Preliminary Pharmacological Research Of Co-application Low Concentration Bupivacaine With QX-314-OH On Nerve Blockade

Objective: The N-ethylated derivative of lidocaine, QX-314 is permanently charged and thus dose not permeate the membrane passively. Study rencently, QX-314 permeated through TRPV1 channel activated by bupivacine, accumulated intracellularly after activation of this channel. Upon sciatic injections, bupivacaine markedly prolonged QX-314’s nociceptive block and also extended（to a lesser degree） its motor block. QX-314-OH is the hydroxide compound of QX-314, QX-314-OH’s nociceptive blockage EC₅₀ and motor blockage EC₅₀ would be calculated through the rats sciatic nerve block model. Co-administrate different concentrations QX-314-OH with 0.0375% bupivacaine, we hypothesized that 0.0375% bupicacine would enhance the QX-314-OH nerve blockage, prolong the duration,and without nerve toxicity.Methods: 10,15,20,25,30,40,80 m M QX-314-OH were administrated through the rats sciatic nerve block model, QX-314-OH’s nociceptive blockage EC₅₀ and motor blockage EC₅₀ would be calculated with the BLISS method.Co-inject different concentrations QX-314-OH with 0.0375% bupivacaine,abservated the nerve blockage’s efficacy, the onset time and the block duration. Animals were euthanized at 1,3,7,15 days after drug administration and sciatic nerves harvested for histological analysis.Result:1. QX-314-OH’s nociceptive blockage EC₅₀ was 10 m M and motor blockage EC₅₀ was 10 m M in the rats sciatic nerve block model. Feeling（tactile, pin prick） and motor block EC₅₀, respectively（13 m M, 19 m M） and 27 m M.2. 0.0375% bupivacaine markedly hance QX-314-OH nerve blockage effective, prolong the nerve blockage duration with QX-314-OH’ concentration dependent.3. 10、15 m M QX-314-OH administrated with 0.0375% bupivacaine, nociceptive block duration was longer than motor block.4. Observation by light microscope: No obvious nerve injure in any group, but at the 1 day, groups had varying degrees inflammatory cell infiltration in the sciatic. In particular at 25 m M QX-314-OH with or without 0.0375% bupivacaine had severity inflammatory cell infiltration, fortunately no inflammatory cell infiltration at the 3,7,15 d.Conclusion:1. 0.0375% bupivacaine markedly hance QX-314-OH nerve blockage and prolong the duration. 0.0375%bupivacaine markedly prolonged QX-314-OH’s nociceptive block than its motor block in some concentration.2. QX-314-OH administrated with 0.0375% bupivacaine can produce transient reversible inflammatory cell infiltration but no nerve injury to the sciatic nerve.