title: Injection pain of rocuronium and vecuronium is evoked by direct activation of nociceptive nerve endings.
abstract: 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.
authors.affiliation: Friedrich-Alexander University, Department of Anaesthesiology, Erlangen, Germany.
authors.forename: J A
authors.initials: JA
authors.lastname: Blunk
authors.forename: F
authors.initials: F
authors.lastname: Seifert
authors.forename: M
authors.initials: M
authors.lastname: Schmelz
authors.forename: P W
authors.initials: PW
authors.lastname: Reeh
authors.forename: W
authors.initials: W
authors.lastname: Koppert
mesh_terms: D000328:Adult; D000732:Androstanols / Q000009:adverse effects*; D000818:Animals; D004558:Electric Stimulation; D004594:Electrophysiology; D005260:Female; D005542:Forearm / Q000098:blood supply; D006801:Humans; D066298:In Vitro Techniques; D017078:Laser-Doppler Flowmetry; D008297:Male; D051379:Mice; D017551:Microdialysis; D009411:Nerve Endings / Q000187:drug effects*; D009412:Nerve Fibers / Q000187:drug effects / Q000502:physiology; D009431:Neural Conduction / Q000187:drug effects; D003473:Neuromuscular Nondepolarizing Agents / Q000009:adverse effects*; D009619:Nociceptors / Q000187:drug effects*; D010146:Pain / Q000139:chemically induced*; D012039:Regional Blood Flow / Q000502:physiology; D000077123:Rocuronium; D014673:Vecuronium Bromide / Q000009:adverse effects*
chemical_list: D000732:Androstanols; D003473:Neuromuscular Nondepolarizing Agents; D014673:Vecuronium Bromide; D000077123:Rocuronium