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      Journal of Pain Research (submit here)

      This international, peer-reviewed Open Access journal by Dove Medical Press focuses on reporting of high-quality laboratory and clinical findings in all fields of pain research and the prevention and management of pain. Sign up for email alerts here.

      52,235 Monthly downloads/views I 2.832 Impact Factor I 4.5 CiteScore I 1.2 Source Normalized Impact per Paper (SNIP) I 0.655 Scimago Journal & Country Rank (SJR)

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      Noradrenaline modulates mechanically evoked responses in the rat spinal dorsal horn: an in vivo patch-clamp study

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          Abstract

          Purpose: We investigated the effects of noradrenaline (NA) on physiologically evoked synaptic responses of substantia gelatinosa (SG) neurons using anesthetized animals.

          Methods: Male Sprague–Dawley rats (6–8 weeks, 200–300 g, n=21) were anesthetized. The lumbar spinal cord was exposed from L3 to L5; subsequently, the rats were fixed to a stereotaxic apparatus. The electrode was advanced at an angle of 30–45 degrees into the SG using a micromanipulator. We recorded excitatory post-synaptic currents (EPSC). Under these conditions, innocuous or noxious mechanical stimuli were applied to the receptive field of the ipsilateral hindlimb with or without NA, respectively.

          Results: NA (50 μM) pre-application induced three types of responses for pinch-evoked EPSCs. The number of neurons showing inhibition, facilitation, and no-effect was 15 (71.4%), 2 (9.5%), and 4 (19%), respectively (n=21). Pre-treatment with NA also induced three different types of responses for puff-evoked EPSC (n=21). The number of neurons showing inhibition, facilitation, and no-effect was 9 (42.9%), 9 (42.9%), and 3 (14.2%), respectively. Further, there was a significant difference in the rate distribution (inhibition, facilitation, and no change) between puff- and pinch-evoked responses.

          Conclusion: Our present data indicate that NA acts on noxious and innocuous mechanical transmission in the SG. Considering the distinct sensory inputs to the SG, the different actions of NA on the transmission of sensory information imply that NA exerts its analgesic effects in a manner more complicated than previously believed.

          Most cited references37

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          The functional organization of cutaneous low-threshold mechanosensory neurons.

          Lishi Li, Michael Rutlin, Victoria Abraira … (2011)
          Innocuous touch of the skin is detected by distinct populations of neurons, the low-threshold mechanoreceptors (LTMRs), which are classified as Aβ-, Aδ-, and C-LTMRs. Here, we report genetic labeling of LTMR subtypes and visualization of their relative patterns of axonal endings in hairy skin and the spinal cord. We found that each of the three major hair follicle types of trunk hairy skin (guard, awl/auchene, and zigzag hairs) is innervated by a unique and invariant combination of LTMRs; thus, each hair follicle type is a functionally distinct mechanosensory end organ. Moreover, the central projections of Aβ-, Aδ-, and C-LTMRs that innervate the same or adjacent hair follicles form narrow LTMR columns in the dorsal horn. These findings support a model of mechanosensation in which the activities of Aβ-, Aδ-, and C-LTMRs are integrated within dorsal horn LTMR columns and processed into outputs that underlie the perception of myriad touch sensations. Copyright © 2011 Elsevier Inc. All rights reserved.
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            Dorsal Horn Parvalbumin Neurons Are Gate-Keepers of Touch-Evoked Pain after Nerve Injury

            Hugues Petitjean, Sophie Pawlowski, Steven Fraine … (2015)
            SUMMARY Neuropathic pain is a chronic debilitating disease that results from nerve damage, persists long after the injury has subsided, and is characterized by spontaneous pain and mechanical hypersensitivity. Although loss of inhibitory tone in the dorsal horn of the spinal cord is a major contributor to neuropathic pain, the molecular and cellular mechanisms underlying this disinhibition are unclear. Here, we combined pharmacogenetic activation and selective ablation approaches in mice to define the contribution of spinal cord parvalbumin (PV)-expressing inhibitory interneurons in naive and neuropathic pain conditions. Ablating PV neurons in naive mice produce neuropathic pain-like mechanical allodynia via disinhibition of PKCγ excitatory interneurons. Conversely, activating PV neurons in nerve-injured mice alleviates mechanical hypersensitivity. These findings indicate that PV interneurons are modality-specific filters that gate mechanical but not thermal inputs to the dorsal horn and that increasing PV inter-neuron activity can ameliorate the mechanical hypersensitivity that develops following nerve injury.
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              Populations of inhibitory and excitatory interneurons in lamina II of the adult rat spinal dorsal horn revealed by a combined electrophysiological and anatomical approach

