title: Pacemaker neurons within newborn spinal pain circuits.
abstract: Spontaneous activity driven by "pacemaker" neurons, defined by their intrinsic ability to generate rhythmic burst firing, contributes to the development of sensory circuits in many regions of the immature CNS. However, it is unknown whether pacemaker-like neurons are present within central pain pathways in the neonate. Here, we provide evidence that a subpopulation of glutamatergic interneurons within lamina I of the rat spinal cord exhibits oscillatory burst firing during early life, which occurs independently of fast synaptic transmission. Pacemaker neurons were distinguished by a higher ratio of persistent, voltage-gated Na(+) conductance to leak membrane conductance (g(Na,P)/g(leak)) compared with adjacent, nonbursting lamina I neurons. The activation of high-threshold (N-type and L-type) voltage-gated Ca(2+) channels also facilitated rhythmic burst firing by triggering intracellular Ca(2+) signaling. Bursting neurons received direct projections from high-threshold sensory afferents but transmitted nociceptive signals with poor fidelity while in the bursting mode. The observation that pacemaker neurons send axon collaterals throughout the neonatal spinal cord raises the possibility that intrinsic burst firing could provide an endogenous drive to the developing sensorimotor networks that mediate spinal pain reflexes.
authors.affiliation: Pain Research Center, Department of Anesthesiology, University of Cincinnati Medical Center, Cincinnati, Ohio 45267, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.forename: Mark L
authors.initials: ML
authors.lastname: Baccei
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000367:Age Factors; D000596:Amino Acids / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D030801:Animals, Genetically Modified; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002614:Chelating Agents / Q000494:pharmacology; D016009:Chi-Square Distribution; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005439:Flufenamic Acid / Q000494:pharmacology; D005968:Glutamate Decarboxylase / Q000235:genetics; D018698:Glutamic Acid / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics; D066298:In Vitro Techniques; D008239:Lysine / Q000031:analogs & derivatives / Q000378:metabolism; D008297:Male; D009415:Nerve Net / Q000502:physiology*; D009434:Neural Pathways / Q000502:physiology; D009474:Neurons / Q000145:classification / Q000502:physiology*; D018408:Patch-Clamp Techniques / Q000379:methods; D010487:Periaqueductal Gray / Q000502:physiology; D010507:Periodicity; D026902:Potassium Channel Blockers / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013116:Spinal Cord / Q000166:cytology*; D018709:Statistics, Nonparametric; D019789:Tetraethylammonium / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D050599:Vesicular Glutamate Transport Protein 2 / Q000378:metabolism; D020866:omega-Conotoxin GVIA / Q000494:pharmacology
chemical_list: D000596:Amino Acids; D002121:Calcium Channel Blockers; D002614:Chelating Agents; D018691:Excitatory Amino Acid Antagonists; D026902:Potassium Channel Blockers; C493475:Slc17a6 protein, rat; D026941:Sodium Channel Blockers; D050599:Vesicular Glutamate Transport Protein 2; C098463:dolaisoleucine; D049452:Green Fluorescent Proteins; D018698:Glutamic Acid; D013779:Tetrodotoxin; D004533:Egtazic Acid; D005439:Flufenamic Acid; D019789:Tetraethylammonium; D020866:omega-Conotoxin GVIA; D005968:Glutamate Decarboxylase; C013411:biocytin; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D008239:Lysine; D002118:Calcium