A postnatal switch in GABAergic control of spinal cutaneous reflexes.
GABAergic signalling exerts powerful inhibitory control over spinal tactile and nociceptive processing, but during development GABA can be depolarizing and the functional consequences of this upon neonatal pain processing is unknown. Here we show a postnatal switch in tonic GABA(A) receptor (GABA(A)R) modulation of cutaneous tactile and nociceptive reflexes from excitation to inhibition, but only in the intact spinal cord. Neonatal and 21-day-old (P21) rats were intrathecally treated with one of the GABA(A)R antagonists bicuculline and gabazine, with both compounds dose-dependently decreasing hindpaw mechanical and thermal withdrawal thresholds in P21 rats but increasing them in P3 neonates. Intrathecal gabazine also produced an increase in the cutaneous evoked electromyography (EMG) response of the biceps femoris in P21 rates but lowering the response in neonates. Injections of 3H-gabazine in the L4-L5 region at P3 confirmed that gabazine binding was restricted to the lumbar spinal cord. Spinalization of P3 neonates at the upper thoracic level prior to drug application reversed the behavioural and EMG responses to GABA antagonists so that they resembled those of P21 rats. The effects of spinalization were consistent with gabazine facilitation of ventral root potentials observed in isolated neonatal spinal cord. These data show a marked postnatal developmental switch in GABAergic control of neonatal nociception that is mediated by supraspinal structures and illustrate the importance of studying developmental circuits in the intact nervous system.
Hathway
Gareth
G
Department of Anatomy and Developmental Biology, University College London, Gower Street, London WC1E 6BT, UK. g.hathway@ucl.ac.uk
Harrop
Emily
E
Baccei
Mark
M
Walker
Suellen
S
Moss
Andrew
A
Fitzgerald
Maria
M
D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal; D004576:Electromyography / Q000379:methods; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D018756:GABA Antagonists / Q000493:pharmacokinetics / Q000494:pharmacology; D066298:In Vitro Techniques; D007796:Laminectomy / Q000379:methods; D009433:Neural Inhibition; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology*; D010147:Pain Measurement / Q000379:methods; D010812:Physical Stimulation / Q000379:methods; D011724:Pyridazines / Q000493:pharmacokinetics / Q000494:pharmacology; D051381:Rats; D012018:Reflex / Q000187:drug effects / Q000502:physiology*; D012684:Sensory Thresholds / Q000502:physiology; D012867:Skin / Q000294:innervation; D013116:Spinal Cord / Q000187:drug effects / Q000254:growth & development / Q000502:physiology*; D013126:Spinal Nerve Roots / Q000502:physiology; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D018756:GABA Antagonists; D011724:Pyridazines; D005680:gamma-Aminobutyric Acid; C049853:gabazine