Introduction
Recent studies have demonstrated that opioid anal-
gesia cannot be exclusively attributed to effects within
the central nervous system. Peripheral opioid recep-
tors exist that can be activated by locally applied
opioid agonists and mediate analgesic effects that
are particularly prominent in painful inflammatory
conditions.
1–3
Their endogenous ligands, opioid pep-
tides, are expressed by resident immune cells in
inflamed tissues, and environmental stimuli or endo-
genous substances can stimulate the synthesis and
release of these opioid peptides that result in local
analgesia.
1
In addition, opioid receptor mRNA has
been detected in the cell bodies of small afferent fibers
in dorsal root ganglia,
4
and the three opioid recep-
tors, , and , are transported both peripherally
and centrally and are located on the peripheral and
spinal terminals of nociceptive C-fibers.
5
Morphine sulfate is a -opioid receptor agonist
and the endogenous ligand is -endorphin, which has
been shown to be released during environmental
stress and produce antinociception in rats.
6
In
man, intra-articular application of small, systemically
inactive doses of morphine during knee surgery
results in postoperative pain reduction.
7
Further,
inflamed synovial tissues contain the opioid peptides
-endorphin and met-enkephalin, and blockade
of intra-articular opioid receptors by the opiate
antagonist naloxone, which is particularly effective
on receptors, results in increased postoperative
pain.
8
It has also been shown that application of
the small-fiber excitant and inflammatory irritant
mustard oil (MO)
9,10
causes burning pain and activa-
tion of C-fibers in man
11
and enhances reflex
responses in flexor motorneurons.
12
MO injected into
the rat temporomandibular joint (TMJ) results in
nociceptive behaviors which can be reduced in a
dose-dependent manner by systemic morphine
administration,
13
an acute inflammatory response in
the tissues, a sustained and reversible increase
in excitability of nociceptive brain stem neurons in
trigeminal subnucleus caudalis, and a reflex activa-
tion of jaw-opening and jaw-closing muscles that is
dependent on the functional integrity of caudalis
14–17
(for review see Ref. 18). Since the role of peripheral
opioids in both acute inflammation and in reflex noci-
ceptive mechanisms in the trigeminal system is
unclear, the aim of the present study was to assess
the effects of morphine injection into the TMJ region
on the MO-induced reflex responses in jaw muscles.
Some of these data have been presented in abstract
form.
19
Materials and Methods
The study involved 39 male Sprague-Dawley rats
(260–360 g; Charles River, St-Constant, Quebec,
Somatosensory Systems, Pain
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0959-4965 © 1998 Lippincott Williams & Wilkins Vol 9 No 14 5 October 1998 3315
THIS study assessed the effect of peripherally applied
opioids on the electromyographic activity reflexly
evoked in digastric and masseter muscles by injection of
the small-fiber excitant and inflammatory irritant
mustard oil (MO) into the temporomandibular joint. In
39 anaesthetized rats, local pretreatment of joint tissues
with morphine (15 nmol) significantly depressed the jaw
muscle responses compared with saline, and the depres-
sion was antagonized by simultaneous local injection of
the opiate antagonist naloxone (2.7 nmol); systemic
morphine pretreatment (15 nmol, i.v.) did not influence
the muscle responses. The naloxone-reversible depression
of the MO-evoked muscle responses by local, but not
systemic morphine, supports the presence of peripheral
opioid receptors that may have a role in modulating
nociceptive responses. NeuroReport 9: 3315–3319 © 1998
Lippincott Williams & Wilkins.
Key words: Antinociceptive effects; Jaw muscle activity;
Morphine; Mustard oil; Naloxone; Peripheral opioid recep-
tors; Temporomandibular joint
Morphine application
to peripheral tissues
modulates nociceptive
jaw reflex
Merete Bakke,
CA
James W. Hu
1
and
Barry J. Sessle
1
Department of Oral Function and Physiology,
School of Dentistry, Faculty of Health Sciences,
University of Copenhagen, 20 Nørre Allé,
DK-2200 Copenhagen N, Denmark;
1
Department of Oral Physiology, Faculty of
Dentistry, University of Toronto, 124 Edward
Street, Toronto, Ontario M5G 1G6, Canada
CA
Corresponding Author
Website publication 16 October 1998 NeuroReport 9, 3315–3319 (1998)