Inflammation reduces the contribution of N-type calcium channels to primary afferent synaptic transmission onto NK1 receptor-positive lamina I neurons in the rat dorsal horn.
N-type calcium channels contribute to the release of glutamate from primary afferent terminals synapsing onto nocisponsive neurons in the dorsal horn of the spinal cord, but little is known of functional adaptations to these channels in persistent pain states. Subtype-selective conotoxins and other drugs were used to determine the role of different calcium channel types in a rat model of inflammatory pain. Electrically evoked primary afferent synapses onto lumber dorsal horn neurons were examined three days after induction of inflammation with intraplantar complete Freund's adjuvant. The maximal inhibitory effect of the N-type calcium channel blockers, omega-conotoxins CVID and MVIIA, were attenuated in NK1 receptor-positive lamina I neurons after inflammation, but the potency of CVID was unchanged. This was associated with reduced inhibition of the frequency of asynchronous-evoked synaptic events by CVID studied in the presence of extracellular strontium, suggesting reduced N-type channel contribution to primary afferent synapses after inflammation. After application of CVID, the relative contributions of P/Q and L channels to primary afferent transmission and the residual current were unchanged by inflammation, suggesting the adaptation was specific to N-type channels. Blocking T-type channels did not affect synaptic amplitude under control or inflamed conditions. Reduction of N-type channel contribution to primary afferent transmission was selective for NK1 receptor-positive neurons identified by post hoc immunohistochemistry and did not occur at synapses in laminae II(o) or II(i), or inhibitory synapses. These results suggest that inflammation selectively downregulates N-type channels in the terminals of primary afferents synapsing onto (presumed) nociceptive lamina I NK1 receptor-positive neurons.
Rycroft
Beth K
BK
Pain Management Research Institute, Kolling Institute, University of Sydney at Royal North Shore Hospital, St Leonards 2065, Australia.
Vikman
Kristina S
KS
Christie
MacDonald J
MJ
D000344:Afferent Pathways / Q000503:physiopathology; D000818:Animals; D020864:Calcium Channels, N-Type / Q000187:drug effects / Q000378:metabolism*; D002908:Chronic Disease; D015536:Down-Regulation; D004558:Electric Stimulation; D005071:Evoked Potentials / Q000187:drug effects; D005260:Female; D005620:Freund's Adjuvant; D006614:Hindlimb; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D009619:Nociceptors; D010146:Pain / Q000378:metabolism / Q000503:physiopathology; D020671:Posterior Horn Cells / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018040:Receptors, Neurokinin-1 / Q000378:metabolism*; D013116:Spinal Cord / Q000503:physiopathology; D013569:Synapses; D009435:Synaptic Transmission; D014688:Venoms / Q000494:pharmacology; D020960:omega-Conotoxins
C461486:AM336; D020864:Calcium Channels, N-Type; D018040:Receptors, Neurokinin-1; D014688:Venoms; D020960:omega-Conotoxins; D005620:Freund's Adjuvant