Inflammation of peripheral tissues and injury to peripheral nerves induce diferring effects in the expression of the calcium-sensitive anandamide-synthesising enzyme and related molecules in rat primary sensory neurons

Elevation of intracellular Ca2+ concentration induces the synthesis of N-arachydonoylethanolamine (anandamide) in a sub-population of primary sensory neurons. N-acylphosphatidylethanolamine phospholipase D (NAPE-PLD) is the only known enzyme, which synthesises anandamide in a Ca2+ -dependent manner. NAPE-PLD mRNA, as well as anandamide's main targets, the excitatory transient receptor potential vanilloid type 1 ion channel (TRPV1) and the inhibitory cannabinoid type 1 (CB1) receptor and the main anandamide-hydrolysing enzyme fatty acid amide hydrolase (FAAH) are all expressed by sub-populations of nociceptive primary sensory neurons. Thus, NAPE-PLD, TRPV1, the CB1 receptor and FAAH could form an autocrine signalling system, which could shape the activity of a major sub-population of nociceptive primary sensory neurons, hence contribute to the development of pain. While the expression patterns of TRPV1, the CB1 receptor and FAAH have been comprehensively elucidated, little is known about NAPE-PLD expression in primary sensory neurons under physiological and pathological conditions. We report that NAPE-PLD is expressed by about a third of primary sensory neurons, the overwhelming majority of which also express nociceptive markers as well as the CB1 receptor, TRPV1 and FAAH. Inflammation of peripheral tissues and injury to peripheral nerves induce differing but concerted changes in the expression pattern of NAPE-PLD, the CB1 receptor, TRPV1 and FAAH. Together these data indicate the existence of the anatomical basis for an autocrine signalling system, in a major proportion of nociceptive primary sensory neurons, and that alterations in that autocrine signalling by peripheral pathologies could contribute to the development of both inflammatory and neuropathic pain. This article is protected by copyright. All rights reserved