Veterinary Pharmacology Laboratory
Current Projects
Synergy between opioids, alpha2 agonists, and cannabinoids in pain perception
Several pain pathways have been identified in the central nervous system, and many analgesics (i.e. pain-relieving drugs) are known to specifically work on particular pathways. In fact, certain pathways may overlap and therefore different analgesics may interact with each other. Our studies in mice have identified synergy between different analgesics, so that an analgesic effect significantly greater than that expected if the effect were simply additive, is achieved. These observations have clearly important clinical application, and may help to further elucidate the complex mechanisms of pain perception.
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Pharmacological mechanisms involved in chronic pain
Currently available analgesics provide limited relief from chronic intractable pain, because of problems of dependence , tolerance or other unacceptable side effects.
Our research is directed at investigating in experimental animals, the potential of novel antinociceptive agents to provide pain relief with decreased side effects. Analgesic effects of novel cannabinoid receptor agonists and other analgesics are being assessed in acute pain models (tail flick and hot plate) as well as chronic pain models (nerve ligation that causes causing allodynia or altered sensation in the foot pad). Possible synergistic effects between analgesics used in combination are being investigated, as well as cardiovascular and behavioural side effects.
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Bone Cell Biology- Intracellular signalling in response to thrombin treatment of osteoblasts
(In collaboration with Associate Professor Mackie’s Bone Cell Biology Laboratory)
Bone diseases such as osteoporosis result from alterations in the balance of activity of bone-forming cells (osteoblasts) and bone-resorbing cells (osteoclasts). It is therefore of critical importance to understand the factors that influence the number of osteoblasts available for bone formation, and how they can be manipulated pharmacologically.
As well as its role in haemostasis and thrombosis, thrombin acts as an agonist for a number of cellular responses. Thrombin treatment of osteoblasts has been shown to stimulate proliferation and inhibit differentiation and apoptosis of treated cells. Previously we have shown that thrombin inhibits osteoblast apoptosis by a mechanism involving the secretion of a second diffusible survival factor. Preliminary studies indicate that prostaglandin production is required for thrombin’s effect.
Using tissue culture techniques, this project aims to characterise the sequence of events leading to prostaglandin production and its role in inhibiting osteoblast apoptosis.
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Bone Cell Biology- the Role of Tenascin-C in Bone and Joint Pathology
(In collaboration with Associate Professor Mackie’s Bone Cell Biology Laboratory)
Tenascin –C is an extra-cellular matrix protein with multiple roles in regulation of cell behaviour in a variety of tissues. It is secreted by osteoblasts and present on bone surfaces. The requirement for this protein in bone turnover is currently being investigated in ovariectomized tenascin-C-knockout and wild type mice.
harmacology Laboratory also provide expertise in the delivery of post graduate medical and surgical courses and workshops conducted in the Department of Pharmacology by the Royal Australian College of Surgeons, and The Department of Surgery, Royal Melbourne Hospital .
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