Goodchild C S, Guo Z, Freeman J, Gent J P
Department of Anaesthesia, University of Leeds, UK.
Br J Anaesth. 1997 May;78(5):563-9. doi: 10.1093/bja/78.5.563.
The antinociceptive effects of intrathecal 5-HT, fentanyl, ICI197067 and U50488H were assessed by electrical current nociceptive threshold and tail flick latency measurements. Equieffective doses of these agonists were then given intrathecally with a range of doses of naloxone or the highly selective mu opioid antagonist, beta-funaltrexamine. Antagonist dose-response curves were plotted. Other rats were made tolerant to either fentanyl or 5-HT by intrathecal injections of these drugs seven times daily and the antinociceptive effects of intrathecal fentanyl and 5-HT were assessed in each group. All intrathecal drugs caused spinally mediated antinociception in both tests. The antinociceptive effects of intrathecal 5-HT assessed by the electrical test (ECT) but not by tail flick latency (TFL) were suppressed by both opioid antagonists at doses similar to those required to suppress all of the effects of intrathecal fentanyl. The ED50 values were 0.22 (fentanyl, ECT), 0.25 (fentanyl, TFL) and 0.18 (5-HT, ECT) mumol kg-1 for naloxone and for beta-funaltrexamine 2.2 fmol (5-HT, ECT), the same order as that required to produce similar suppression of the antinociceptive effects of fentanyl (46 amol: fentanyl, ECT; 4.6 fmol: fentanyl, TFL) and very different from the ED50 for beta-FNA suppression of the antinociceptive effects of the kappa opioid, U50488H (5.88 pmol). Cross tolerance in both directions was demonstrated between intrathecal fentanyl and 5-HT in the electrical test but not in the tail flick test. We conclude that intrathecal 5-HT caused spinally mediated antinociceptive effects revealed by electrical current and tail flick latency tests. The antinociceptive effects in the electrical test involved spinal cord mu opioid receptors.
通过电流伤害性感受阈值和甩尾潜伏期测量，评估鞘内注射5-羟色胺（5-HT）、芬太尼、ICI197067和U50488H的抗伤害感受作用。然后将这些激动剂的等效剂量与一系列剂量的纳洛酮或高选择性μ阿片受体拮抗剂β-氟奈曲胺鞘内注射给药。绘制拮抗剂剂量-反应曲线。通过每天鞘内注射这些药物7次，使其他大鼠对芬太尼或5-HT产生耐受性，并评估每组中鞘内注射芬太尼和5-HT的抗伤害感受作用。在两项试验中，所有鞘内注射药物均引起脊髓介导的抗伤害感受。在电刺激试验（ECT）中评估的鞘内5-HT的抗伤害感受作用，但在甩尾潜伏期（TFL）试验中未观察到，两种阿片受体拮抗剂在抑制鞘内芬太尼所有作用所需的相似剂量下均可抑制该作用。纳洛酮的半数有效剂量（ED50）值分别为0.22（芬太尼，ECT）、0.25（芬太尼，TFL）和0.18（5-HT，ECT）μmol·kg-1，β-氟奈曲胺的ED50值为2.2 fmol（5-HT，ECT），与抑制芬太尼抗伤害感受作用所需的顺序相同（46 amol：芬太尼，ECT；4.6 fmol：芬太尼，TFL），与β-氟奈曲胺抑制κ阿片受体激动剂U50488H抗伤害感受作用的ED50（5.88 pmol）非常不同。在电刺激试验中，鞘内芬太尼和5-HT之间双向交叉耐受，但在甩尾试验中未观察到。我们得出结论，鞘内注射5-HT通过电流和甩尾潜伏期试验显示出脊髓介导的抗伤害感受作用。电刺激试验中的抗伤害感受作用涉及脊髓μ阿片受体。
