Title: Glukokortikoid vid behandling av k
1Glukokortikoid vid behandling av käkledssjukdomar
- Finns koppling till serotonin?
Lars Fredriksson
2- Anti-inflammatory actions of glucocorticoids
Barnes PJ. 1998 - Short-term effects of intra-articular sodium
hyaluronate, glucocorticoid, and saline
injections on rheumatoid arthritis of the
temporomandibular joint Kopp S, Akerman S,
Nilner M. 1991 - Pain and synovial fluid concentration of
serotonin in arthritic temporomandibular joints.
Alstergren P, Kopp S. 1997 - Immediate effects of the serotonin antagonist
granisetron on temporomandibular joint pain in
patients with systemic inflammatory disorders.
Voog O, Alstergren P, Leibur E, Kallikorm R, Kopp
S. 2000
31
Anti-inflammatory actions of glucocorticoids
Barnes PJ. 1998
- GC are widely used for the suppression of
inflammation in chronic inflammatory diseases
such as asthma, RA, inflammatory bowel disease
and autoimmune diseases, all with increased
expression of inflammatory genes.
4 Anti-inflammatory actions of glucocorticoids
Barnes PJ. 1998
- GC bind to GC-receptors in the cytoplasm which
then dimerize and translocate to the nucleus,
where they bind to GC response elements (GRE) on
GC-responsive genes, resulting in increased
transcription for genes coding for
anti-inflammatory proteins
5GC-receptor (GR)
6- GCS bind to GR in the cytoplasm which then
dimerize and translocate to the nucleus, where
they bind to GC response elements (GRE) on
GC-responsive genes, resulting in increased
transcription for genes coding for
anti-inflammatory proteins
7560-561
81
Anti-inflammatory actions of glucocorticoids
Barnes PJ. 1998
- GC inhibit the expression of multiple
inflammatory genes
9(No Transcript)
101
Anti-inflammatory actions of glucocorticoids
Barnes PJ. 1998
- GC appear to inhibit cytokine gene expression by
inhibiting transcription factors that regulate
their expression, rather than by binding to their
promotor regions.
111
Anti-inflammatory actions of glucocorticoids
Barnes PJ. 1998
- GC decrease the transcription of genes coding for
certain receptors that are involved in the
inflammatory process.
12GC increase the syntesis of lipocortin-1, that
has inhibitory effect on phospholipas A2 and
therefore inhibit the production of lipid
mediators as well as inhbit genes coding for
COX-2.
131
Anti-inflammatory actions of glucocorticoids
Barnes PJ. 1998
- GC reduce the survival of eosinophils and
T-lymfocytes, since eosinophils are dependent of
IL-5 and GM-CSF which are blocked by GC which
leads to apoptosis of eosinophils and
T-lymfocytes.
141
Anti-inflammatory actions of glucocorticoids
Barnes PJ. 1998
- Adhesion molecules play a key role in trafficking
of inflammatory cells to the sites of
inflammation. The expression of many adhesion
molecules on endothelial cells is induced by
cytokines and GC may indirectly to a reduced
expression via their inhibitory effects on
cytokines such as IL-1beta and TNF-alfa.
151
Anti-inflammatory actions of glucocorticoids
Barnes PJ. 1998
- Inhaled GC reduce the secretion of chemokines and
pro-inflammatory cytokines from alveolar
macrophages in patients with asthma. Oral
prednisolone inhibits the increased gene
expression of IL-Ibeta.
161
Anti-inflammatory actions of glucocorticoids
Barnes PJ. 1998
- Systemic GC increase pheripheral neutrophil
counts, which may reflect the increased survival
time due to an inhibitory action of neutrofil
apoptosis.
171
Anti-inflammatory actions of glucocorticoids
Barnes PJ. 1998
- GC inhibit the increased transcription of the
IL-8 gene induced by TNF-alfa in cultured human
airway epithelial cells in vitro. - GC decrease the transcription of inflammatory
proteins including iNOS, COX-2, cPLA2 and
endothelin-1.
181
Anti-inflammatory actions of glucocorticoids
Barnes PJ. 1998
- GC do not appear to have a direct inhibitory
effect on mediator release from mastcells.
191
Anti-inflammatory actions of glucocorticoids
Barnes PJ. 1998
- GC may inhibit several aspects of neurogenic
inflammation including the synthesis of
tachykinins by repression of the
preprotachykinin-A gene, reduced expression of
tachykinin receptors and by increasing expression
of neural endopeptidase which degrades
tachykinins.
201
Anti-inflammatory actions of glucocorticoids
Barnes PJ. 1998
- Rarely patients with chronic inflammatory
diseases fail to respond to GC but there are
however patients with GC resistance.
212
Short-term effects of intra-articular sodium
hyaluronate, glucocorticoid, and saline
injections on rheumatoid arthritis of the
temporomandibular joint Kopp S, Akerman S,
Nilner M. 1991
AIM To investigate the short-term subjective and
clinical effects of sodium hyaluronate on TMJ
arthritis in individuals with RA and to compare
these effects with those of glucocorticoid and
saline. M and M Forty-one patients with RA.
Three groups HA gruop n14, CO group n14, SA
group n13. RESULTS After treatment Fig 1. 75
of the patients in the CO group were much
improved or symptom free. Subjective symptoms
(VAS) decreased with 34 mm in the CO group. Pain
at rest was significantly lower in the CO
group. Tenderness to digital palpation of the
lateral and posterior aspect were significantly
eliminated or reduced in the CO group. The
maximum voluntary moth opening was increased by 6
mm in the CO group.
