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Subcutaneous injection of inhaled anesthetics produces cutaneous analgesia

[L’injection sous-cutanée d’agents anesthésiques volatils génère une analgésie cutanée]

Chin C. Chu, MD^*,, Su Z. Wu, MD^*, Wan L. Su, MS^*, Ja P. Shieh, MD MS^*, Cheng H. Kao, MD, Shung T. Ho, MD MS and Jhi J. Wang, MD PhD^*

^* From the Departments of Anesthesiology, and
Surgery, Chi-Mei Medical Center, Tainan; the
Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei; and the
Department of Anesthesiology, Tri-Service General Hospital, Taipei, Taiwan.

Address correspondence to: Dr. Jhi-Joung Wang, Department of Anesthesiology, Chi-Mei Medical Center, Tainan, Taiwan. Phone: 886-6-2517844; Fax: 886-6-2832639; E-mail: 400002{at}mail.chimei.org.tw

Purpose: Previous investigations suggest that inhaled anesthetics may produce cutaneous analgesia. The objective of this study was to evaluate whether inhaled anesthetics have a direct analgesic effect on skin.

Methods: We conducted subcutaneous injections of one of three inhaled anesthetics (halothane, isoflurane, and enflurane) or one of two local anesthetics (lidocaine and procaine) at various dosages in rats (n = 6 rats, for each dose of each drug). Subcutaneous injections of vehicles (saline or olive oil) were used as controls (n = 6 rats for each vehicle). We constructed concentration-response curves, wherein the concentrations of drugs tested in subcutaneous tissue fluid were estimated by calculation, and the cutaneous analgesic effects of drugs were evaluated by pinprick tests on skin.

Results: Like local anesthetics, subcutaneous injection of inhaled anesthetics produced concentration-dependent, cutaneous analgesia which attained maximum (complete cutaneous analgesia) at high concentration. This effect was reversible and localized in the area of injection. On the basis of 50% effective concentration, the ranking of potencies was lidocaine > halothane > isoflurane > enflurane > procaine (P < 0.05 for all differences). Subcutaneous injections of vehicles did not produce cutaneous analgesia.

Conclusions: Like local anesthetics (lidocaine and procaine), subcutaneous injections of inhaled anesthetics (halothane, isoflurane, and enflurane) produced a concentration-dependent, cutaneous, analgesic effect at the site of injection. Inhaled anesthetics have a direct analgesic effect on skin.

1 Campagna JA, Miller KW, Forman SA. Mechanisms of actions of inhaled anesthetics. N Engl J Med 2003; 348: 2110–24.[Free Full Text]

2 Evers AS, Crowder CM. General anesthetics. In: Hardman JG, Limbird LE (Eds). Goodman & Gilman’s the Pharmacological Basis of Therapeutics, 10^th ed. NY: The McGraw-Hill Companies; 2001: 337–65.

3 Hemmings HC Jr, Akabas MH, Goldstein PA, Trudell JR, Orser BA, Harrison NL. Emerging molecular mechanisms of general anesthetic action. Trends Pharmacol Sci 2005; 26: 503–10.[Medline]

4 Scholz A, Appel N, Vogel W. Two types of TTX-resistant and one TTX-sensitive Na+ channel in rat dorsal root ganglion neurons and their blockade by halothane. Eur J Neurosci 1998; 10: 2547–56.[Medline]

5 Fassoulaki A, Sarantopoulos C, Karabinis G, Derveniotis C. Skin application of isoflurane attenuates the responses to a mechanical and an electrical stimulation. Can J Anaesth 1998; 45: 1151–5.[Abstract/Free Full Text]

6 Grond S, Radbruch L, Lehmann KA. Clinical pharmacokinetics of transdermal opioids: focus on transdermal fentanyl. Clin Pharmacokinet 2000; 38: 59–89.[Medline]

7 Khan MA, Gerner P, Sudoh Y, Wang GK. Use of a charged lidocaine derivative, tonicaine, for prolonged infiltration anesthesia. Reg Anesth Pain Med 2002; 27: 173–9.[Medline]

8 Honemann CW, Washington J, Honemann MC, Nietgen GW, Durieux ME. Partition coefficients of volatile anesthetics in aqueous electrolyte solutions at various temperatures. Anesthesiology 1998; 89: 1032–5.[Medline]

9 Firestone LL, Mille, JG, Mille, KW. Tables of physical and pharmacological properties of anesthetics. In: Roth SH, Miller KW (Eds). Molecular and Cellular Mechanisms of Anesthetics. NY: Plenum Medical Book Company; 1986: 455–70.

10 Renzi F, Waud BE. Partition coefficients of volatile anesthetics in Kreb’ s solution. Anesthesiology 1977; 47: 62–3.[Medline]

11 Minkin S, Kundhal K. Likelihood-based experimental design for estimation of ED50. Biometrics 1999; 55: 1030–7.[Medline]

12 Fozzard HA, Lee PJ, Lipkind GM. Mechanism of local anesthetic drug action on voltage-gated sodium channels. Curr Pharm Des 2005; 11: 2671–86.[Medline]

13 Lipkind GM, Fozzard HA. Molecular modeling of local anesthetic drug binding by voltage-gated sodium channels. Mol Pharmacol 2005; 68: 1611–22.[Abstract/Free Full Text]

14 Ouyang W, Hemmings HC Jr. Depression by isoflurane of the action potential and underlying voltage-gated ion currents in isolated rat neurohypophysial nerve terminals. J Pharmacol Exp Ther 2005; 312: 801–8.[Abstract/Free Full Text]

15 Ouyang W, Wang G, Hemmings HC Jr. Isoflurane and propofol inhibit voltage-gated sodium channels in isolated rat neurohypophysial nerve terminals. Mol Pharmacol 2003; 64: 373–81.[Abstract/Free Full Text]

16 Rehberg B, Xiao YH, Duch DS. Central nervous system sodium channels are significantly suppressed at clinical concentrations of volatile anesthetics. Anesthesiology 1996; 84: 1223–33.[Medline]