The Effect of Guanethidine and Local Anesthetics on the Electrically Stimulated Mouse Vas Deferens

• Published in: Anesthesia and analgesia Vol. 95; no. 5; pp. 1339 - 1343
• Main Authors: Joyce, Philip I, Rizzi, Daniela, Caló, Girolamo, Rowbotham, David J, Lambert, David G
• Format: Journal Article
• Language: English
• Published: United States International Anesthesia Research Society 01.11.2002
• Subjects: Adrenergic Agents - pharmacology; Adrenergic alpha-Antagonists - pharmacology; Anesthetics, Local - pharmacology; Animals; Cocaine - pharmacology; Electric Stimulation; Guanethidine - pharmacology; In Vitro Techniques; Male; Mice; Muscle Contraction - drug effects; Muscle, Smooth - drug effects; Prazosin - pharmacology; Prilocaine - pharmacology; Procaine - pharmacology; Tetrodotoxin - pharmacology; Vas Deferens - drug effects
• ISSN: 0003-2999; 1526-7598
• DOI: 10.1097/00000539-200211000-00045

Complex regional pain syndrome is often treated with the sympatholytic guanethidine and a local anesthetic in a Bier’s block. The efficacy of this treatment has been questioned. Because local anesthetics inhibit the norepinephrine uptake transporter, we hypothesized that this variable efficacy results from the local inhibiting the uptake of guanethidine. In this study, we tested this hypothesis by using a sympathetically innervated mouse vas deferens preparation. Organ bath-mounted mouse vasa deferentia were electrically stimulated in the absence and presence of guanethidine, prilocaine, procaine, and cocaine in various combinations. Prilocaine (1 mM) induced an immediate inhibition of twitch response (maximum 100% after 2 min) that fully reversed after washing. Guanethidine (3 μM) also inhibited twitching by 95% ± 3% in 15 min, but this effect was only partially reversed after 1 h of washing (33% ± 12% of control). When prilocaine and guanethidine were added in combination, a reversal of 80% ± 13% (at 1 h) was observed. Procaine (300 μM) produced a transient increase (152% ± 14%) in response. When co-incubated with guanethidine (3 μM), the twitch was reduced to 24% ± 4% of control and was reversed to 77% ± 7% after 1 h. Cocaine (30 μM) inhibited the twitch response to 53% ± 8%, which was fully reversed by 1 h of washing. When co-incubated with guanethidine, the response was reduced to 39% ± 6% of control and was reversed to 86% ± 10% after 1 h. In all cases, the reversal produced by the combination was significantly more intense (P < 0.05) than that produced by guanethidine alone. Local anesthetics reduce the sympatholytic actions of guanethidine, and this may explain the variable efficacy of guanethidine in the treatment of complex regional pain syndrome.