High concentrations of adrenergic antagonists prolong sciatic nerve blockade by tetrodotoxin.
BACKGROUND
Millimolar-range concentrations of some adrenergic antagonists have been shown to have local anesthetic-like properties, and to stimulate GTPase activity in vitro. In this report, we investigate whether these agents can potentiate the effect of tetrodotoxin (TTX) and bupivacaine, a conventional local anesthetic, and whether GTPase activation plays a role.


METHODS
Rats received sciatic nerve blockade with tetrodotoxin or bupivacaine co-injected with adrenergic antagonists and/or agonists, or pertussis toxin. Thermal nociceptive blockade was quantified with modified hotplate testing.


RESULTS
Nerve block from TTX alone lasted 153 (99-223) min (median and 25th and 75th percentiles). Co-injection with 20 mM phentolamine, propranolol, and yohimbine prolonged TTX block to 856 (765-862), 486 (444-510), and 465 (413-495) min respectively (P<0.005 in all cases, compared to TTX alone). Micromolar concentrations of adrenergic antagonists (which inhibited the prolongation of TTX block by epinephrine) did not prolong TTX block. Injection of adrenergic antagonists alone did not produce specific nerve block. They did not prolong TTX block when injected at a remote subcutaneous site. Prolongation of TTX block by phentolamine was not inhibited by co-injection with pertussis toxin. Adrenergic antagonists did not prolong bupivacaine block.


CONCLUSIONS
High concentrations of adrenergic antagonists markedly prolonged TTX block, but not bupivacaine block. This locally mediated action does not appear to be adrenergic-receptor-specific, or mediated by GTPase activation.
Kohane
D S
DS
Department of Anesthesia, Children's Hospital, Boston, Massachusetts, USA.
Lu
N T
NT
Crosa
G A
GA
Kuang
Y
Y
Berde
C B
CB
D000322:Adrenergic Agonists / Q000494:pharmacology; D018674:Adrenergic Antagonists / Q000494:pharmacology*; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002045:Bupivacaine / Q000494:pharmacology; D007279:Injections, Subcutaneous; D008297:Male; D009407:Nerve Block; D037342:Pertussis Toxin; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000187:drug effects*; D013779:Tetrodotoxin / Q000494:pharmacology*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D000322:Adrenergic Agonists; D018674:Adrenergic Antagonists; D000779:Anesthetics, Local; D010566:Virulence Factors, Bordetella; D013779:Tetrodotoxin; D037342:Pertussis Toxin; D002045:Bupivacaine