Dose response of intrathecal adenosine in experimental pain and allodynia.
BACKGROUND
Intrathecal adenosine reduces areas of mechanical hypersensitivity and provides analgesia in patients with neuropathic pain. Adenosine also causes side effects, yet its dose response for either efficacy or side effects has not been examined in double blind studies. We studied two doses of intrathecal adenosine in humans with experimental hypersensitivity and the ability of the adenosine receptor antagonist, aminophylline, to reverse adenosine's effects.


METHODS
Following Internal Review Board approval and written informed consent, 35 volunteers were studied. Five volunteers were studied to confirm the stability of a new method of inducing hypersensitivity with capsaicin. The remaining 30 volunteers received, in a randomized, double-blind manner, saline, or adenosine, 0.5 or 2.0 mg, by intrathecal injection 40 min after areas of allodynia and hyperalgesia were established from capsaicin. Two hr later, volunteers were randomized to receive intravenous saline or aminophylline, 5 mg/kg.


RESULTS
Topical capsaicin with intermittent heating resulted in stable areas of allodynia and hyperalgesia. Intrathecal adenosine, but not saline, reduced areas of allodynia and hyperalgesia from capsaicin, with no differences between doses. Side effects occurred in 1, 2, and 6 volunteers receiving saline, 0.5 mg and 2.0 mg adenosine, respectively. Aminophylline failed to reverse adenosine's effects.


CONCLUSIONS
There is no difference in efficacy to experimental hypersensitivity between the largest approved dose of intrathecal adenosine and a dose 25% this size, but side effects are more common with the larger dose. Failure of aminophylline to reverse adenosine's effects could reflect inadequate concentrations at receptors in the spinal cord after intravenous injection.
D000241:Adenosine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000287:Administration, Topical; D000328:Adult; D000628:Aminophylline / Q000008:administration & dosage / Q000494:pharmacology; D018712:Analgesics, Non-Narcotic; D001794:Blood Pressure / Q000187:drug effects; D002211:Capsaicin; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006358:Hot Temperature; D006801:Humans; D006930:Hyperalgesia / Q000139:chemically induced / Q000175:diagnosis; D006967:Hypersensitivity / Q000503:physiopathology; D007262:Infusions, Intravenous; D007278:Injections, Spinal; D008297:Male; D008875:Middle Aged; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy*; D010147:Pain Measurement / Q000187:drug effects; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D058915:Purinergic P1 Receptor Antagonists
D018712:Analgesics, Non-Narcotic; D010726:Phosphodiesterase Inhibitors; D058915:Purinergic P1 Receptor Antagonists; D000628:Aminophylline; D000241:Adenosine; D002211:Capsaicin