Synergism between opioids and other agents at central primary afferent synapses

Funded Activity Summary

Opioids, such as codeine, pethidine and morphine, are the most effective pain relieving drugs known but their clinical utility is limited by hazardous and potentially lethal side effects, as well as the development of tolerance and physical dependence with associated addiction liability. Recent research in our laboratory has identified for the first time a mechanism in the mammalian brain by which the pain relieving actions of opioids can be greatly enhanced by drugs that independently modulate biochemical processes distinct from those altered by opioids. Exploitation of these mechanisms has great potential for the development of new pharmacotherapies for effective pain relief with minimised side effects. These synergistic mechanisms appear to be at least as important for pain relief in the spinal cord as in brain, so the proposed studies will first examine the basis for synergism with opioid mediated pain relief in spinal cord. There is also strong evidence that the mechanisms to be studied in the proposed work are pivotal in the development of debilitating, chronic pain conditions that involve heightened sensitivity to painful stimuli and-or painful responses to normally innocuous stimuli such as light touch. Such aberrant responses can persist long after initial tissue damage has recovered. It is known that opioids can limit somewhat the initial steps in the induction of these abnormal responses but the mechanisms involved are unknown. The proposed studies will contribute to resolution of these mechanisms. Better understanding of the basis of these pathological processes will lead to better strategies for retarding or preventing the development of chronic pain conditions.

Funded Activity Details

Start Date: 01-01-2000

End Date: 01-01-2002

Funding Scheme: NHMRC Project Grants

Funding Amount: $202,771.00

Funder: National Health and Medical Research Council

Research Topics

ANZSRC Field of Research (FoR)

Medical biochemistry - carbohydrates

ANZSRC Socio-Economic Objective (SEO)

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Other Keywords

analgesia | analgesics/ non narcotic | arachidonic acid | hyperalgesia | neuropathic pain | opioid analgesics | opioid receptors | substantia gelatinosa | synaptic transmission

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