Effects of adrenergic agonists and antagonists on tetrodotoxin-induced nerve block

Background and Objectives: The relative contributions of alpha (1)-, alpha (2)-, and beta -adrenergic receptors to adrenergic agonists' prolongation o f nerve block by tetrodotoxin (TTX) are unknown. We investigated which rece ptor agonists prolong TTX block, and whether delayed injection of antagonis ts can interrupt prolonged blocks after coinjection of TTX and agonists. Methods: Rats received percutaneous sciatic nerve block with 120 mu mol/L T TX with and without adrenergic agonists and antagonists. Block duration was assessed by a modified hot-plate test. Functional deficits in the uninject ed leg were used to assess systemic distribution of TTX. Data were expresse d as medians with 25th and 75th percentiles. Results: Coinjection of 5.5 mu mol/L phenylephrine (al-specific). 10 mu mol /L clonidine (alpha (2)-specific), and 1.1 mu mol/L epinephrine (mixed alph a- and beta -agonist) prolonged TTX nerve block, but 5.5 mu mol/L isoproter enol (mixed P-agonist) did not. Yohimbine inhibited TTX block prolongation by clonidine (median inhibitory concentrations, IC50 = 130 nmol/L); phentol amine similarly inhibited epinephrine (IC50 = 45 nmol/L). Adrenergic antago nists did not inhibit the prolongation of TTX block by agonists when inject ed 3 or 6 hours after the initial block. Subcutaneous injection of adrenerg ic agonists at a remote site did not prolong TTX block, except for a modest prolongation by clonidine. Conclusions: TTX block can be prolonged by alpha (1)- and alpha (2)-, but n ot beta -adrenergic agonists via locally mediated events of relatively brie f duration. Delayed injection of adrenergic antagonists does not interrupt the prolonged blocks produced by coinjection of TTX and adrenergic agonists unless administered soon after block is established.