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Effect of Systemic Adenosine on Pain and Secondary Hyperalgesia Associated With the Heat/Capsaicin Sensitization Model in Healthy Volunteers
  1. Jesper Dirks, M.D.,
  2. Karin L. Petersen, M.D.,
  3. Michael C. Rowbotham, M.D. and
  4. Jørgen B. Dahl, M.D., Ph.D.
  1. From the Laboratory of Pain Physiology (J.D., J.B.D.), Department of Anaesthesiology, Herlev Hospital, Denmark; UCSF Pain Clinical Research Center, Departments of Neurology (K.L.P., M.C.R.) and Anesthesia (M.C.R.), University of California, San Francisco.
  1. Reprint requests: Jesper Dirks, M.D., Department of Anaesthesiology, Herlev University Hospital, DK-2730 Herlev, Denmark. E-mail: jedi{at}


Background and Objectives Adenosine is an endogenous compound that may have analgesic effects. Results from clinical trials are not consistent, however, and there is a need for large-scale, randomized, placebocontrolled studies to clarify the role of adenosine in the treatment of pain states, including acute nociceptive pain and pain involving central sensitization.

Methods The analgesic and antihyperalgesic effect of systemic adenosine on the heat/capsaicin sensitization model of experimental pain was investigated in 25 healthy human volunteers. Sensitization was produced by heating the skin to 45°C for 5 minutes, followed by a 30-minute application of 0.075% capsaicin cream, and maintained by periodically reheating the sensitized skin to 40°C for 5 minutes at 40-minute intervals. Subjects received intravenous adenosine 60 μg/kg/min or saline for 85 minutes. Areas of secondary hyperalgesia to von Frey hair and brush stimulation, heat-pain detection thresholds (HPDTs) in normal and sensitized skin, and painfulness of stimulation with 45°C for 1 minute (LTS) in normal skin were quantified before, during, and after study drug infusion.

Results Systemic adenosine had no effect on the area of secondary hyperalgesia to von Frey hair or brush stimulation, HPDT in normal or sensitized skin, or painfulness of LTS in normal skin.

Conclusion We conclude that adenosine has no effect on acute nociceptive pain induced by heat stimulation or on secondary hyperalgesia induced by heat/capsaicin sensitization in healthy volunteers.

  • Adenosine
  • Allodynia
  • Central sensitization
  • Hyperalgesia
  • Pain

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  • Supported by Danish Medical Research Council (Reg. No. 28809) and Novo Nordisk Foundation. K.L.P. is supported by the VZV Foundation, Inc. M.C.R. is supported by NIH Grant K24 NS02164.

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