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Injection pain of rocuronium and vecuronium is evoked by direct activation of nociceptive nerve endings

Published online by Cambridge University Press:  02 June 2005

J. A. Blunk ,
F. Seifert ,
M. Schmelz ,
P. W. Reeh  and
W. Koppert
J. A. Blunk
Affiliation:
Friedrich-Alexander University, Department of Anaesthesiology, Erlangen, Germany
F. Seifert
Affiliation:
Friedrich-Alexander University, Department of Physiology and Experimental Pathophysiology, Erlangen, Germany
M. Schmelz
Affiliation:
Friedrich-Alexander University, Department of Physiology and Experimental Pathophysiology, Erlangen, Germany
P. W. Reeh
Affiliation:
Friedrich-Alexander University, Department of Physiology and Experimental Pathophysiology, Erlangen, Germany
W. Koppert
Affiliation:
Friedrich-Alexander University, Department of Anaesthesiology, Erlangen, Germany
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Extract

Summary

Background and objective: Rocuronium and, to a lesser extent, vecuronium can induce burning sensations associated with withdrawal reactions during administration. Dermal microdialysis in human and electrophysiological recordings of nociceptors in mouse skin were used to elucidate the underlying mechanisms of pain induction.

Methods: Microdialysis catheters were inserted intradermally into the forearm of 10 volunteers and were perfused with two different concentrations of rocuronium and vecuronium (1 and 10 mg mL−1) or a control. Dialysis samples were taken every 15 min and analysed for protein, histamine, tryptase and bradykinin content. Pain intensity was rated on a numerical scale of 0–10. In a parallel design, activation of cutaneous nociceptors was assessed directly in a skin–nerve in vitro preparation of the mouse hind paw. The receptive fields of identified single C-nociceptors (n = 12) were superfused with rocuronium or vecuronium solutions (10 mg mL−1) at physiological pH.

Results: In accordance with clinical observations, microdialysis of rocuronium (10 mg mL−1) induced sharp burning pain (NRS 4.1 ± 1.8), whereas vecuronium given in the usual clinical concentration (1 mg mL−1) induced only minor pain sensations (NRS 0.6 ± 1.3). At equimolar concentrations, pain sensation and concomitant mediator release evoked by both drugs were similar. No correlations were found between pain rating and mediator release. In the in vitro preparation, C-fibres showed a consistent excitatory response with rapid onset after stimulation with vecuronium as well as rocuronium (differences not significant).

Conclusions: The algogenic effect of aminosteroidal neuromuscular blocking drugs can be attributed to a direct activation of C-nociceptors.

Keywords

NEUROMUSCULAR-BLOCKING AGENTS, vecuronium bromide, rocuronium bromidePERIPHERAL NERVOUS SYSTEM, nociceptorsPSYCHOPHYSIOLOGY, pain
Type
Original Article
Information
European Journal of Anaesthesiology , Volume 20 , Issue 3 , March 2003 , pp. 245 - 253
Copyright
© 2003 European Society of Anaesthesiology

