title: Spinal cord compression injury in lysophosphatidic acid 1 receptor-null mice promotes maladaptive pronociceptive descending control.
abstract: BACKGROUND
  Although activation of the lysophosphatidic acid receptor 1 (LPA1) is known to mediate pronociceptive effects in peripheral pain models, the role of this receptor in the modulation of spinal nociception following spinal cord injury (SCI) is unknown.
  
  
  OBJECTIVE
  In this study, LPA1 regulation of spinal excitability mediated by supraspinal descending antinociceptive control systems was assessed following SCI in both wild-type (WT) and maLPA1-null receptor mice.
  
  
  METHODS
  The effect of a T8 spinal compression in WT and maLPA1-null mice was assessed up to 1 month after SCI using histological, immunohistochemical and behavioural techniques analysis including electrophysiological recording of noxious toes-Tibialis Anterior (TA) stimulus-response reflex activity. The effect of a T3 paraspinal transcutaneous electrical conditioning stimulus on TA noxious reflex temporal summation was also assessed.
  
  
  RESULTS
  Histological analysis demonstrated greater dorsolateral funiculus damage after SCI in maLPA1-null mice, without a change in the stimulus-response function of the TA noxious reflex when compared to WT mice. While T3 conditioning stimulation in the WT group inhibited noxious TA reflex temporal summation after SCI, this stimulus strongly excited TA reflex temporal summation in maLPA1-null mice. The functional switch from descending inhibition to maladaptive facilitation of central excitability of spinal nociception demonstrated in maLPA1-null mice after SCI was unrelated to a general change in reflex activity.
  
  
  CONCLUSIONS
  These data suggest that the LPA1 receptor is necessary for inhibition of temporal summation of noxious reflex activity, partly mediated via long-tract descending modulatory systems acting at the spinal level.
authors.affiliation: Unidad de Gestión Clínica Intercentros de Neurociencias, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospitales Universitarios Regional de Málaga y Virgen de la Victoria, Málaga, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Suardíaz
authors.affiliation: Sensorimotor Function Group, Hospital Nacional de Parapléjicos, Toledo, Spain.
authors.forename: I
authors.initials: I
authors.lastname: Galan-Arriero
authors.affiliation: Sensorimotor Function Group, Hospital Nacional de Parapléjicos, Toledo, Spain.
authors.forename: G
authors.initials: G
authors.lastname: Avila-Martin
authors.affiliation: Unidad de Gestión Clínica Intercentros de Neurociencias, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospitales Universitarios Regional de Málaga y Virgen de la Victoria, Málaga, Spain.
authors.forename: G
authors.initials: G
authors.lastname: Estivill-Torrús
authors.affiliation: Unidad de Gestión Clínica de Salud Mental, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospitales Universitarios Regional de Malaga y Virgen de la Victoria, Malaga, Spain.
authors.forename: F R
authors.initials: FR
authors.lastname: de Fonseca
authors.affiliation: Department of Molecular and Cellular Neuroscience, Dorris Neuroscience Centre The Scripps Research Institute, La Jolla, USA.
authors.forename: J
authors.initials: J
authors.lastname: Chun
authors.affiliation: Grupo de Investigación en Fisioterapia Toledo (GIFTO), E.U.E. Fisioterapia de Toledo, Universidad de Castilla la Mancha, USA.
authors.forename: J
authors.initials: J
authors.lastname: Gómez-Soriano
authors.affiliation: Neurorehabilitation Group, Instituto Cajal, Council for Scientific Research (CSIC), Madrid, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Bravo-Esteban
authors.affiliation: Sensorimotor Function Group, Hospital Nacional de Parapléjicos, Toledo, Spain.|Stoke Mandeville Spinal Research, National Spinal Injuries Centre, Aylesbury, UK.
authors.forename: J
authors.initials: J
authors.lastname: Taylor
mesh_terms: D000818:Animals; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000503:physiopathology; D059225:Nociception; D010146:Pain / Q000235:genetics / Q000503:physiopathology*; D049368:Receptors, Lysophosphatidic Acid / Q000235:genetics*; D012018:Reflex / Q000502:physiology; D013117:Spinal Cord Compression / Q000503:physiopathology*; D013119:Spinal Cord Injuries / Q000503:physiopathology*
chemical_list: D049368:Receptors, Lysophosphatidic Acid