222
Short-term effects of intra-articular sodium
hyaluronate, glucocorticoid, and saline
injections on rheumatoid arthritis of the
temporomandibular joint Kopp S, Akerman S,
Nilner M. 1991
Conclusion Sodium hyaluronate has a benefical
effect on subjective symptoms as well as clinical
signs of TMJ arthritis in patients with chronic
RA, although not as good as that of
glucocorticoids.
233
Pain and synovial fluid concentration of
serotonin in arthritic temporomandibular joints.
Alstergren P, Kopp S. 1997
AIM To investigate the relation between 5-HT in
the synovial fluid and pain of arthritic TM
joints. M and M Eleven patients with chronic
inflammatory joint disease. One male and 10
females (22 joints). RESULTS After treatment PM
was positively correlated to SF-5-HT on the
corresponding side (r 0.51, P 0.014, n 22)
Fig 1. The maximum voluntary mouth opening
capacity was negatively correlated to the
SF-5-HTSum when the influence of S-5-HT was
acconted for (rP -0.73, P 0.012, n 11) .
243
Pain and synovial fluid concentration of
serotonin in arthritic temporomandibular joints.
Alstergren P, Kopp S. 1997
Conclusion 5-HT in the TMJ synovial fluid is
associated with pain perceived upon movement of
the joint and to decreased mandibular mobility
254
Immediate effects of the serotonin antagonist
granisetron on temporomandibular joint pain in
patients with systemic inflammatory disorders.
Voog O, Alstergren P, Leibur E, Kallikorm R, Kopp
S. 2000
AIM To investigate if the 5-HT3 receptor
antagonist granisetron reduces TMJ pain in
patients with systemic inflammatory joint
disease. M and M Sixteen patients with chronic
inflammatory joint disease. Four males and 12
females. Table 1. RESULTS After treatment with
granisetron Granisetron group VASRest was
decreased 10 minutes after i.a. injection of
granisetron (p 0.028) but not after 20 minutes
(Fig. 1). VASMVM was decreased after 20 minutes
(p 0.002), but not after the first 10 minutes
(Fig.2). PPT was increased after 20 minutes (p
0.036). Difference between groups VASRest before
injection was similar in both groups. The
patients in the granisetron group had
signoficantly lower VASRest than the patients in
the saline group 10 minutes after injection (p
0.033 Fig. 1).
264
Immediate effects of the serotonin antagonist
granisetron on temporomandibular joint pain in
patients with systemic inflammatory disorders.
Voog O, Alstergren P, Leibur E, Kallikorm R, Kopp
S. 2000
Conclusion Granisetron has an immediate,
shortlasting and specific pain reducing effect in
TMJ inflammatory arthritis. The 5-HT3 receptor
may therefore be involved in the mediation of TMJ
pain in systemic inflammatory joint disorders.
27Serotonergic mechanisms influence the response to
glucocorticoid treatment in TMJ arthritis Lars
Fredriksson, DDS, PhD Student, Per Alstergren
DDS, PhD, Associate Professor, Sigvard Kopp, DDS,
PhD, Professor and Chairman
28AIM
- To investigate the influence of synovial fluid
and blood levels of 5-HT on the effects by
intra-articular injections of glucocorticoid on
pain and allodynia of the TMJ in patients with
chronic and systemic inflammatory disorders of
the TMJ.
29Materials and Methods
- One male and nineteen female patients with
inflammatory TMJ disorders participated (Table
1).
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31Results
- Treatment effect
- Table 2 shows the pretreatment and follow-up
values of the clinical variables and synovial
fluid levels of 5-HT.
32Table 2
331A
Change in temporomandibular joint (TMJ) resting
pain intensity (A) after intra-articular
glucocorticoid treatment in 9 patients with
undetectable and 11 patients with detectable
pretreatment levels of serotonin (5-HT) in the
TMJ synovial fluid and chronic inflammatory joint
disease. There was a negative correlation between
5-HT and change in resting pain after treatment
(rs -0.52, n 20, p 0.018).
341B
Change in TMJ pain intensity on mouth opening (B)
in 8 patients with undetectable and 5 patients
with detectable pretreatment levels of 5-HT in
TMJ synovial fluid and chronic inflammatory joint
disease. There was a negative correlation between
5-HT and change in pain intensity on mouth
opening after treatment (rs -0.57, n 13, p
0.041).
352A
Pretreatment plasma levels of serotonin (5-HT) in
patients with chronic inflammatory joint disease,
7 with a decrease and 3 with an increase of
temporomandibular joint (TMJ) resting pain
intensity (A) after intra-articular
glucocorticoid treatment. There was a positive
correlation between 5-HT and change in resting
pain intensity after treatment (rs 0.66, n
10, p 0.040).
362B
Pretreatment plasma level of 5-HT in 5 patients
with a decrease and 5 patients with an increase
of TMJ pressure-pain threshold (B) after this
treatment. There was a positive correlation
between 5-HT and change in pressure-pain
threshold after treatment (rs 0.83, n 10, p
0.003).
37Conclusions
- This study shows that local and systemic
serotonergic mechanisms partly determine the
effect of intra-articular glucocorticoid
treatment on TMJ pain in patients with chronic
TMJ arthritis of systemic nature, while change in
pressure pain threshold over the TMJ are
influenced by systemic serotonergic mechanisms.