Download Intra-articular injection of morphine: may it play a role? Serbülent

Intra-articular injection of
morphine: may it play a
role?
Serbülent Gökhan Beyaz, M.D.,
Associate Professor
Sakarya University Faculty of Medicine
Department of Anaesthesiology and Pain Medicine
Sakarya, Republic of Turkey
[email protected]
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Friedrich
Serturner
(1783-1841)
as a pharmacist’s
apprentice he was
the first person to
isolate morphine
from opium
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Morphine is highly potent opioid analgesic
drug and is principal active agent opium and
the prototype opiate.
Like other opioids, morphine acts directly on
the central nervous system (CNS) to relief
pain, and at synapses of the nucleus
accumbens in particular.
Morphine is highly addictive when compared
other substances, and tolerance and physical
and psychological dependents develop very
rapidly.
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How do opioid analgesic
work?
Morphine and endogenous opioids (the
enkephalins, dynorphins, and βendorphin) induce their biological effects
by interacting with three major classes
of receptors.
The 𝛅-, 𝜅-, and µ-opioid receptors
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There are some preferences for the
different endogenous opioid ligands for
the different receptors
β-endorphin for µ
enkephalins for 𝛅
dinorphins for 𝜅
Reisine T et al. Opioid and cannabioid receptors.Curr Opin Neu.
1994
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β-endorphin
It binds potently to both the 𝛅- and µ-receptors,
but has a relatively lower affinity for 𝜅-receptors,
suggesting that in peripheral tissues, where βendorphin is more abundant than enkephalins
or dinorphins, it may be an endogenous ligand
at the 𝛅- and µ-receptors.
Elvenes J et al. Expression of functional µ-receptors in
human osteoarthritic cartilage and chondrocytes. BBRC.
2003
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The three main types of opioid
receptors, µ, 𝜅, and 𝛅, belong to the
family of G protein-coupled receptors
inhibit adenylyl cyclase and hence
Childers S. Opioid receptor coupled
decrease the intracellular level of cyclic
second messenger systems, Lİfe Sci.
1991
AMP.
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Morphine
administration
Orally use in tablet but due to its poor
bioavailability, oral morphine is only oneeight of the potency parenteral morphine.
Parenterally as subcutaneous,
intravenous, or epidural injections.
Intraoperative applies (Periarticular use
and intraarticular use)
Chronic pain therapy (Intraarticular use)
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Opioids were believed to act solely on
the CNS, producing analgesia by
interaction with cerebral and spinal
opioid receptors.
This dogma was first challenged by
an experimental study that recorded
directly from the nasal mucosa the
local electrophysiological response to
painful stimulation of nasal
nociceptors.
Kobal G. Pain-related electrical potentials of the
human nasal mucosa elicited by chemical
stimulation. Pain 1985
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Peripheral opioid
analgesia
Local injection of opioids into
peripheral inflamed tissues caused
potent local naloxone-reversible
antinociception in laboratory animals
Stein et al., 1988, 1989; Levine and Taiwo, 1989;
Parsons et al., 1990; Kolesnikov et al., 1996; Perrot et
al., 1999
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The opioid-induced peripheral antinociception occurred preferentially in
inflamed tissue.
The number of opioid receptors in
peripheral tissue is normally low but
rapidly increases when inflation
comes into play.
Hassan et al., 1993; Schafer et al., 1995; Stein et
al.,1996
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The physiological importance of
peripheral opioid receptors was
doubted until in inflammatuar immune
cells were identified as the source of
endogenous opioid peptides. The
release of these endogenous ligands
allows for a communication between
immune cells and nociceptors.
Stein et al., 1995; Schafer et al., 1996, 1997; Machelska et al.,
1998, 2002; Rittner
et al., 2001
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Hydrophilic morphine metabolite, M6G significantly
reduces in inflammatory cutaneous hyperalgesia at
plasma concentrations that do not cause CNS
effects as confirmed by a lack of change of the
pupil size.
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0.5% Bupivacaine 200-400 mg
Morphine 5 mg
Epinephrine 300 µg
Metilprednisolon asetat 40 mg
Cephuroxime 750 mg
Totally SF 60 mL volum
Periarticular apply is
easy,
reduce opioid requirement,
improved patient satisfaction,
No infection risk.
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intraarticular of alone sufentanil is effective
intraarticular of sufentanil plus methylprednisolon is
more effective
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Results: significant joint damage occurred in mice
OA was induced by transection of the medial
before the onset of pain. To asses whether delayed
meniscotibial ligament. At various times post
pain was partly the result of increased endogenous
surgery, the opioid receptor antagonists naloxone
opioid function, naloxone or naloxone methiodide
or peripherally restricted naloxone methiodide were
was administered. Both opioid receptor antagonists
administered, and pain was assessed. Levels of the
led to pain onset 4 weeks earlier than in vehicleµ-opioid receptor were assessed in the nerves
treated mice, indicating a role of the peripheral
innervating the joint.
opioid system in masking OA pain.
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RCT
2 group, 2 phases
morphine 1 mg (total 2 mg during study)
Follow-up 9 days
Pain were assesment NRS, VAS and MPQ
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Our applies other intraarticular
techniques
Intra-articular drug injection
Intra-articular RFT
Genicular nerves RFT
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Genicular nerve of
traditional RFT or cooled
RFT
Target 1
Target 2
Target 3
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Genicular nerve of
traditional RFT or cooled
RFT
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Conclusion
Intra-articular opioid apply in intraoperative period is
useful,
Periarticular opioid apply in acute postoperative period
is useful,
The data of opioids for osteoarthritis knee pain
treatment is insufficient,
There are needs to long time RCT,
There are new therapy modalities in osteoarthritis knee
pain
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“Thank you for your attention.”
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