INTRATHECAL ADENOSINE ADMINISTRATION - A PHASE-1 CLINICAL SAFETY STUDY IN HEALTHY-VOLUNTEERS, WITH ADDITIONAL EVALUATION OF ITS INFLUENCE ON SENSORY THRESHOLDS AND EXPERIMENTAL PAIN

Background: Several animal studies show antinociceptive effects of int rathecally administered adenosine and its analogs. However, there is n o clinical experience regarding the effects of intrathecal adenosine i n humans. Methods: The side effects and analgesic effects of intrathec al adenosine (500-2,000 mu g) on experimental pain were studied in 12 healthy volunteers. Before and after adenosine was given, the authors evaluated the cold pain rating of the foot (submersion in ice water fo r 1 min), the forearm ischemic pain rating during a 30-min tourniquet: test, and the thermal and tactile pain thresholds on healthy and infl amed skin after application of mustard oil (4 min) to the calf. The ar eas of secondary allodynia surrounding the inflammation were also dete rmined The cerebrospinal fluid level of adenosine was determined befor e and after injection. Results: Intrathecal adenosine caused a 1,000- to 2,000-fold elevation of the cerebrospinal fluid concentration. One volunteer experienced, transient (30 min) lumbar pain after injection at a dose of 2,000 mu g. There mere no other complications in any othe r volunteers. Adenosine reduced, in a non-dose-dependent manner, the a reas of secondary allodynia after skin inflammation (brush, P < 0.06; and von Prey hair, P < 0.03) and reduced the forearm tourniquet ischem ic pain rating (P = 0.01). Tactile pain thresholds were significantly reduced by mustard oil inflammation during control, whereas adenosine treatment prevented this reduction. The ice water-induced cold pain ra ting was not influenced hy adenosine. Conclusions: An intrathecal aden osine injection of 1,000 mu g lacked side effects in healthy volunteer s. The compound attenuated different types of experimental pain.