This study investigated the cutaneous antinociceptive effects of tyramine and octopamine and their respective interactions with co-injection of lidocaine and compared them with noradrenaline. Cutaneous antinociceptive effects in rats was assessed through the blockage of cutaneous trunci muscle reflexes induced by needle pinpricks. Isobolographic analysis was used to assess the interaction between lidocaine and each drug. The results showed that at the ED75 (75% effective dose), tyramine and lidocaine caused 73% and 77% nociceptive blockade, respectively. The order of drug potency (ED50) is noradrenaline > lidocaine > octopamine > tyramine (p<0.01). Isobolographic analysis shows that the experimental ED50 of the octopamine-lidocaine combination or noradrenaline-lidocaine combination is significantly lower than the theoretical ED50 (p<0.01), showing a synergistic effect, while the tyramine-lidocaine combination shows an additive effect. When phentolamine (0.06 µmole) was added to tyramine-lidocaine, octopamine-lidocaine or noradrenaline-lidocaine combinations, the blocking effect was similar to lidocaine alone (ED95), showing phentolamine inhibited synergy. In summary, subcutaneous tyramine and octopamine have dose-dependent antinociceptive effects and that the synergistic effect of octopamine-lidocaine and noradrenaline-lidocaine is mediated by α-adrenergic receptors.

Ching-Hsia Hung has completed his PhD at the age of 28 years from National Yang Ming Chiao Tung University, Taiwan. Ching-Hsia Hung was a professor in the Department of Physical Therapy at National Cheng Kung University in Taiwan. Her research interest is in the fields of exercise effect and physiology, pharmacology and systemic effect of analgesic agents, and pain science. She has published more than 100 papers in reputed journals and has been serving as an editorial board member of repute.