Inflammatory pain upregulates spinal inhibition via endogenous neurosteroid production.
Inhibitory synaptic transmission in the dorsal horn (DH) of the spinal cord plays an important role in the modulation of nociceptive messages because pharmacological blockade of spinal GABAA receptors leads to thermal and mechanical pain symptoms. Here, we show that during the development of thermal hyperalgesia and mechanical allodynia associated with inflammatory pain, synaptic inhibition mediated by GABAA receptors in lamina II of the DH was in fact markedly increased. This phenomenon was accompanied by an upregulation of the endogenous production of 5alpha-reduced neurosteroids, which, at the spinal level, led to a prolongation of GABAA receptor-mediated synaptic currents and to the appearance of a mixed GABA/glycine cotransmission. This increased inhibition was correlated with a selective limitation of the inflammation-induced thermal hyperalgesia, whereas mechanical allodynia remained unaffected. Our results show that peripheral inflammation activates an endogenous neurosteroid-based antinociceptive control, which discriminates between thermal and mechanical hyperalgesia.
Poisbeau
Pierrick
P
Institut des Neurosciences Cellulaires et Intégratives, Centre National de la Recherche Scientifique/Université Louis Pasteur, F-67084 Strasbourg, France. poisbeau@neurochem.u-strasbg.fr
Patte-Mensah
Christine
C
Keller
Anne Florence
AF
Barrot
Michel
M
Breton
Jean-Didier
JD
Luis-Delgado
Oliva Erendira
OE
Freund-Mercier
Marie José
MJ
Mensah-Nyagan
Ayikoe Guy
AG
Schlichter
Rémy
R
D000818:Animals; D007249:Inflammation / Q000378:metabolism / Q000503:physiopathology; D009433:Neural Inhibition / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000096:biosynthesis*; D010146:Pain / Q000378:metabolism*; D010147:Pain Measurement / Q000379:methods; D051381:Rats; D017208:Rats, Wistar; D013116:Spinal Cord / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology; D015854:Up-Regulation / Q000502:physiology*
D018377:Neurotransmitter Agents