Theophylline-induced nociceptive behavioral response in mice: Possible indirect interaction with spinal [formula omitted] receptors

Abstract

Intrathecal administration of an adenosine receptor antagonist, theophylline, elicited nociceptive behavior such as licking, biting and scratching in mice. This behavioral response was dose-dependently reduced by simultaneous injection of an adenosine receptor agonist, 5′- N 6-ethylcarboxamidoadenosine, or a selective N- methyl- d- aspartate (NMDA) receptor antagonist, d-2-amino-5-phosphonovalerate. This theophylline-induced behavior was not significantly reduced by the substance P (SP) analogue, the neurokinin receptor antagonist, [ d-Arg 1, d-Trp 7,9, Leu 11]SP (spantide). These results suggest the possibility that theophylline-induced nociceptive behavior may be mediated through interactions with both spinal adenosine- and NMDA receptors separately, or only through interaction(s) with adenosine receptors localized on the axon terminals of excitatory amino acid neurons. Present data have failed to reveal involvement of SP.