TY - JOUR
T1 - Isobolographic analysis of the cutaneous antinociceptive interaction between bupivacaine co-injected with serotonin in rats
AU - Tzeng, Jann Inn
AU - Chiu, Chong Chi
AU - Wang, Jhi Joung
AU - Chen, Yu Wen
AU - Hung, Ching Hsia
N1 - Publisher Copyright:
© 2017 Institute of Pharmacology, Polish Academy of Sciences
PY - 2017/10
Y1 - 2017/10
N2 - Background The aim of this experiment was to investigate a long-lasting local anesthetic bupivacaine combined with serotonin at inducing cutaneous antinociception. Methods The skin antinociception, characterized by an inhibition of the cutaneous trunci muscle reflex (CTMR) following the pinprick on the dorsal skin of rats, was evaluated. The cutaneous antinociceptive effects of bupivacaine alone, serotonin alone, or bupivacaine co-injected with serotonin in a dose-dependent fashion were constructed, while the drug–drug interactions were evaluated by isobologram. Results Subcutaneous serotonin, as well as the local anesthetic bupivacaine provoked dose-related cutaneous antinociception. On an equipotent basis (50% effective dose [ED50]), the relative potency was bupivacaine (0.43 [0.37–0.50] μmol) > serotonin (1.27 [1.15–1.40] μmol) (p < 0.01). At the equi-anesthetic doses (ED75, ED50 and ED25), the duration of bupivacaine was similar to that of serotonin at producing cutaneous antinociceptive effects. Co-administration of bupivacaine and serotonin displayed a synergistic antinociception. Conclusions The preclinical data demonstrated that serotonin is less potent in eliciting cutaneous antinociceptive effects but has the similar duration of action, compared with bupivacaine. We also found a more significant depth of the sensory block with bupivacaine + serotonin than bupivacaine alone.
AB - Background The aim of this experiment was to investigate a long-lasting local anesthetic bupivacaine combined with serotonin at inducing cutaneous antinociception. Methods The skin antinociception, characterized by an inhibition of the cutaneous trunci muscle reflex (CTMR) following the pinprick on the dorsal skin of rats, was evaluated. The cutaneous antinociceptive effects of bupivacaine alone, serotonin alone, or bupivacaine co-injected with serotonin in a dose-dependent fashion were constructed, while the drug–drug interactions were evaluated by isobologram. Results Subcutaneous serotonin, as well as the local anesthetic bupivacaine provoked dose-related cutaneous antinociception. On an equipotent basis (50% effective dose [ED50]), the relative potency was bupivacaine (0.43 [0.37–0.50] μmol) > serotonin (1.27 [1.15–1.40] μmol) (p < 0.01). At the equi-anesthetic doses (ED75, ED50 and ED25), the duration of bupivacaine was similar to that of serotonin at producing cutaneous antinociceptive effects. Co-administration of bupivacaine and serotonin displayed a synergistic antinociception. Conclusions The preclinical data demonstrated that serotonin is less potent in eliciting cutaneous antinociceptive effects but has the similar duration of action, compared with bupivacaine. We also found a more significant depth of the sensory block with bupivacaine + serotonin than bupivacaine alone.
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U2 - 10.1016/j.pharep.2017.03.017
DO - 10.1016/j.pharep.2017.03.017
M3 - Article
C2 - 28623708
AN - SCOPUS:85020721221
SN - 1734-1140
VL - 69
SP - 846
EP - 850
JO - Pharmacological Reports
JF - Pharmacological Reports
IS - 5
ER -