Algogen-specific pain processing in mouse spinal cord:: differential involvement voltage-dependent Ca2+ channels in synaptic transmission

1 The effects of intrathecal (i.t.) administration of N-, P/Q- or L-type voltage-dependent Ca2+-channel blockers were tested in two pain models involving bradykinin (BK)- and alpha,beta-methlene ATP (alpha,betameATP)-induced activation of primary afferent neurons in mice. 2 The nociceptive response (amount of time spent licking and biting the hindpaw) induced by intraplantar injection of BK (500 pmol mouse(-1)) was significantly attenuated by both w-conotoxin GVIA (N-type block-er) and calciseptine (L-type) but not by w-agatoxin IVA (P/Q-type). 3 The nociceptive response induced in a similar way by alpha,betameATP (100 nmol) was significantly inhibited by both the above N- and P/Q-type Ca2+-channel blockers but not by the L-type blocker. 4 The nociceptive responses elicited by BK and :, meATP were close-dependently inhibited by a tachykinin-NK l-receptor antagonist (L-703,606) and an N-methyl-(D)-aspartate (NMDA)-receptor antagonist (D-AP5). respectively. 5 Intrathecal administration of substance P (SP) (1.8 nmol) or NMDA (350 pmol) elicited algesic responses, such as licking. biting and scratching of the hindquarters. The SP-induced algesic behaviour was significantly inhibited by the L-type blocker but not by the N-type, The NMDA-induced response was not affected by either the N- or the P/Q-type block-er. 6 These findings suggest that BK and ATP most likely excite different types of sensory neurons in the periphery and that within the spinal cord the former stimulates peptidergic transmission regulated by presynaptic N- and postsynaptic L-type Ca2+ channels, while the latter stimulates glutamatergic transmission regulated by presynaptic N- and P/Q-type channels.