title: Sensitization of neonatal rat lumbar motoneuron by the inflammatory pain mediator bradykinin.
abstract: Bradykinin (Bk) is a potent inflammatory mediator that causes hyperalgesia. The action of Bk on the sensory system is well documented but its effects on motoneurons, the final pathway of the motor system, are unknown. By a combination of patch-clamp recordings and two-photon calcium imaging, we found that Bk strongly sensitizes spinal motoneurons. Sensitization was characterized by an increased ability to generate self-sustained spiking in response to excitatory inputs. Our pharmacological study described a dual ionic mechanism to sensitize motoneurons, including inhibition of a barium-sensitive resting K(+) conductance and activation of a nonselective cationic conductance primarily mediated by Na(+). Examination of the upstream signaling pathways provided evidence for postsynaptic activation of B2 receptors, G protein activation of phospholipase C, InsP3 synthesis, and calmodulin activation. This study questions the influence of motoneurons in the assessment of hyperalgesia since the withdrawal motor reflex is commonly used as a surrogate pain model.
authors.affiliation: Institut de Neurosciences de la Timone (UMR7289), Aix-Marseille Université and CNRS, Marseille, France.
authors.forename: Mouloud
authors.initials: M
authors.lastname: Bouhadfane
authors.affiliation: Institut de Neuroscience des Systèmes (UMR1106), Aix Marseille Université and INSERM, Marseille, France.
authors.forename: Attila
authors.initials: A
authors.lastname: Kaszás
authors.affiliation: Two-Photon Imaging Center, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary.
authors.forename: Balázs
authors.initials: B
authors.lastname: Rózsa
authors.affiliation: Department of Neurobiology and Behavior, Cornell University, Ithaca, United States.
authors.forename: Ronald M
authors.initials: RM
authors.lastname: Harris-Warrick
authors.affiliation: Institut de Neurosciences de la Timone (UMR7289), Aix-Marseille Université and CNRS, Marseille, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Vinay
authors.affiliation: Institut de Neurosciences de la Timone (UMR7289), Aix-Marseille Université and CNRS, Marseille, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Brocard
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000831:Animals, Newborn; D001920:Bradykinin / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002147:Calmodulin / Q000235:genetics / Q000378:metabolism; D005260:Female; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015870:Gene Expression; D006930:Hyperalgesia / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D007249:Inflammation / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015544:Inositol 1,4,5-Trisphosphate / Q000096:biosynthesis; D008297:Male; D057054:Molecular Imaging; D009046:Motor Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010146:Pain / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D043782:Receptor, Bradykinin B2 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010738:Type C Phospholipases / Q000235:genetics / Q000378:metabolism
chemical_list: D002147:Calmodulin; D015221:Potassium Channels; D043782:Receptor, Bradykinin B2; D015222:Sodium Channels; D015544:Inositol 1,4,5-Trisphosphate; D010738:Type C Phospholipases; D001920:Bradykinin; D002118:Calcium
keywords: hyperalgesia; motoneuron; neuroscience; pain; rat; spinal cord