              Toshiharu Yasaka, Sheena Y.X. Tiong, David Hughes … (2010)
              Lamina II contains a large number of interneurons involved in modulation and transmission of somatosensory (including nociceptive) information. However, its neuronal circuitry is poorly understood due to the difficulty of identifying functional populations of interneurons. This information is important for understanding nociceptive processing and for identifying changes that underlie chronic pain. In this study, we compared morphology, neurotransmitter content, electrophysiological and pharmacological properties for 61 lamina II neurons recorded in slices from adult rat spinal cord. Morphology was related to transmitter content, since islet cells were GABAergic, while radial and most vertical cells were glutamatergic. However, there was considerable diversity among the remaining cells, some of which could not be classified morphologically. Transmitter phenotype was related to firing pattern, since most (18/22) excitatory cells, but few (2/23) inhibitory cells had delayed, gap or reluctant patterns, which are associated with A-type potassium (I A) currents. Somatostatin was identified in axons of 14/24 excitatory neurons. These had variable morphology, but most of those tested showed delayed-firing. Excitatory interneurons are therefore likely to contribute to pain states associated with synaptic plasticity involving I A currents. Although noradrenaline and serotonin evoked outward currents in both inhibitory and excitatory cells, somatostatin produced these currents only in inhibitory neurons, suggesting that its pro-nociceptive effects are mediated by disinhibition. Our results demonstrate that certain distinctive populations of inhibitory and excitatory interneuron can be recognised in lamina II. Combining this approach with identification of other neurochemical markers should allow further clarification of neuronal circuitry in the superficial dorsal horn.
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                Author and article information

                Journal
                Journal ID (nlm-ta): J Pain Res
                Journal ID (iso-abbrev): J Pain Res
                Journal ID (publisher-id): JPR
                Journal ID (pmc): jpainres
                Title: Journal of Pain Research
                Publisher: Dove
                ISSN (Electronic): 1178-7090
                Publication date (Electronic): 17 April 2019
                Publication date Collection: 2019
                Volume: 12
                Pages: 1269-1278
                Affiliations
                [1 ]Department of Orthopaedic Surgery, Faculty of Medicine, Saga University , Saga, Japan
                [2 ]Department of Physical Therapy, Kumamoto Health Science University , Kumamoto, Japan
                [3 ]Department of Immunology, Graduate School of Medical and Dental SciencesKagoshima University , Kagoshima, Japan
                [4 ]Department of Applied Pharmacology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama , Toyama, Japan
                [5 ]Department of Integrative Physiology, Graduate School of Medical Sciences, Kyushu University , Fukuoka, Japan
                [6 ]Nakamura Hospital , Nogata, Fukuoka, Japan
                Author notes
                Correspondence: Motoki SonohataDepartment of Orthopaedic Surgery, Faculty of Medicine, Saga University , 5-1-1, Nabeshima Saga-shi, Saga849-8501, JapanTel +81 095 234 2343Fax +81 095 234 2059Email epc9719@ 123456yahoo.co.jp
                [*]

                These authors contributed equally to this work

                Article
                Publisher ID: 181210
                DOI: 10.2147/JPR.S181210
                PMC ID: 6489873
                SO-VID: 06f607d8-4671-4726-a9b9-9ba4035c6a76
                Copyright © © 2019 Sonohata et al.
                License:

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                Date received : 23 July 2018
                Date accepted : 14 February 2019
                Page count
                Figures: 5, References: 47, Pages: 10
                Categories
                Subject: Original Research

                ScienceOpen disciplines: Anesthesiology & Pain management
                Keywords: noradrenaline,in vivo patch-clamp technique,touch,pain,spinal dorsal horn
                Data availability:
                ScienceOpen disciplines: Anesthesiology & Pain management
                Keywords: noradrenaline, in vivo patch-clamp technique, touch, pain, spinal dorsal horn

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