Relationships between increased vascular permeability, oedema, hyperalgesia and the effect of non-steroid anti-inflammatory drugs

Abstract

The relationship between oedema, increased permeability and hyperalgesia has been a matter of debate for some time. On one side there are those who concluded that oedema formation and protein leakage are closely linked.^l,2, but others have evidence indicating that the processes are independent^3,4,5. A parallelism between the development of oedema and an increase in permeability during the development of inflammation induced by carrageenan was found in studies utilizing labelled protein⁶’⁷. However, Garcia Lerne et al.⁸ did not find this parallelism during the entire period of observation. When they measured the seepage of protein-bound Evans Blue into a perfusate (coaxial perfusion), they found that the major increase in permeability occurred in the early stages but that only a small residual increase in permeability was demonstrable at the time oedema was maximal (4th hour). These investigators also showed that non-steroid anti-inflammatory drugs, which are prostaglandin synthesis inhibitors, were only effective when given before administration of carrageenan. This observation is not consistent with the suggestion that prostaglandins are the mediators of the late phase of carrageenan oedema⁶’⁹. In addition, non-steroid anti-inflammatory drugs such as aspirin and phenylbutazone were shown to be effective in blocking oedema when given 2 h after carrageenan¹⁰. Hyperalgesia, on the other hand, had been shown to be more sensitive to curative treatment with aspirin-like drugs than oedema, and that oedema per se does not cause hyperalgesia (for discussion, see References 11 and 12).