Algogen‐specific pain processing in mouse spinal cord: differential involvement of voltage‐dependent Ca 2+ channels in synaptic transmission

The effects of intrathecal (i.t.) administration of N‐, P/Q‐ or L‐type voltage‐dependent Ca 2+ ‐channel blockers were tested in two pain models involving bradykinin (BK)‐ and α,β‐methylene ATP (α,βmeATP)‐induced activation of primary afferent neurons in mice. 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 ω‐conotoxin GVIA (N‐type blocker) and calciseptine (L‐type) but not by ω‐agatoxin IVA (P/Q‐type). The nociceptive response induced in a similar way by α,βmeATP (100 nmol) was significantly inhibited by both the above N‐ and P/Q‐type Ca 2+ ‐channel blockers but not by the L‐type blocker. The nociceptive responses elicited by BK and α,βmeATP were dose‐dependently inhibited by a tachykinin‐NK1‐receptor antagonist (L‐703,606) and an N‐methyl‐ D ‐aspartate (NMDA)‐receptor antagonist (D‐AP5), respectively. 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 blocker. 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 Ca 2+ channels, while the latter stimulates glutamatergic transmission regulated by presynaptic N‐ and P/Q‐type channels.British Journal of Pharmacology (2002) 135 , 1336–1342; doi: 10.1038/sj.bjp.0704578