Elevation of intracellular Ca
2+
concentration induces the synthesis of N0
arachydonoylethanolamine (anandamide) in a sub0popu
lation of primary sensory
neurons. N0acylphosphatidylethanolamine phospholipa
se D (NAPE0PLD) is the only
known enzyme, which synthesises anandamide in a Ca
2+
0dependent manner. NAPE0
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 anandamide0hydrolysing
enzyme fatty acid amide
hydrolase (FAAH) are all expressed by sub0populatio
ns of nociceptive primary
sensory neurons. Thus, NAPE0PLD, TRPV1, the CB1 rec
eptor and FAAH could form
an autocrine signalling system, which could shape t
he activity of a major sub0
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 i
s known about NAPE0PLD
expression in primary sensory neurons under physiol
ogical and pathological
conditions. We report that NAPE0PLD 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 diff
ering but concerted changes in the
expression pattern of NAPE0PLD, the CB1 receptor, T
RPV1 and FAAH. Together
these data indicate the existence of the anatomical
basis for an autocrine signalling
system, in a major proportion of nociceptive primar
y sensory neurons, and that
alterations in that autocrine signalling by periphe
ral pathologies could contribute to
the development of both inflammatory and neuropathi
c pain.