{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T01:58:58Z","timestamp":1771466338956,"version":"3.50.1"},"reference-count":27,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,10,2]],"date-time":"2017-10-02T00:00:00Z","timestamp":1506902400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,10,2]],"date-time":"2017-10-02T00:00:00Z","timestamp":1506902400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Perception of space has been guiding effective therapeutic interventions in a number of unilateral chronic pain conditions. However little is known about how trigeminal neuralgia (TN), a condition in which trigeminal stimulation triggers paroxysmal facial pain, affects defensive peripersonal space (DPPS), the portion of space surrounding the body within which defensive responses are enhanced. Given that TN is unilateral, in TN patients the DPPS of the face might not be horizontally symmetric as in pain-free individuals, but instead larger around the affected side. We tested this <jats:italic>a priori<\/jats:italic> hypothesis by measuring the proximity-dependent modulation of the hand-blink reflex. Stimuli delivered to the hand ipsilateral to TN elicited a stronger blink, particularly when it was measured from the eye ipsilateral to TN and the hand was\u00a0closer to the face. Geometric modelling revealed (1) that DPPS was larger on the side of space ipsilateral to TN, and (2) this asymmetry was consequent to an increased estimated potential of sensory events to cause harm when they occur ipsilaterally to TN. These observations demonstrate that neural mechanisms underlying body protection in TN are adjusted to reduce the likelihood that external events evoke the painful paroxysm typical of this condition.<\/jats:p>","DOI":"10.1038\/s41598-017-12466-5","type":"journal-article","created":{"date-parts":[[2017,9,26]],"date-time":"2017-09-26T08:59:16Z","timestamp":1506416356000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Pain outside the body: defensive peripersonal space deformation in trigeminal neuralgia"],"prefix":"10.1038","volume":"7","author":[{"given":"R. J.","family":"Bufacchi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C. F.","family":"Sambo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G.","family":"Di Stefano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G.","family":"Cruccu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G. D.","family":"Iannetti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2017,10,2]]},"reference":[{"key":"12466_CR1","doi-asserted-by":"publisher","first-page":"845","DOI":"10.1016\/j.neuropsychologia.2005.09.009","volume":"44","author":"MS Graziano","year":"2006","unstructured":"Graziano, M. S. & Cooke, D. F. Parieto-frontal interactions, personal space, and defensive behavior. Neuropsychologia \n                           44, 845\u2013859 (2006).","journal-title":"Neuropsychologia"},{"key":"12466_CR2","doi-asserted-by":"publisher","first-page":"991","DOI":"10.1016\/j.neubiorev.2010.10.016","volume":"35","author":"DC Blanchard","year":"2011","unstructured":"Blanchard, D. C., Griebel, G., Pobbe, R. & Blanchard, R. J. Risk assessment as an evolved threat detection and analysis process. Neurosci. Biobehav. Rev. \n                           35, 991\u2013998 (2011).","journal-title":"Neurosci. Biobehav. Rev."},{"key":"12466_CR3","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyg.2011.00205","volume":"2","author":"E Combe","year":"2011","unstructured":"Combe, E. & Fujii, N. Depth perception and defensive system activation in a 3-d environment. Front. Psychol. \n                           2, 205 (2011).","journal-title":"Front. Psychol."},{"key":"12466_CR4","doi-asserted-by":"publisher","first-page":"1079","DOI":"10.1126\/science.1144298","volume":"317","author":"D Mobbs","year":"2016","unstructured":"Mobbs, D. et al. When Fear Is Near: Threat Imminence Elicits Prefrontal\u2013 Periaqueductal Gray Shifts in Humans. Science (80-.). \n                           317, 1079\u20131083 (2016).","journal-title":"Science (80-.)."},{"key":"12466_CR5","doi-asserted-by":"publisher","first-page":"880","DOI":"10.1152\/jn.00731.2011","volume":"107","author":"CF Sambo","year":"2012","unstructured":"Sambo, C. F., Liang, M., Cruccu, G. & Iannetti, G. D. Defensive peripersonal space: the blink reflex evoked by hand stimulation is increased when the hand is near the face. J. Neurophysiol. \n                           107, 880\u2013889 (2012).","journal-title":"J. Neurophysiol."},{"key":"12466_CR6","doi-asserted-by":"publisher","first-page":"12921","DOI":"10.1523\/JNEUROSCI.0607-12.2012","volume":"32","author":"CF Sambo","year":"2012","unstructured":"Sambo, C. F., Forster, B., Williams, S. C. & Iannetti, G. D. To blink or not to blink: fine cognitive tuning of the defensive peripersonal space. J. Neurosci. \n                           32, 12921\u201312927 (2012).","journal-title":"J. Neurosci."