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PAIN MEDICINE

The Effect of Intravenous Infusion of Adenosine on Electrically Evoked Hyperalgesia in a Healthy Volunteer Model of Central Sensitization

Boris A. Chizh, MD PhD^*, Martin Dusch, Martin Puthawala, Martin Schmelz, MD PhD, Louise M. Cookson^*, Reynaldo Martina, John Brown, MD^*, and Wolfgang Koppert, MD

*Translational Medicine and Statistics, GlaxoSmithKline, Cambridge, United Kingdom; and Department of Physiology, University of Erlangen, Erlangen, Germany

Address correspondence and reprint requests to Boris A. Chizh, MD, PhD, GlaxoSmithKline, Addenbrooke’s Centre for Clinical Investigation, Hills Rd., Cambridge CB2 2GG, UK. Address e-mail to Boris_A_Chizh{at}gsk.com

Human pain models invoking central sensitization, one of the key mechanisms of chronic pain, may be useful for characterizing new analgesics. A new model of electrical hyperalgesia can detect the efficacy of several analgesic mechanisms. Because IV adenosine can alleviate neuropathic pain, we investigated its effect on experimental sensitization. This was a double-blinded, randomized, two-period crossover study in 20 healthy volunteers. Current pulses (0.5 ms; 1 Hz) were applied intracutaneously to achieve pain rating of 5 on a 0–10 numeric rating scale. Pain, areas of pinprick hyperalgesia, and tactile allodynia were assessed during the 2.5-h stimulation period. Adenosine (50 µg · kg^–1 · min^–1) and placebo were infused IV over 60 min. Additional testing was performed 24 h after each treatment. Adenosine reduced the area of pinprick hyperalgesia during the infusion compared with placebo; there was no significant effect on tactile allodynia or pain rating. The effect on hyperalgesia developed over 15 min and was significant (P 0.05) for the rest of the infusion period. There was no difference between treatments at 24 h. Thus, in accordance with reports on neuropathic pain, adenosine reduced central sensitization in the human model of electrical hyperalgesia. However, adenosine did not have the long-term effects seen in patients. The model can investigate mechanisms of drugs for the treatment of chronic pain.

IMPLICATIONS: A controlled study of IV adenosine in a healthy volunteer model of electrically evoked hyperalgesia demonstrated a reduction of measures of central sensitization, a key mechanism of neuropathic pain. Because adenosine can alleviate neuropathic pain in patients, the model may be useful for early characterization of new treatments for this indication in humans.

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