Chronic neuropathic pain — ABT-594

Pain is the body's way of telling us there is something wrong. Acute pain from injury or illness usually resolves itself quickly, but if it persists for longer than six months it is classified as chronic pain. Chronic pain results from various ongoing diseases or conditions, such as cancer or osteoarthritis; but it can sometimes carry on long after physical recovery from any trauma or illness. In such cases, the fault lies with the nervous system, which is continuing to transmit pain signals to the brain, despite the fact that there is no physical cause remaining.

The severity of the symptoms can vary from a slight tingling sensation through to overwhelming, debilitating pain. But standard painkillers, such as non-steroidal anti-inflammatory drugs or opiates, do not have any great effect, so drugs with a different mechanism of action must be used. Among the pathways being investigated as possible treatment routes are the nicotinic acetylcholine receptors, or nAChRs, which exist in various different subtypes. One of the first compounds to be developed that acts at these receptors, epibatidine, has an analgesic effect at least a hundred times greater than that of morphine. However, it is very unselective, as it acts as a full agonist at at least five different nAChR subtypes, leading to a range of undesirable side-effects, particularly in the central nervous, gastrointestinal, respiratory and cardiovascular systems.

In a search for more selective compounds, Abbott Laboratories has discovered a compound, coded ABT-594¹ which, although it is a full agonist for several nAChR receptors, has enhanced selectivity for the α₄β₂ subtype, and it is now being investigated further as a treatment for neuropathic pain.

An additional potential advantage of the drug is that it may not be as addictive as opiates: tests in rats have shown that it does not lead to opioid type withdrawal effects once treatment is stopped². It shows anti-inflammatory effects³, and may also be a neuroprotective, and could conceivably be of use in the treatment of Parkinsonism and Alzheimer's disease⁴. The compound is currently undergoing Phase II clinical trials and, if successful, could prove a promising therapy for the treatment of this difficult to treat and often severe form of pain.