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 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 microg) 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 microg. 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 microg lacked side effects in healthy volunteers. The compound attenuated different types of experimental pain.
Rane
K
K
Department of Anesthesia, Danderyds Hospital, Stockholm, Sweden.
Segerdahl
M
M
Goiny
M
M
Sollevi
A
A
D000241:Adenosine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000293:Adolescent; D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D002317:Cardiovascular Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003872:Dermatitis / Q000503:physiopathology; D005260:Female; D006207:Half-Life; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007101:Immersion; D007278:Injections, Spinal; D007511:Ischemia / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010147:Pain Measurement / Q000187:drug effects*; D012684:Sensory Thresholds / Q000187:drug effects*
D002317:Cardiovascular Agents; D000241:Adenosine