{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T04:56:47Z","timestamp":1791349007940,"version":"4.3.1"},"reference-count":73,"publisher":"Society for Neuroscience","issue":"8","license":[{"start":{"date-parts":[[2009,8,25]],"date-time":"2009-08-25T00:00:00Z","timestamp":1251158400000},"content-version":"vor","delay-in-days":181,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Neurosci."],"published-print":{"date-parts":[[2009,2,25]]},"abstract":"<jats:p>Dynamic mechanical allodynia is a widespread and intractable symptom of neuropathic pain for which there is a lack of effective therapy. We recently provided a novel perspective on the mechanisms of this symptom by showing that a simple switch in trigeminal glycine synaptic inhibition can turn touch into pain by unmasking innocuous input to superficial dorsal horn nociceptive specific neurons through a local excitatory, NMDA-dependent neural circuit involving neurons expressing the gamma isoform of protein kinase C. Here, we further investigated the clinical relevance and processing of glycine disinhibition. First, we showed that glycine disinhibition with strychnine selectively induced dynamic but not static mechanical allodynia. The induced allodynia was resistant to morphine. Second, morphine did not prevent the activation of the neural circuit underlying allodynia as shown by study of Fos expression and extracellular-signal regulated kinase phosphorylation in dorsal horn neurons. Third, in contrast to intradermal capsaicin injections, light, dynamic mechanical stimuli applied under disinhibition did not produce neurokinin 1 (NK1) receptor internalization in dorsal horn neurons. Finally, light, dynamic mechanical stimuli applied under disinhibition induced Fos expression only in neurons that did not express NK1 receptor. To summarize, the selectivity and morphine resistance of the glycine-disinhibition paradigm adequately reflect the clinical characteristics of dynamic mechanical allodynia. The present findings thus reveal the involvement of a selective dorsal horn circuit in dynamic mechanical allodynia, which operates through superficial lamina nociceptive-specific neurons that do not bear NK1 receptor and provide an explanation for the differences in the pharmacological sensitivity of neuropathic pain symptoms.<\/jats:p>","DOI":"10.1523\/jneurosci.3923-08.2009","type":"journal-article","created":{"date-parts":[[2009,2,25]],"date-time":"2009-02-25T13:34:19Z","timestamp":1235568859000},"page":"2519-2527","source":"Crossref","is-referenced-by-count":116,"title":["Glycine Inhibitory Dysfunction Induces a Selectively Dynamic, Morphine-Resistant, and Neurokinin 1 Receptor- Independent Mechanical Allodynia"],"prefix":"10.1523","volume":"29","author":[{"given":"Lo\u00efs S.","family":"Miraucourt","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xavier","family":"Moisset","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Radhouane","family":"Dallel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel L.","family":"Voisin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"393","published-online":{"date-parts":[[2009,2,25]]},"reference":[{"key":"2023041303365344000_29.8.2519.1","doi-asserted-by":"publisher","DOI":"10.1038\/nn778"},{"key":"2023041303365344000_29.8.2519.2","doi-asserted-by":"crossref","first-page":"1379","DOI":"10.1152\/jn.1999.81.3.1379","article-title":"Primary afferent fibers that contribute to increased substance P receptor internalization in the spinal cord after injury","volume":"81","author":"Allen","year":"1999","journal-title":"J Neurophysiol"},{"key":"2023041303365344000_29.8.2519.3","doi-asserted-by":"crossref","unstructured":"Baccei M Fitzgerald M (2006) in Wall and Melzack's textbook of pain, Development of pain pathways and mechanisms, eds McMahon SB Koltzenburg M (Churchill Livingstone, Oxford), pp 143\u2013158.","DOI":"10.1016\/B0-443-07287-6\/50013-8"},{"key":"2023041303365344000_29.8.2519.4","doi-asserted-by":"publisher","DOI":"10.1038\/ncpneuro0113"},{"key":"2023041303365344000_29.8.2519.5","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(90)91519-M"},{"key":"2023041303365344000_29.8.2519.6","doi-asserted-by":"publisher","DOI":"10.1016\/0024-3205(85)90523-5"},{"key":"2023041303365344000_29.8.2519.7","doi-asserted-by":"crossref","first-page":"1981","DOI":"10.1097\/00001756-199510010-00007","article-title":"Characterization