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. 2022 Nov 23;13:1023611. doi: 10.3389/fphar.2022.1023611

FIGURE 3.

FIGURE 3

Role of spinal α2A-adrenoceptors in the clonidine-induced behavioral antinociception and the antinociceptive effect of JP 1302 (α2C-adrenoceptor antagonist). (A) shows the effect of intrathecal (i.t.) injection of vehicle (10 μl; isotonic saline solution) or α2A/2B/2C-adrenoceptor antagonists on the clonidine-induced inhibition of the flinches induced by formalin (1%; 50 μl, s.c.) during phase I (P1) and phase II (P2). Vehicle, BRL 44408 (0.1 or 1 nmol; an α2A-adrenoceptor antagonist; n = 5 each dose), imiloxan (10 nmol; an α2B-adrenoceptor antagonist; n = 5), or JP 1302 (1 nmol; an α2C-adrenoceptor antagonist; n = 5) were given i.t. 10 min prior clonidine. (B,C) represent the data as the area under the mean number of flinches against the curve (AUC) and show that BRL 44408 (1 nmol) inhibited the clonidine-induced antinociception in both phases (P1, P2). During P2, JP 1302 seems to enhance (statistically non-significant, p > 0.05) the antinociception induced by clonidine. (D) shows the per se effect of BRL 44408 (n = 5 each dose), imiloxan (n = 5), or JP 1302 (n = 5 each dose) in rats submitted to the 1% formalin test. The AUC in (E,F) suggest that BRL 44408 and imiloxan do not affect formalin-induced nociception. In contrast, JP 1302 diminishes the AUC values during both phases (P1, P2), suggesting an antinociceptive effect.