Introduction

Fibromyalgia has been characterized as an ‘endocanna- binoid (eCB) deficiency syndrome’, along with other refractory maladies such as irritable bowel syndrome, migraine, premenstrual syndrome and other pain- processing disorders (Russo 2004). This syndrome may arise from diminished receptor expression, inadequate ligand biosynthesis or gain-of-function mutations in ligand-catabolizing enzymes. Helping you to understand these basic science concepts (and applying them) will be the goal of this chapter. Our trawl through basic science begins with definitions:

• Ligands are natural or synthetic compounds that bind to receptors.
• Ligands may activate receptors (‘agonists’) or deactivate receptors (‘inverse agonists’).
• Endogenous ligands (ligands produced by our own bodies) are synthesized by anabolic enzymes.
• To serve in self-regulatory roles, ligands must be broken down by catabolic enzymes.

Clinicians with a biomechanical or structural orien- tation may better understand the chemical concepts underlying eCB research by realizing that chemistry is structure (Ingber 1998). For example, the phar- macological principle of structure–activity relation- ships (SAR) is analogous to the anatomical concept of structure–function relationships.