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References

Lockey D, Coleman P. Pain during injection of rocuronium bromide. Anaesthesia 1995; 50: 474.Google Scholar
Moorthy SS, Dierdorf SF. Pain on injection of rocuronium bromide. Anesth Analg 1995; 80: 1067.Google Scholar
Robertson EN. Pain on administration of vecuronium. Anaesthesia 1996; 51: 93.Google Scholar
Steeger MAH, Robertson EN. Pain on injection of rocuronium bromide. Anesth Analg 1996; 83: 203.Google Scholar
Joshi GP, Whitten CW. Pain on injection of rocuronium bromide. Anesth Analg 1997; 84: 228.Google Scholar
Borgeat A, Kwiatkowski D. Spontaneous movements associated with rocuronium: is pain on injection the cause? Br J Anaesth 1997; 79: 382–383.Google Scholar
Shevchenko Y, Jocson JC, McRae VA, et al. The use of lidocaine for preventing the withdrawal associated with the injection of rocuronium in children and adolescents. Anesth Analg 1999; 88: 746–748.Google Scholar
Robertson EN, Hull JM, Verbeek AM, Booij LHDJ. A comparison of rocuronium and vecuronium: the pharmacodynamic, cardiovascular and intra-ocular effects. Eur J Anaesthesiol 1994; 11: 116–121.Google Scholar
Kent AP, Bricker SRW, Coleman P. Pain during injection of vecuronium. Anaesthesia 1988; 43: 334.Google Scholar
Chow LH, Ho CM, Yang YC, Lee TY, Lui PW. Vecuronium dissolved in normal saline exaggerates pain on intravenous injection. Chung-Hua-I-Hsueh-Tsa-Chih-Taipei 1995; 55: 315–318.Google Scholar
Schmelz M, Luz O, Averbeck B, Bickel A. Plasma extravasation and neuropeptide in human skin as measured by intradermal microdialysis. Neurosci Lett 1997; 230: 1–4.Google Scholar
Lischetzki G, Rukwied R, Handwerker HO, Schmelz M. Nociceptor activation and protein extravasation induced by inflammatory mediators in human skin. Eur J Pain 2001; 5: 49–57.Google Scholar
Koltzenburg M, Handwerker HO. Differential ability of human cutaneous nociceptors to signal mechanical pain and to produce vasodilatation. J Neurosci 1994; 14: 1756–1765.Google Scholar
Petersen LJ, Poulsen LK, Sondergaard J, Skov PS. The use of cutaneous microdialysis to measure substance P-induced histamine release in intact human skin in vivo. J Allergy Clin Immunol 1994; 94: 773–783.Google Scholar
Reeh PW. Sensory receptors in mammalian skin in an in vitro preparation. Neurosci Lett 1986; 66: 141–146.Google Scholar
Bretag A. Synthetic interstitial fluid for isolated mammalian tissue. Life Sci 1969; 8: 319–329.Google Scholar
Forster C, Handwerker HO. Automatic classification and analysis of microneurographic spike data using a PC/AT. J Neurosci Methods 1990; 31: 109–118.Google Scholar
Cheong KF, Wong WH. Pain on injection of rocuronium: influence of two doses of lidocaine pre-treatment. Br J Anaesth 2000; 84: 106–107.Google Scholar
Arndt JO, Klement W. Pain evoked by polymodal stimulation of hand veins in humans. J Physiol 1991; 440: 467–478.Google Scholar
Klement W, Arndt JO. Pain on i.v. injection of some anaesthetic agents is evoked by the unphysiological osmolality or pH of their formulations. Br J Anaesth 1991; 66: 189–195.Google Scholar
Kindgen-Milles D, Klement W, Arndt JO. The nociceptive systems of skin, paravascular tissue and hand veins of humans and their sensitivity to bradykinin. Neurosci Lett 1994; 181: 39–42.Google Scholar
Schmelz M, Zeck S, Raithel M, Rukwied R. Mast cell tryptase in dermal neurogenic inflammation. Clin Exp Allergy 1999; 29: 652–659.Google Scholar
Steen KH, Reeh PW, Anton F, Handwerker HO. Protons selectively induce lasting excitation and sensitization to mechanical stimulation of nociceptors in rat skin, in vitro. J Neurosci 1992; 12: 86–95.Google Scholar
Koppert W, Blunk JA, Petersen LJ, Skov P, Rentsch K, Schmelz M. Different patterns of mast cell activation by muscle relaxants in human skin. Anesthesiology 2001; 95: 659–667.Google Scholar
Rukwied R, Lischetzki G, McGlone F, Heyer G, Schmelz M. Mast cell mediators other than histamine induce pruritus in atopic dermatitis patients: a dermal microdialysis study. Br J Dermatol 2000; 142: 1114–1120.Google Scholar
Kress M, Reeh PW. Chemical excitation and sensitization in nociceptors. In: Belmonte C, Cervero F, eds. Neurobiology of Nociceptors. Oxford, UK: University Press, 1996: 258–297.
Petersen LJ, Poulsen LK, Sondergaard J, Skov PS. The use of cutaneous microdialysis to measure substance P-induced histamine release in intact human skin in vivo. J Allergy Clin Immunol 1994; 94: 773783.Google Scholar
Kress M, Guthmann C, Averbeck B, Reeh PW. Calcitonin-gene related peptide and prostaglandin E2 but not Substance P release induced by antidromic nerve stimulation from rat skin, in vitro. Neuroscience 1999; 89: 303–310.Google Scholar
Bernardini N, Sauer SK, Haberberger R, Fischer MJ, Reeh PW. Excitatory nicotinic and desensitizing muscarinic (M2) effects on C-nociceptors in isolated rat skin. J Neurosci 2001; 21: 3295–3202.Google Scholar
Liang YF, Haake B, Reeh PW. Sustained sensitisation and recruitment of rat cutaneous nociceptors by bradykinin and a novel theory of its excitatory action. J Physiol 2001; 532: 229–239.Google Scholar