of the antiallodynic efficacy of morphine in a model of neuropathic pain in rats","volume":"6","author":"Bian","year":"1995","journal-title":"Neuroreport"},{"key":"2023041303365344000_29.8.2519.8","doi-asserted-by":"publisher","DOI":"10.1002\/cne.903560302"},{"key":"2023041303365344000_29.8.2519.9","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2006.09.021"},{"key":"2023041303365344000_29.8.2519.10","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3959(88)90027-9"},{"key":"2023041303365344000_29.8.2519.11","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(93)90167-L"},{"key":"2023041303365344000_29.8.2519.12","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3959(01)00283-4"},{"key":"2023041303365344000_29.8.2519.13","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2007.09.017"},{"key":"2023041303365344000_29.8.2519.14","doi-asserted-by":"publisher","DOI":"10.1038\/nature04223"},{"key":"2023041303365344000_29.8.2519.15","doi-asserted-by":"crossref","first-page":"3529","DOI":"10.1523\/JNEUROSCI.18-10-03529.1998","article-title":"Morphine administered in the substantia gelatinosa of the spinal trigeminal nucleus caudalis inhibits nociceptive activities in the spinal trigeminal nucleus oralis","volume":"18","author":"Dallel","year":"1998","journal-title":"J Neurosci"},{"key":"2023041303365344000_29.8.2519.16","doi-asserted-by":"crossref","unstructured":"Devor M (2006) in Wall and Melzack's textbook of pain, Response of nerves to injury in relation to neuropathic pain, eds McMahon SB Koltzenburg M (Churchill Livingstone, Oxford), pp 905\u2013927.","DOI":"10.1016\/B0-443-07287-6\/50063-1"},{"key":"2023041303365344000_29.8.2519.17","doi-asserted-by":"crossref","unstructured":"Dickenson AH Kieffer B (2006) in Wall and Melzack's textbook of pain, Opiates: basic mechanisms, eds McMahon SB Koltzenburg M (Churchill Livingstone, Oxford), pp 427\u2013442.","DOI":"10.1016\/B0-443-07287-6\/50032-1"},{"key":"2023041303365344000_29.8.2519.18","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3959(86)90044-8"},{"key":"2023041303365344000_29.8.2519.19","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3959(98)00239-5"},{"key":"2023041303365344000_29.8.2519.20","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3959(99)00111-6"},{"key":"2023041303365344000_29.8.2519.21","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1007\/BF00238730","article-title":"The pharmacology of the inhibition of dorsal horn neurones by impulses in myelinated cutaneous afferents in the cat","volume":"23","author":"Game","year":"1975","journal-title":"Exp Brain Res"},{"key":"2023041303365344000_29.8.2519.22","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1016\/S0022-3565(24)39091-3","article-title":"Evaluation of selective NK(1) receptor antagonist CI-1021 in animal models of inflammatory and neuropathic pain","volume":"294","author":"Gonzalez","year":"2000","journal-title":"J Pharmacol Exp Ther"},{"key":"2023041303365344000_29.8.2519.23","doi-asserted-by":"publisher","DOI":"10.1126\/science.1094925"},{"key":"2023041303365344000_29.8.2519.24","doi-asserted-by":"crossref","first-page":"7670","DOI":"10.1523\/JNEUROSCI.19-17-07670.1999","article-title":"Spinal substance P receptor expression and internalization in acute, short-term, and long-term inflammatory pain states","volume":"19","author":"Honore","year":"1999","journal-title":"J Neurosci"},{"key":"2023041303365344000_29.8.2519.25","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5401-06.2007"},{"key":"2023041303365344000_29.8.2519.26","first-page":"71","article-title":"Mitogen-activated protein kinases as potential targets for pain killers","volume":"5","author":"Ji","year":"2004","journal-title":"Curr Opin Investig