Antinociception following implantation of mouse B16 melanoma cells in mouse and rat spinal cord

Abstract

B16 F1C29 melanoma cells, which are thought to contain and release catecholamines, were implanted in mouse and rat spinal subarachnoid space. B16 F1C29 cell implants augmented the antinociceptive effect of morphine in tail-flick test, and this interaction was blocked by either the α 2-adrenergic antagonist idazoxan or the opioid antagonist naloxone. B16 F1C29 cell implants also augmented the antinociceptive effect of the catecholamine re-uptake blocker desipramine. Substance P-induced biting and scratching behaviors were inhibited in mice receiving B16 F1C29 cell implants, and this effect of B16 F1C29 cell implants was blocked by the α 2-adrenergic antagonist idazoxan. Mice receiving B16 F1C29 cell implants showed tolerance to intrathecal administration of the α 2-adrenergic agonist UK 14304. These results suggest that B16 cell implant-induced antinociception was mediated by catecholamines secreted from the cell implants and acting at spinal α 2-adrenergic receptors. Spinal implantation of catecholamine-releasing cells may provide an alternative approach for the therapy of chronic intractable pain and a useful model to study α 2-adrenergic receptor tolerance.