},{"key":"12466_CR7","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1152\/jn.1996.76.1.141","volume":"76","author":"L Fogassi","year":"1996","unstructured":"Fogassi, L. et al. Coding of peripersonal space in inferior premotor cortex (area F4). J. Neurophysiol. \n                           76, 141\u201357 (1996).","journal-title":"J. Neurophysiol."},{"key":"12466_CR8","doi-asserted-by":"publisher","first-page":"782","DOI":"10.1016\/j.neuropsychologia.2009.10.010","volume":"48","author":"E Macaluso","year":"2010","unstructured":"Macaluso, E. & Maravita, A. The representation of space near the body through touch and vision. Neuropsychologia \n                           48, 782\u201395 (2010).","journal-title":"Neuropsychologia"},{"key":"12466_CR9","doi-asserted-by":"publisher","first-page":"3317","DOI":"10.1152\/jn.00513.2003","volume":"90","author":"DF Cooke","year":"2003","unstructured":"Cooke, D. F. & Graziano, M. S. Defensive movements evoked by air puff in monkeys. J. Neurophysiol. \n                           90, 3317\u201329 (2003).","journal-title":"J. Neurophysiol."},{"key":"12466_CR10","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1152\/jn.00614.2005","volume":"95","author":"D Lloyd","year":"2005","unstructured":"Lloyd, D., Morrison, I. & Roberts, N. Role for Human Posterior Parietal Cortex in Visual Processing of Aversive Objects in Peripersonal Space. J. Neurophysiol. \n                           95, 205\u2013214 (2005).","journal-title":"J. Neurophysiol."},{"key":"12466_CR11","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1016\/j.neuropsychologia.2014.10.022","volume":"70","author":"J Cl\u00e9ry","year":"2015","unstructured":"Cl\u00e9ry, J., Guipponi, O., Wardak, C. & Ben Hamed, S. Neuronal bases of peripersonal and extrapersonal spaces, their plasticity and their dynamics: Knowns and unknowns. Neuropsychologia \n                           70, 313\u2013326 (2015).","journal-title":"Neuropsychologia"},{"key":"12466_CR12","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1152\/jn.00691.2015","volume":"115","author":"RJ Bufacchi","year":"2016","unstructured":"Bufacchi, R. J., Liang, M., Griffin, L. D. & Iannetti, G. D. A geometric model of defensive peripersonal space. J. Neurophysiol. \n                           115, 218\u2013225 (2016).","journal-title":"J. Neurophysiol."},{"key":"12466_CR13","doi-asserted-by":"publisher","first-page":"14225","DOI":"10.1523\/JNEUROSCI.0706-13.2013","volume":"33","author":"CF Sambo","year":"2013","unstructured":"Sambo, C. F. & Iannetti, G. D. Better safe than sorry? The safety margin surrounding the body is increased by anxiety. J. Neurosci. \n                           33, 14225\u201330 (2013).","journal-title":"J. Neurosci."},{"key":"12466_CR14","doi-asserted-by":"publisher","first-page":"1013","DOI":"10.1111\/j.1468-1331.2008.02185.x","volume":"15","author":"G Cruccu","year":"2008","unstructured":"Cruccu, G. et al. AAN-EFNS guidelines on trigeminal neuralgia management. Eur. J. Neurol. \n                           15, 1013\u20131028 (2008).","journal-title":"Eur. J. Neurol."},{"key":"12466_CR15","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1212\/WNL.0000000000002840","volume":"87","author":"G Cruccu","year":"2016","unstructured":"Cruccu, G. et al. Trigeminal neuralgia: New classification and diagnostic grading for practice and research. Neurology \n                           87, 220\u2013228 (2016).","journal-title":"Neurology"},{"key":"12466_CR16","doi-asserted-by":"publisher","DOI":"10.1177\/0333102416687280","volume":"37","author":"S Maarbjerg","year":"2017","unstructured":"Maarbjerg, S., Di Stefano, G., Bendtsen, L. & Cruccu, G. Trigeminal neuralgia \u2013 diagnosis and treatment. Cephalalgia \n                           37, 33310241668728 (2017).","journal-title":"Cephalalgia"},{"key":"12466_CR17","doi-asserted-by":"publisher","first-page":"1574","DOI":"10.1111\/head.12441","volume":"54","author":"S Maarbjerg","year":"2014","unstructured":"Maarbjerg, S., Gozalov, A., Olesen, J. & Bendtsen, L. Trigeminal neuralgia-a prospective systematic study of clinical characteristics in 158 patients. Headache \n                           54, 1574\u20131582 (2014).","journal-title":"Headache"},{"key":"12466_CR18","doi-asserted-by":"publisher","first-page":"1464","DOI":"10.1016\/j.pain.2014.04.020","volume":"155","author":"G Antonini","year":"2014","unstructured":"Antonini, G. et al. Magnetic resonance imaging contribution for diagnosing symptomatic neurovascular contact