed mechanical and cold allodynia (by day 10) and subsequently heat hypersensitivity (day 17). Blockade of α2-AR with intrathecal yohimbine (30 μg) revealed earlier ipsilateral sensitization of all modalities while prazosin (30 μg, α1-AR) was without effect. Established allodynia (by day 21) was partly reversed by the re-uptake inhibitor reboxetine (5 μg, i.t.) but yohimbine no longer had any sensitising effect. This loss of effect coincided with a reduction in the descending noradrenergic innervation of the ipsilateral lumbar dorsal horn. Yohimbine reversibly unmasked contralateral hindlimb allodynia and hyperalgesia of all modalities and increased dorsal horn c-fos expression to an innocuous brush stimulus. Contralateral thermal hyperalgesia was also reversibly uncovered by yohimbine administration in a contact heat ramp paradigm in anaesthetised TNT rats. Following TNT there is an engagement of inhibitory α2-AR-mediated noradrenergic tone which completely masks contralateral and transiently suppresses the development of ipsilateral sensitization. This endogenous analgesic system plays a key role in shaping the spatial and temporal expression of the neuropathic pain phenotype after nerve injury.
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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.