How chronic pain affects the development of opioid tolerance has been a controversial issue from both dinical and scientific perspectives for the past 25 years. Some studies have shown that chronic pain inhibits the development of opioid tolerance(Colpaert, 1978; Colpaert et al., 1978, 1980; Portenoy and Foley, 1986; Portenoy et al., 1986; Sherman et al., 1981; Vaccanno et al., 1993), whereas others have concluded that pain does not affect or accentuates tolerance development(Connell et al., 1994; Gutstein et al., 1993, 1995; Houde et al., 1966; Kayan et al., 1969; Kayser and Guilbaud, 1985; Onofrio and Yaksh, 1990). This apparent contradiction has been difficult to reconcile. The two positions have very different implications, both mechanistically and in terms of clinical treatment. Dr. Colpaert, a long-time proponent of the idea that pain inhibits tolerance development, has proposed a new theory ofopioid action in an effort to provide a theoretical framework for his data and to explain conflicting results.

His theory is based on the underlying assumption that tolerance th opioids does not exist. Instead, it is proposed that chronic opioid administration causes hyperalgesia. The opioid maintains its effectiveness, but the hyperalgesia creates the impression that the opioid has become less effective. Chronic pain is postulated to cause hypoalgesia, leading to the conclusion that opioids are more effective in chronic pain states. Another assumption of this model is the concept that the perception of pain is proportional to the difference between the signal caused by a noxious stimulus and the “baseline” signal intensity, which is the average signal received by the “system” in the pain-free state. For a theory to serve as an accurate framework ex-plaimng physical phenomena, three conditions must be satisfied:(1) the underlying assumptions must be sound,(2) the hypotheses must adequately account for all available experimental data, and (3) alternate explanations must be considered and either refuted or effectively redonciled with the proposed theory. The preceding review (Colpaert, 1996) has an unique perspective on this sub-ject and raises many interesting points worthy of further