Fig. 9. Speculative cartoon of nerve growth factor (NGF)–driven neuroimmune interactions and the putative action of cannabinoids. NGF sensitizes primary afferent neurones and releases many inflammatory mediators, including leukotriene B⁴(LTB⁴) and more NGF. LTB⁴mediates the neutrophil influx that is responsible for hyperalgesia. Hydroperoxyeicosatetraenoic acids (HPETEs) by means of action on the vanilloid TRPV1 receptor (previously VR1) may provide the link between neutrophils and hyperalgesia. Anandamide (AEA) acts neuronally on CB¹receptors to quell primary afferent excitability. Putative sites of action of the reduction in neutrophil influx by palmitoylethanolamide (PEA) are shown, although a nonperipheral site of action cannot be discounted.