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REGIONAL ANESTHESIA AND PAIN MANAGEMENT

Adenosine Reduces Secondary Hyperalgesia in Two Human Models of Cutaneous Inflammatory Pain

Karl-Fredrik Sjölund, MD, PhD^*, Märta Segerdahl, MD, PhD, and Alf Sollevi, MD, PhD

Karolinska Institute, Departments of Anesthesiology and Intensive Care, *Carolinska Hospital and Huddinge Hospital, Stockholm, Sweden

Address correspondence and reprint requests to Karl-Fredrik Sjölund, Department of Anesthesiology and Intensive Care, Karolinska Hospital, S-171 76 Stockholm, Sweden.

Secondary hyperalgesia is characterized by increased sensitivity to noxious mechanical stimuli in the area surrounding injured skin. The pathophysiological mechanisms involve increased excitability of second-order neurons located in the spinal cord, i.e., central sensitization. The mechanisms behind this phenomenon may be of importance in clinical pain, including neuropathic pain. To study the effects of systemic infusion of the endogenous compound adenosine (ADO) on sensory function, a superficial cutaneous burn injury was induced by the 4-min topical application of mustard oil or by heat (47°C for 7 min) during IV ADO infusion (60 µg · kg^-1 · min^-1). Healthy human subjects (n = 10 for each model) were tested, using a blinded, placebo-controlled procedure. The area of secondary hyperalgesia, as well as tactile and thermal sensory function, was tested using psychophysical methods during and after treatments. ADO significantly reduced the area of secondary hyperalgesia in both models. The maximal reduction compared with placebo was 58% ± 20% (heat burn) and 39% ± 13% (mustard oil burn). No other differences in sensory function were observed. The results are interpreted as an ADO-induced modulatory effect on the mechanisms of central sensitization.

Implications: We tested the effects of adenosine on the development of increased sensitivity in the skin surrounding a superficial skin injury in humans. A superficial skin burn was induced with a chemical irritant or heat. The results show that adenosine reduces the skin area with increased sensitivity surrounding the injury.

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