Intrathecal Adenosine Administration: A Phase 1 Clinical Safety Study in Healthy Volunteers, with Additional Evaluation of Its Influence on Sensory Thresholds and Experimental Pain

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Abstract

Background

Several animal studies show antinociceptive effects of intrathecally administered adenosine and its analogs. However, there is no clinical experience regarding the effects of intrathecal adenosine in humans.

Methods

The side effects and analgesic effects of intrathecal adenosine (500-2,000 [micro sign]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 for 1 min), the forearm ischemic pain rating during a 30-min tourniquet test, and the thermal and tactile pain thresholds on healthy and inflamed skin after application of mustard oil (4 min) to the calf. The areas of secondary allodynia surrounding the inflammation were also determined. The cerebrospinal fluid level of adenosine was determined before 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 [micro sign]g. There were no other complications in any other volunteers. Adenosine reduced, in a non-dose-dependent manner, the areas of secondary allodynia after skin inflammation (brush, P < 0.06; and von Frey hair, P < 0.03) and reduced the forearm tourniquet ischemic 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 rating was not influenced by adenosine.

Conclusions

An intrathecal adenosine injection of 1,000 [micro sign]g lacked side effects in healthy volunteers. The compound attenuated different types of experimental pain.

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