in classical trigeminal neuralgia: A blinded case-control study and meta-analysis. Pain \n                           155, 1464\u20131471 (2014).","journal-title":"Pain"},{"key":"12466_CR19","doi-asserted-by":"publisher","first-page":"1877","DOI":"10.1093\/brain\/120.10.1877","volume":"120","author":"J Valls-Sol\u00e9","year":"1997","unstructured":"Valls-Sol\u00e9, J., Valldeoriola, F., Tolosa, E. & Marti, M. Distinctive abnormalities of facial reflexes in patients with progressive supranuclear palsy. Brain \n                           120, 1877\u20131883 (1997).","journal-title":"Brain"},{"key":"12466_CR20","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1093\/brain\/121.2.281","volume":"121","author":"H Miwa","year":"1998","unstructured":"Miwa, H., Nohara, C., Hotta, M., Shimo, Y. & Amemiya, K. Somatosensory-evoked blink response: Investigation of the physiological mechanism. Brain \n                           121, 281\u2013291 (1998).","journal-title":"Brain"},{"key":"12466_CR21","doi-asserted-by":"publisher","first-page":"R1133","DOI":"10.1016\/j.cub.2016.09.025","volume":"26","author":"RJ Bufacchi","year":"2016","unstructured":"Bufacchi, R. J. & Iannetti, G. D. Gravitational cues modulate the shape of defensive peripersonal space. Curr. Biol. \n                           26, R1133\u2013R1134 (2016).","journal-title":"Curr. Biol."},{"key":"12466_CR22","doi-asserted-by":"publisher","DOI":"10.1038\/srep19353","volume":"6","author":"C Fossataro","year":"2016","unstructured":"Fossataro, C., Sambo, C. F., Garbarini, F. & Iannetti, G. D. Interpersonal interactions and empathy modulate perception of threat and defensive responses. Sci. Rep. \n                           6, 19353 (2016).","journal-title":"Sci. Rep."},{"key":"12466_CR23","doi-asserted-by":"publisher","first-page":"1041","DOI":"10.1016\/j.mri.2008.01.011","volume":"26","author":"A Mouraux","year":"2008","unstructured":"Mouraux, A. & Iannetti, G. D. Across-trial averaging of event-related EEG responses and beyond. Magn. Reson. Imaging \n                           26, 1041\u20131054 (2008).","journal-title":"Magn. Reson. Imaging"},{"key":"12466_CR24","doi-asserted-by":"publisher","DOI":"10.1177\/0333102417721677","volume":"0","author":"G Di Stefano","year":"2017","unstructured":"Di Stefano, G., Maarbjerg, S., Nurmikko, T., Truini, A. & Cruccu, G. Triggering trigeminal neuralgia. Cephalalgia \n                           0, 33310241772167 (2017).","journal-title":"Cephalalgia"},{"key":"12466_CR25","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1152\/jn.1980.43.2.332","volume":"43","author":"E Carstens","year":"1980","unstructured":"Carstens, E., Klumpp, D. & Zimmermann, M. Differential inhibitory effects of medial and lateral midbrain stimulation on spinal neuronal discharges to noxious skin heating in the cat. J Neurophysiol \n                           43, 332\u2013342 (1980).","journal-title":"J Neurophysiol"},{"key":"12466_CR26","doi-asserted-by":"publisher","first-page":"R164","DOI":"10.1016\/j.cub.2013.01.047","volume":"23","author":"P Haggard","year":"2013","unstructured":"Haggard, P., Iannetti, G. D. & Longo, M. R. Spatial sensory organization and body representation in pain perception. Curr. Biol. \n                           23, R164\u2013R176 (2013).","journal-title":"Curr. Biol."},{"key":"12466_CR27","doi-asserted-by":"publisher","first-page":"3676","DOI":"10.1093\/brain\/aws297","volume":"135","author":"GL Moseley","year":"2012","unstructured":"Moseley, G. L., Gallace, A. & Iannetti, G. D. Spatially defined modulation of skin temperature and hand ownership of both hands in patients with unilateral complex regional pain syndrome. Brain \n                           135, 3676\u20133686 (2012).","journal-title":"Brain"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-12466-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-12466-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-12466-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,23]],"date-time":"2022-12-23T11:37:29Z","timestamp":1671795449000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-12466-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,10,2]]},"references-count":27,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2017,12]]}},"alternative-id":["12466"],"URL":"https:\/\/doi.org\/10.1038\/s41598-017-12466-5","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,10,2]]},"assertion":[{"value":"23 May 2017","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 September 2017","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 October 2017","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare that they have no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"12487"}}