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

Abstract

AbstractInhibitory 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., 1993]. This inhibition is evoked by activation of Pacinian corpuscle afferents and is mediated in the spinal cord by adenosine acting through P1‐purinergic receptors. The adenosine‐mediated inhibition of nociceptive neurones by vibration is the result of an inhibitory postsynaptic potential (IPSP) produced by activating a K+ conductance. Adenosine is known to activate K+ currents in a number of different types of cell [Greene and Haas, 1985; Proctor and Dunwiddie, 1987; Segal, 1982; Trussell and Jackson, 1987; Gerber et al. 1989] and it has been reported that in cardiac muscle cells the + channels [Kirsch et al., 1990]. 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 [Ashcroft, 1988; Schmid Antomarchi et al., 1987a,b]. In addition, the IPSP evoked by vibratory stimulation was blocked by direct intracellular injection of AYP. 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 [Bini et al., 1984; Lundeberg, 1984; Lundeberg et al., 1984; Ottoson et al., 1981], We suggest that activation of ATP‐sensitive K+ channels ion 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. © 1993 Wiley‐Liss, Inc.