TY - JOUR
T1 - Antinociceptive effects of rotigotine-loaded microspheres and its synergistic interactions with analgesics in inflammatory pain in rats
AU - Li, Ting
AU - Wang, Tian
AU - Wang, Linlin
AU - Liu, Rongxia
AU - Zhang, Leiming
AU - Zhai, Rong
AU - Fu, Fenghua
N1 - Funding Information:
This work was supported by national new medicine major special natural medicine and new preparation synthesis platform (2013ZX09402201) and grants of the Taishan Scholar Project of China. We thank Joe Barber Jr., PhD, from Liwen Bianji, Edanz Editing China ( www.liwenbianji.cn/ac ), for editing the English text of a draft of this manuscript.
PY - 2020
Y1 - 2020
N2 - Rotigotine-loaded microspheres (RoMS) are sustained-release formulations with prolonged anti-Parkinson's effects. Given that pain is a non-motor symptom of Parkinson's disease, this study investigated the antinociceptive effects of RoMS and their synergistic effects with analgesics on inflammatory pain. A model of inflammatory pain was prepared by intraplantarly injecting male Sprague-Dawley rats with carrageenan. The antinociceptive effects of RoMS, acetaminophen, and tramadol, both alone and in combination, were evaluated using the hind paw withdrawal latency in the hot plate test and Randall–Selitto test. The rotigotine concentrations in serum and tissues were assayed using ultra-performance liquid chromatography–tandem mass spectrometry. Isobolographic analysis was performed to evaluate the nature of the interactions of RoMS with acetaminophen or tramadol. The results showed that hind paw withdrawal latency to thermal and mechanical stimuli was significantly increased on day 3 and 7 after administered RoMS. Rotigotine could be detected in serum and tissues 3 and 7 days after an intramuscular injection of RoMS. However, the rotigotine concentration fell the detection limit of the assay on day 14 after administration. RoMS produced synergistic antinociceptive effects in the inflammatory pain model when RoMS is combined with acetaminophen or tramadol. These findings suggest that RoMS can relieve inflammatory pain in rats. Furthermore, the combination of RoMS with acetaminophen or tramadol produces synergistic antinociception, which may be clinically worthy because combination therapies may reduce the drug doses required for antinociception.
AB - Rotigotine-loaded microspheres (RoMS) are sustained-release formulations with prolonged anti-Parkinson's effects. Given that pain is a non-motor symptom of Parkinson's disease, this study investigated the antinociceptive effects of RoMS and their synergistic effects with analgesics on inflammatory pain. A model of inflammatory pain was prepared by intraplantarly injecting male Sprague-Dawley rats with carrageenan. The antinociceptive effects of RoMS, acetaminophen, and tramadol, both alone and in combination, were evaluated using the hind paw withdrawal latency in the hot plate test and Randall–Selitto test. The rotigotine concentrations in serum and tissues were assayed using ultra-performance liquid chromatography–tandem mass spectrometry. Isobolographic analysis was performed to evaluate the nature of the interactions of RoMS with acetaminophen or tramadol. The results showed that hind paw withdrawal latency to thermal and mechanical stimuli was significantly increased on day 3 and 7 after administered RoMS. Rotigotine could be detected in serum and tissues 3 and 7 days after an intramuscular injection of RoMS. However, the rotigotine concentration fell the detection limit of the assay on day 14 after administration. RoMS produced synergistic antinociceptive effects in the inflammatory pain model when RoMS is combined with acetaminophen or tramadol. These findings suggest that RoMS can relieve inflammatory pain in rats. Furthermore, the combination of RoMS with acetaminophen or tramadol produces synergistic antinociception, which may be clinically worthy because combination therapies may reduce the drug doses required for antinociception.
KW - Antinociception
KW - Dopamine
KW - Pain
KW - Rotigotine-loaded microspheres
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U2 - 10.1016/j.ejphar.2020.173693
DO - 10.1016/j.ejphar.2020.173693
M3 - Article
C2 - 33160937
AN - SCOPUS:85096370166
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
SN - 0014-2999
M1 - 173693
ER -