The long-lasting analgesic effect of oxycodone is reversed by i.t. injection of a GABA_B antagonist.

<p>A: Schematic representation of the experimental paradigm. Rats received i.p. injection of vincristine (black horizontal bar). The oxycodone treatment started at D15, while animals presented mechanical hyperalgesia (dark grey horizontal bar). Behavioural tests, illustrated by black triangles, were performed at D0 (BL), D15 and D19, before (T0) and 30 min after (T30) oxycodone injection, to control for the analgesic effect of oxycodone. The functional involvement of GABA_B receptors in this long-asting analgesic effect of oxycodone was tested by intrathecal (i.t.) injection of saclofen (10 μg) versus saline injection (grey arrow), 4 hours after the previous test (D19). Rats were injected again with oxycodone or saline (D19′). Fifteen minutes after this second injection, rats were injected intrathecally with saclofen or saline and tested 15 minutes after the i.t. injection (T30′). B, C: Effect of saclofen intrathecal injection on oxycodone's long-lasting effect on static mechanical allodynia (B) and static mechanical hyperalgesia (C). Results are expressed as mean δ withdrawal threshold ± SEM. The δ-withdrawal threshold was calculated using individual values as follows: at D19 and at D19′. The results confirm the analgesic action of oxycodone (left panel, D19), and show that saclofen completely reversed the analgesic action on mechanical allodynia (B), while only partially reversing the effect on static mechanical hyperalgesia (C). (n = 6, vincristine-oxycodone-saclofen treated rats; n = 6, vincristine-oxycodone-saline treated rats; n = 6 vincristine-saline-saclofen treated rats; n = 6, vincristine-saline-saline treated rats). ***p<0.001: vincristine-oxycodone treated rats compared at different time points; ## P<0.01, ### p<0.001: vincristine-oxycodone treated rats vs. vincristine-saline treated rats; °°p<0.01, °°°p<0.001: vincristine-oxycodone-saclofen treated rats vs. vincristine-oxycodone-saline treated rats; ††† p<0.001: vincristine-oxycodone-saclofen treated rats vs. vincristine-saline-saclofen treated rats.