An inhibitory postsynaptic potential in spinal nociceptive neurones is mediated by adenosine through activation of ATP-sensitive K+ channels

✍ Scribed by Michael W. Salter; Yves De Koninck; James L. Henry

• Publisher: John Wiley and Sons
• Year: 1993
• Tongue: English
• Weight: 682 KB
• Volume: 28
• Category: Article
• ISSN: 0272-4391
• DOI: 10.1002/ddr.430280342

✦ Synopsis

Inhibitory processes within the dorsal horn participate in regulating the transmission of nociceptive information. Spinal nociceptive neurones are inhibited by cutaneously applied vibration and we have characterized this inhibition physiologically and pharmacologically [Salter et al., 19931. This inhibition i s evoked by activation of Pacinian corpuscle afferents and is mediated in the spinal cord by adenosine acting through PI-purinergic receptors. The adenosine-mediated inhibition of nociceptive neurones by vibration is the result of an inhibitory postsynaptic potential (IPSP) produced by activating a Kt conductance. Adenosine is known to activate K + currents in a number of different types of cell [Greene and Haas, 1985; Gerber et al., 19891 and it has been reported that in cardiac muscle cells the K+ channels activated by adenosine are the so-called ATP-sensitive K+ channels [Kirsch et al., 19901. Therefore, we investigated the possibility that these channels might mediate the IPSP we have observed in nociceptive dorsal horn neurones upon vibratory stimulation applied to the skin. We found that the inhibition of nociceptive neurones by this stimulation is abolished by glibenclamide, a blocker of ATP-sensitive K+ channels Schmid Antomarchi et al., 1987a,b]. In addition, the IPSP evoked by vibratory stimulation was blocked by direct intracellular injection of ATP. These results suggest that the adenosine-mediated IPSP in nociceptive spinal neurones results from activating ATP-sensitive K+ channels in these neurones. As this inhibition of nociceptive dorsal horn neurones may be the physiological basis for the analgesia produced by vibratory stimulation in humans Ottoson et al., 19811, we suggest that activation of ATP-sensitive K + channels in nociceptive neurones may mediate this analgesia. A diversity of drugs exists which act on ATP-sensitive K+ channels and we further suggest that such drugs might be therapeutically useful in enhancing the analgesia produced by vibration or in producing analgesia on their own.