Mapping pain pathways with Northern Queensland cone shell neuropeptides

The cone shell snails found on beaches in Queensland have over 500 species, with as many as 50, 000 unique CNP’s. These CNP’s are extremely powerful, with activity at most of the receptors and ion channels proposed to be important for pain. Less than 0.1% of these highly selective CNP’s have been described in detail.

However PMRI scientists, led by Prof Mac Christie, are working with scientists at the University of Queensland who have high-level expertise in investigating cone shell CNP’s, their structure and their possible sites of action.

PMRI then takes promising CNP’s and investigates where they work in the pain pathway and how effective they are in different pain problems such as: pain due to injury to the sciatic nerve (sciatica); pain due to spinal cord injury (SCI); arthritis pain (inflammatory pain); cancer pain; pelvic pain (eg. bladder pain).

Two highly promising CNPs have already progressed to initial investigation in people with cancer pain. One CNP acts on the adrenaline system in the spinal cord which is know to be powerful in modifying pain. Early results in severe cancer pain are very promising.

A second CNP acts in a highly selective manner on a special sodium (Na⁺) channel that is only found on  nerve fibers involved in pain. This is a major advance over existing Na⁺ channel drugs, such as lignocaine which have non-selective effects on a wide range of nerve fibers and nerve cells including those in the brain and heart and those controlling muscles.

These unwanted effects can cause serious side effects such as convulsions, low blood pressure and inability to walk. The new CNP have at least a ten-fold ‘safety margin’ over existing drugs and is much more powerful, particularly for nerve damage pain, which is present in a large number of patients such as those with sciatica, spinal cord injury, cancer, and many types of nerve injury pain. This new CNP acts on the NaV_1.8 Na⁺ channel and has a powerful specific effect on a key aspect of the ‘disease process’ of SCI pain.

Other CNP’s acting at other sites in the pain pathway are currently under investigation using state of the art techniques at behavioural, cellular, and sub-cellular/ molecular levels.

About 35 scientists at PMRI are collaborating with the University of Queensland, University College London, and University Nagasaki, Japan. The basic research program is closely linked to a very active Clinical Research Program with facilities for 1^st use in human studies (Phase I) and subsequent patient studies (Phases II and III). Such studies are carried out by more than 40 multidisciplinary clinical staff of the Pain Management Research Centre (PMRC), closely linked to PMRI, and responsible for over 40, 000 episodes of patient care per year.

Group Leader

Prof MacDonald Christie

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