Release of glutamate, nitric oxide and prostaglandin E2 and metabolic activity in the spinal cord of rats following peripheral nociceptive stimulation.
Peripheral tissue injury and inflammation may result in a facilitated spinal nociceptive transmission and central sensitization. Particularly, nitric oxide (NO) and prostaglandins (PGs) have been shown to be key mediators involved in the induction and maintenance of this state. By means of spinal cord microdialysis we have determined interstitial glutamate, NO (NO2-/NO3-), PGE2, glycerol, glucose and lactate concentrations in the dorsal horns of the spinal cord following peripheral nociceptive stimulation to gain further insight into the link between excitatory neurotransmitters and metabolic functions in the spinal cord during nociception. Formalin and zymosan injection into one hind paw evoked a biphasic release of glutamate and NO with the glutamate peaks preceding those of NO. Moreover, zymosan induced a biphasic increase of interstitial glycerol concentrations accompanied by an increase of interstitial lactate indicating metabolic disturbances. In contrast, formalin injection led to an elevation of dialysate glucose concentrations which may be interpreted as an indication of enhanced metabolic activity. The sequential release of glutamate and NO in the dorsal horns of the spinal cord in response to peripheral nociceptive stimulation supports the theory that NO may act as a retrograde transmitter. The metabolic changes observed after formalin and zymosan injection suggest that an intense peripheral nociceptive stimulation may not only activate but also disturb metabolic activity and possibly membrane integrity in the spinal cord.
Vetter
G
G
Pharmazentrum Frankfurt, Klinikum der Johann Wolfgang Goethe-Universität, Theodor-Stern-Kai 7, 60590, Frankfurt am Main, Germany.
Geisslinger
G
G
Tegeder
I
I
D000818:Animals; D015232:Dinoprostone / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism*; D005990:Glycerol / Q000378:metabolism; D019344:Lactic Acid / Q000378:metabolism; D008297:Male; D017551:Microdialysis; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D009573:Nitrites / Q000378:metabolism; D009619:Nociceptors / Q000378:metabolism*; D010146:Pain / Q000139:chemically induced / Q000378:metabolism; D010147:Pain Measurement; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000378:metabolism*; D015054:Zymosan
D009566:Nitrates; D009573:Nitrites; D009569:Nitric Oxide; D019344:Lactic Acid; D018698:Glutamic Acid; D015054:Zymosan; D015232:Dinoprostone; D005990:Glycerol