Drugs"},{"key":"2023041303365344000_29.8.2519.27","doi-asserted-by":"publisher","DOI":"10.1038\/16040"},{"key":"2023041303365344000_29.8.2519.28","doi-asserted-by":"publisher","DOI":"10.1186\/1744-8069-3-27"},{"key":"2023041303365344000_29.8.2519.29","doi-asserted-by":"publisher","DOI":"10.1038\/nature06493"},{"key":"2023041303365344000_29.8.2519.30","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-200102000-00024"},{"key":"2023041303365344000_29.8.2519.31","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(76)90296-1"},{"key":"2023041303365344000_29.8.2519.32","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(76)90370-X"},{"key":"2023041303365344000_29.8.2519.33","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(95)12034-2"},{"key":"2023041303365344000_29.8.2519.34","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2004.01.010"},{"key":"2023041303365344000_29.8.2519.35","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-200205000-00020"},{"key":"2023041303365344000_29.8.2519.36","doi-asserted-by":"publisher","DOI":"10.1046\/j.1460-9568.2000.00946.x"},{"key":"2023041303365344000_29.8.2519.37","doi-asserted-by":"publisher","DOI":"10.1126\/science.7539937"},{"key":"2023041303365344000_29.8.2519.38","doi-asserted-by":"publisher","DOI":"10.1186\/1744-8069-4-25"},{"key":"2023041303365344000_29.8.2519.39","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0001116"},{"key":"2023041303365344000_29.8.2519.40","doi-asserted-by":"crossref","first-page":"6724","DOI":"10.1523\/JNEUROSCI.22-15-06724.2002","article-title":"Partial peripheral nerve injury promotes a selective loss of GABAergic inhibition in the superficial dorsal horn of the spinal cord","volume":"22","author":"Moore","year":"2002","journal-title":"J Neurosci"},{"key":"2023041303365344000_29.8.2519.41","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1259-08.2008"},{"key":"2023041303365344000_29.8.2519.42","doi-asserted-by":"crossref","first-page":"7633","DOI":"10.1523\/JNEUROSCI.15-11-07633.1995","article-title":"Substance P induced by peripheral nerve injury in primary afferent sensory neurons and its effect on dorsal column nucleus neurons","volume":"15","author":"Noguchi","year":"1995","journal-title":"J Neurosci"},{"key":"2023041303365344000_29.8.2519.43","doi-asserted-by":"crossref","first-page":"10784","DOI":"10.1523\/JNEUROSCI.23-34-10784.2003","article-title":"Opioid modulation of scratching and spinal c-fos expression evoked by intradermal serotonin","volume":"23","author":"Nojima","year":"2003","journal-title":"J Neurosci"},{"key":"2023041303365344000_29.8.2519.44","doi-asserted-by":"publisher","DOI":"10.1002\/cne.21620"},{"key":"2023041303365344000_29.8.2519.45","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1111\/j.1476-5381.1992.tb14348.x","article-title":"CP-93,129, sumatriptan, dihydroergotamine block c-fos expression within rat trigeminal nucleus caudalis caused by chemical stimulation of the meninges","volume":"106","author":"Nozaki","year":"1992","journal-title":"Br J Pharmacol"},{"key":"2023041303365344000_29.8.2519.46","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410330509"},{"key":"2023041303365344000_29.8.2519.47","unstructured":"Paxinos G Watson C (1997) The rat brain in stereotaxic coordinates (Academic, New York)."},{"key":"2023041303365344000_29.8.2519.48","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1523\/JNEUROSCI.10-01-00323.1990","article-title":"Systemic morphine suppresses noxious stimulus-evoked Fos protein-like immunoreactivity in the rat spinal cord","volume":"10","author":"Presley","year":"1990","journal-title":"J Neurosci"},{"key":"2023041303365344000_29.8.2519.49","doi-asserted-by":"crossref","first-page":"1494","DOI":"10.1152\/jn.1998.79.3.1494","article-title":"Spinal effects of bicuculline: Modulation of an allodynia-like state by an A1-receptor agonist, morphine, and an NMDA-receptor antagonist","volume":"79","author":"Reeve","year":"1998","journal-title":"J Neurophysiol"},{"key":"2023041303365344000_29.8.2519.50","doi-asserted-by":"publisher","DOI":"10.1016\/S0031-9384(99)00136-5"},{"key":"2023041303365344000_29.8.2519.51","doi-asserted-by":"publisher","DOI":"10.1016\/0024-3205(86)90164-5"},{"key":"2023041303365344000_29.8.2519.52","doi-asserted-by":"publisher","DOI":"10.1002\/cne.21311"},{"key":"2023041303365344000_29.8.2519.53","doi-asserted-by":"crossref","unstructured":"Scholz J Woolf CJ (2002) Can we conquer pain? Nat Neurosci (5 