in vesicles or released from them. However they can freely diffuse through cell membranes. In contrast to neurotransmitters, bioactive metabolites of fatty acids are often synthesized de novo or released from membrane bilayers upon cell stimulation [6]. Additionally unlike neurotransmitters there is a general lack of knowledge regarding their fate following the activation of receptors. The importance of several classes of bioactive lipid metabolites including those of arachidonic acid (AA) origin are now uncontested. The metabolism of free AA can result in several classes of lipid metabolites with opposing bioactivities. While the algogenic and pro-inflammatory prostanoids and leukotrienes drive and maintain inflammation the anti-inflammatory and analgesic EFAs reduce and resolve inflammation. Though the anti-inflammatory action of EFAs has been substantially studied, a number of more recent publications now indicate direct anti-nociceptive activity of these molecules. Thus, bioactive lipid metabolites have roles in the transmission of sensory information, specifically pain under pathological conditions. In most cases under physiological conditions the roles of these bioactive lipids are unclear. However upon the initiation of inflammation most algogenic lipids reduce the activation thresholds of pain specific neurons to stimuli, while others such as PGE2 can directly be painful. Although the pro-nociceptive roles of bioactive
