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VOL. 75 (3), 389-418, 2009 CENTRAL AND PERIPHERAL ENDOGENOUS MORPHINE

ing with the cell bodies of Purkinje cells (Figures 5B and C) which
are reported as expressing µ receptors (83, 84).

Morphine in the nervous system

Various studies have pointed to the involvement of endogenous
morphine in analgesia, memory, plasticity and development, as well
as in the installation of addiction. A number of studies have described
the effects of exogenous morphine in the CNS although, without an
understanding of effective concentrations inside the synaptic cleft, it
is difficult to speculate about the functions of endogenous morphine
by extrapolating from results obtained with exogenous morphine. It
is also likely that the level of endogenous morphine being produced
and secreted varies with physiological conditions (notably stress). It
is important to note that the concentrations used in most experiments
(therapeutic doses) are often greater than 1 µM. Nevertheless, on the
basis of the observed effects of exogenous morphine coupled with
an understanding of the distribution of endogenous morphine and
its receptors in the CNS, hypotheses can be formulated about the
physiological roles of endogenous morphine.

Endogenous morphine and nociception

An experiment conducted in the year 2000 showed that
endogenous morphine colocalises with µ receptors in various parts
of the brain stem. These include the locus coeruleus, the parabrachial
nucleus, the periaqueductal grey substance and the nucleus raphe,
all structures known to be involved in supraspinal nociception
modulation (1). On the other hand, experiments carried out by
Guarna et al. showed that the injection of antibodies directed against
morphine into murine CSF (a procedure which lowers the level
of endogenous morphine in the brain) induced hypersensitivity to
heat-associated pain (85). Moreover, knockout mice which do not
express µ receptors are abnormally sensitive to thermal stimuli but
not to mechanical stimuli (86). These findings seem to suggest that
endogenous morphine mainly modulates sensitivity to thermal pain.

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