Suppl):1062\u20131067.","DOI":"10.1038\/nn942"},{"key":"2023041303365344000_29.8.2519.54","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2003.12.004"},{"key":"2023041303365344000_29.8.2519.55","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3959(94)90146-5"},{"key":"2023041303365344000_29.8.2519.56","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3959(96)03130-2"},{"key":"2023041303365344000_29.8.2519.57","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2005.06.015"},{"key":"2023041303365344000_29.8.2519.58","doi-asserted-by":"publisher","DOI":"10.1113\/eph8702351"},{"key":"2023041303365344000_29.8.2519.59","doi-asserted-by":"crossref","unstructured":"Todd AJ Koerber HR (2006) in Wall and Melzack's textbook of pain, Neuroanatomical substrate of spinal nociception, eds McMahon SB Koltzenburg M (Churchill Livingstone, Oxford), pp 73\u201390.","DOI":"10.1016\/B0-443-07287-6\/50009-6"},{"key":"2023041303365344000_29.8.2519.60","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/110.6.1509"},{"key":"2023041303365344000_29.8.2519.61","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4584-05.2006"},{"key":"2023041303365344000_29.8.2519.62","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-6147(00)01578-9"},{"key":"2023041303365344000_29.8.2519.63","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresrev.2004.07.004"},{"key":"2023041303365344000_29.8.2519.64","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2005.086520"},{"key":"2023041303365344000_29.8.2519.65","doi-asserted-by":"crossref","first-page":"2708","DOI":"10.1523\/JNEUROSCI.14-05-02708.1994","article-title":"Behavioral evidence of trigeminal neuropathic pain following chronic constriction injury to the rat's infraorbital nerve","volume":"14","author":"Vos","year":"1994","journal-title":"J Neurosci"},{"key":"2023041303365344000_29.8.2519.66","doi-asserted-by":"publisher","DOI":"10.1017\/S0140525X97261480"},{"key":"2023041303365344000_29.8.2519.67","doi-asserted-by":"publisher","DOI":"10.1002\/cne.902610109"},{"key":"2023041303365344000_29.8.2519.68","doi-asserted-by":"crossref","first-page":"441","DOI":"10.7326\/0003-4819-140-8-200404200-00010","article-title":"Pain: moving from symptom control toward mechanism-specific pharmacologic management","volume":"140","author":"Woolf","year":"2004","journal-title":"Ann Intern Med"},{"key":"2023041303365344000_29.8.2519.69","doi-asserted-by":"crossref","unstructured":"Woolf CJ Salter MW (2006) in Wall and Melzack's textbook of pain, Plasticity and pain: role of the dorsal horn, eds McMahon SB Koltzenburg M (Churchill Livingstone, Oxford), pp 91\u2013105.","DOI":"10.1016\/B0-443-07287-6\/50010-2"},{"key":"2023041303365344000_29.8.2519.70","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3959(89)90160-7"},{"key":"2023041303365344000_29.8.2519.71","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1152\/jn.1999.81.2.479","article-title":"Cardiovascular and neuronal responses to head stimulation reflect central sensitization and cutaneous allodynia in a rat model of migraine","volume":"81","author":"Yamamura","year":"1999","journal-title":"J Neurophysiol"},{"key":"2023041303365344000_29.8.2519.72","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2008.03.056"},{"key":"2023041303365344000_29.8.2519.73","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2004.12.022"}],"container-title":["The Journal of Neuroscience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1523\/JNEUROSCI.3923-08.2009","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,7]],"date-time":"2025-02-07T17:22:09Z","timestamp":1738948929000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jneurosci.org\/lookup\/doi\/10.1523\/JNEUROSCI.3923-08.2009"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,2,25]]},"references-count":73,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2009,2,25]]},"published-print":{"date-parts":[[2009,2,25]]}},"alternative-id":["10.1523\/JNEUROSCI.3923-08.2009"],"URL":"https:\/\/doi.org\/10.1523\/jneurosci.3923-08.2009","relation":{},"ISSN":["0270-6474","1529-2401"],"issn-type":[{"value":"0270-6474","type":"print"},{"value":"1529-2401","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,2,25]]}}}