Sir

J. J. Cox and colleagues present an exciting aspect of using drugs targeting SCN9A as analgesic agents, in their Article “An SCN9A channelopathy causes congenital inability to experience pain” (Nature 444, 894–898; 2006). As clinicians, we need better tools to treat the high prevalence of non-malignant chronic pain syndromes such as back pain, arthritis, fibromyalgia, migraines and irritable bowel syndrome. These afflict a large number of people and severely reduce their quality of life, as well as creating a vast financial burden.

Several novel analgesics, targeting pain-specific molecular transduction pathways, are at various levels of clinical and preclinical development. The high drug specificity potentially allows profound pain relief without the dose-limiting toxicities seen with current drugs. But what if these medicines are even better than expected?

Pain is a protection mechanism, serving to prevent injury, deter repetitive harmful behaviour and allow healing. It is usually the first indication of disease or trauma that triggers the individual to seek treatment. Our current approaches to treating pain often provide effective relief, but it is 'incomplete', in that activity-related breakthrough pain continues — and this can be useful.

The problem will arise with long-term use of a potentially perfect analgesic drug to alleviate a specific symptom, such as chronic back pain. The medications that block the targeted pain generator could also prevent the warning pain caused by a new, more serious condition such as stroke, myocardial infarction or bowel obstruction. The results could be catastrophic: diagnosis may be delayed, leading to irreversible damage, long-term disability or worse.

Using a perfect analgesic to relieve pain from sports injuries such as sprain, repetitive injury or overuse may allow the athlete to ignore the bio-warning signs of pain, impair the healing process and risk more serious injury.

Should we be deterred from the search for superior pain medications? In patients with advanced life-threatening disease seeking palliation, the question is easily answered: no. But a young patient with disabling lower-back pain on chronic medication presents a different situation. Relieving the back pain may restore function, but could hinder the rapid diagnosis of life-threatening disease.

Our choice is whether to limit the use of these medications to a defined population, on the basis of risk assessment, or to embrace these innovations and attempt to adjust the practice of medicine fast enough to accommodate the potential consequences. In the latter case, clinicians would have to remove 'pain' from the list of symptoms currently used in diagnosis. For instance, myocardial infarction may present with more flu-like symptoms — sudden onset of nausea, weakness, diaphoresis and shortness of breath, instead of the classically described patient clutching his or her chest. Appendicitis and bowel perforation may present with painless nausea, vomiting and loss of appetite.

On the other hand, denying a known therapy to a patient with unrelenting pain is difficult to accept, when a novel analgesic could normalize function, improve quality of life, reduce the financial impact by replacing ineffective treatments and allow an earlier return to work.

The dilemma outlined here, although theoretical, should be considered before these therapies are approved. If these much-needed therapeutic advances are to be used in a truly effective fashion, anticipating and preventing any possible untoward events could facilitate their safe implementation. Data collected in clinical trials would be helpful in determining the importance of this response.