Abstract
Chronic pain of various origins is a major health care issue affecting a large patient population,
also bring significant social and economic cost on the society. Work presented in this thesis
concerns novel methods of treatments for chronic pain using experimental models. Sinomenine
is a chemical compound isolated originally from the root of the plant Sinomenium Acutum
native to China and Japan. It is an alkaloid, structurally belongs to the morphine family. The
root of Sinomenium Acutum, known as Qingteng, has been traditionally used in China as a
medical remedy for condition likely to be rheumatism. Sinomenine is currently approved in
China as an anti-rheumatic agent for clinical sue.
In first part of the thesis, we studied the analgesic effect of sinomenine in chronic experimental
pain models of neuropathic and arthritic pain. We showed that sinomenine has significant
analgesic effects in rat and mouse models of neuropathic pain as well as in a mouse model
(collagen antibody-induced arthritis model, CAIA) of arthritic pain. More importantly, the
effect of sinomenine on neuropathic and arthritic pain is maintained upon repeated chronic
administration without signs of tolerance or dependence.
In the second part of the thesis, we examined the possible application of sinomenine as an
analgesic, we showed that combination with sinomenine with gabapentin, a clinically used drug
treating neuropathic pain, produced marked synergistic interaction in rat and mouse models of
neuropathic pain and such synergism can still be observed upon repeated administration
without signs of tolerance and dependence. We can also show a similar synergistic interaction
between gabapentin and dextromethorphan, a low affinity non-competitive NMDA antagonist.
The work presented in this thesis suggested that sinomenine could be explored as a novel
analgesic in treating neuropathic and arthritic pain. The results also showed combination
therapy involving sinomenine, gabapentin and dextromethorphan might be useful in the clinic.
The potential mechanisms for the effect of sinomenine and its interaction with other analgesics
need to be further studied.
