Intrathecal adenosine increases spinal cord blood flow in the rat: measurements with the laser-Doppler flowmetry technique.

Abstract

Adenosine and adenosine analogues induce antinociception both after systemic and intrathecal (i.t.) administration in animal models. Further, patients with neuropathic pain have been treated successfully with i.t. adenosine. Prior to introducing new analgesic drugs for regular spinal use in humans, experimental studies must be undertaken to evaluate the risks of neurotoxicity. It is important to evaluate the possibility of cytotoxic effects and that antinociception may be due to decreased spinal cord blood flow (SCBF) and neural ischaemia. The present study evaluates whether adenosine or isotonic mannitol induces changes in SCBF as assessed by laser-Doppler flowmetry (LDF). After laminectomy and insertion of i.t. catheters, seven rats received adenosine 50 microg in isotonic mannitol 500 microg, six rats received isotonic mannitol 500 microg and eight rats received saline 0.9%. SCBF was registered by the LDF technique continuously for 3 h after injection. Arterial blood pressure was also assessed. In the adenosine in mannitol group, SCBF increased up to 230% of baseline levels for almost 40 min, P = 0.044 and then declined. In the mannitol group, SCBF increased up to 180% of baseline (P < 0.011) before declining. At 60 min, SCBF had returned to saline levels and remained stable during the rest of the experiment. Intrathecal administration of adenosine in mannitol and of mannitol both increased SCBF in rats, compared with saline. It is unlikely that the effects on SCBF induced by adenosine and mannitol could result in neurotoxicity of the spinal cord.