Hypothalamospinal oxytocinergic antinociception is mediated by GABAergic and opiate neurons that reduce A-delta and C fiber primary afferent excitation of spinal cord cells.
Recent results implicate a new original mechanism involving oxytocin (OT), as a mediator via descending fibers of the paraventricular hypothalamic nucleus (PVN), in antinociception and analgesia. In rats electrical stimulation of the PVN or topical application of OT selectively inhibits A-delta and C fiber responses in superficial dorsal horn neurons, and this inhibition is reversed by a selective OT antagonist. However, little is known about the mechanisms and the spinal elements participating in this phenomenon. Here we show that topical application of bicuculline blocks the effects produced by PVN electrical stimulation or OT application. PVN electrical stimulation also activates a subpopulation of neurons in lamina II. These PVN-On cells are responsible for the amplification of local GABAergic inhibition. This result reinforces the suggestion that a supraspinal descending control of pain processing uses a specific neuronal pathway in the spinal cord in order to produce antinociception involving a GABAergic interneuron. Moreover, the topical administration of naloxone or a mu-opiate receptor antagonist beta-funaltrexamine only partially blocks the inhibitory effects produced by OT application or PVN electrical stimulation. Thus, this OT mechanism only involves opiate participation to a minor extent. The OT-specific, endogenous descending pathway represents an interesting mechanism to resolve chronic pain problems in special the neuropathic pain.
Condés-Lara
Miguel
M
Instituto de Neurobiología, Universidad Nacional Autónoma de México, Campus UNAM-Juriquilla, Querétaro 76230, Mexico. Condes@servidor.unam.mx
Rojas-Piloni
Gerardo
G
Martínez-Lorenzana
Guadalupe
G
López-Hidalgo
Mónica
M
Rodríguez-Jiménez
Javier
J
D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D004525:Efferent Pathways / Q000166:cytology / Q000378:metabolism; D004558:Electric Stimulation; D018756:GABA Antagonists / Q000494:pharmacology; D007031:Hypothalamus / Q000166:cytology / Q000378:metabolism*; D009292:Narcotic Antagonists / Q000494:pharmacology; D009413:Nerve Fibers, Myelinated / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D036421:Nerve Fibers, Unmyelinated / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D009619:Nociceptors / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018847:Opioid Peptides / Q000378:metabolism; D010121:Oxytocin / Q000378:metabolism* / Q000494:pharmacology; D010146:Pain / Q000378:metabolism / Q000503:physiopathology; D020671:Posterior Horn Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D013126:Spinal Nerve Roots / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D018756:GABA Antagonists; D009292:Narcotic Antagonists; D018847:Opioid Peptides; D010121:Oxytocin; D005680:gamma-Aminobutyric Acid; D001640:Bicuculline