Agonists at the µ-opioid receptor inhibit synaptic transmission throughout the brain and spinal cord. In the spinal dorsal horn, it has been suggested that µ-opioid agonists can also cause the release of adenosine, possibly by modulation of nucleoside transporters (Sweeney et al. 1993). However, the functional consequences of this release are unclear. We have used electrophysiological methods to assess whether µ-opioid-mediated release of adenosine impacts on synaptic processing in the superficial spinal dorsal horn in vitro.
Slices (300 µm) of lumbar spinal cord were obtained from 12- to 15-day-old Wistar rats irreversibly anaesthetised with urethane (I.P. 2 mg kg-1). Whole cell patch clamp recordings were made from neurons within lamina II. Excitatory postsynaptic currents (EPSCs) were evoked in the presence of 30 µM bicuculline and 10 µM strychnine using a bipolar stimulating electrode placed onto the dorsal root entry zone. The µ-opioid receptor agonist [D-Ala2,N-MePhe4,Gly-ol5]-enkephalin (DAMGO;1 µM), the adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; 1 µM) and the opioid antagonist naloxone (10 µM) were bath applied. Data are expressed as the mean percentage inhibition of control ± S.E.M.
Application of DAMGO inhibited the EPSC by 32.9 ± 3.0 %. This inhibition was partially reversed to 13.1 ± 4.0 %, by co-application of DPCPX (P < 0.01, Student’s paired t test, n = 7). Neither DPCPX nor naloxone had an effect on the EPSC amplitude when applied alone. In the presence of naloxone, DAMGO failed to produce an inhibition of the evoked EPSC -2.9 ± 4.7 %, n = 6) suggesting that the effect of DAMGO was mediated specifically through opioid receptors rather than acting directly at adenosine receptors.
These data suggest therefore, that a component of opioid-mediated inhibition within substantia gelatinosa is via presynaptic A1 adenosine receptors. This is consistent with the proposal that µ-opioid receptor activation results in a release of adenosine (Sawynok et al. 1989) thereby further enhancing opioid-mediated inhibition of nociceptive transmission.
This work was supported by the MRC, UK.