ABSTRACT
Neuropathic pain may occur from numerous situations such as accidental nerve trauma, cancer chemotherapy, diabetes, and so on. These conditions involve varying anatomic sites and therefore require various treatment approaches. In this section we discuss the testing of agonist drug combinations and the analysis of data from these tests that may provide effective treatments. Our interest is in agonist drugs that are overtly similar in that they produce the same effect. In most cases these are agents that work through different mechanisms. It is well known that the treatment of neuropathic pain is dif•cult and the proper drug combination for any patient is often determined empirically (Fields et al., 1999). The main focus in this chapter is the experimental design and associated data analysis to assess whether certain drug combinations produce effects that differ from the expected effects, that is, is there synergism? Our main application, which follows from the theory, is drawn from a preclinical pain model in rodents. The drugs we discuss here to illustrate the methodology and analysis include tramadol, a mu opioid with concomitant action of blocking serotonin and norepinephrine (Codd et al., 1995), and one or more anticonvulsant
9.1 Introduction .................................................................................................. 169 9.2 Dose-Effect Analysis .................................................................................... 170 9.3 Isoboles ......................................................................................................... 172 9.4 Application: Testing Drugs for Neuropathic Pain ........................................ 174 9.5 Curved Isoboles ............................................................................................ 176 9.6 Analysis on the Effect Scale ......................................................................... 178 9.7 Conclusion .................................................................................................... 179 References .............................................................................................................. 180
agents since these agents have been shown to have ef•cacy in relieving neuropathic pain (Blackburn-Munro and Erichsen, 2005). However, the methodology presented here is broadly applicable. Our aim is a demonstration of the mathematical theory that underlies this approach and its use in guiding combination drug testing.
