Transcript RNA interference as a resistance mechanism against crop parasites

Understanding pathophysiology
and patho biochemistry of disc
disease and radiculopathy
and monitoring of sciatica
Satishchandra gore
GORE SYSTEM
www.drgoreonline.com
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Present day acts of omission
1. History listen
2. Dermatomes
3. Palpation
4. Mackenzie’s test
5. Discography
6. Staging of sciatica
7. Sub sets of sciatica
8. Detect Confirm and monitor sciatica
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PM R. 2011 Jun;3(6 Suppl 1):S12-7.
Identifying inflammatory targets for biologic therapies for spine pain.
Jacobs LJ1, Vo N, Kang JD.
• Costs -spine-related conditions- enormous - trending
upward.
• Current methods employed to treat inflammatorymediated pain are targeted at alleviating symptoms,
rather than correcting the underlying cause of disease.
• Biologic therapies that address the underlying cause of
pain could potentially decrease the costs associated with
treating spine pathology.
• Biochemical basis for inflammatory-mediated
intervertebral disk, facet joint, and nerve pain exists.
• With rapid advances in biomedical technology, these
interventions may be available for clinical use in the near
future.
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S. Rajasekaran , K. Venkatadass, J. Naresh Babu , K. Ganesh, Ajoy P. Shetty
Pharmacological enhancement of disc diffusion and differentiation of healthy, ageing and degenerated
discs Results from in-vivo serial post-contrast MRI studies in 365 human lumbar discs .
Eur Spine J (2008) 17:626–643
• Irrespective of age of patient
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•
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‘Healthy discs’ structurally intact and functionally
normal. Normal normal.
‘Ageing discs’ structurally intact but with reduced
diffusion. There is generally lack of distinction or a
cleavage plane between nucleus and annulus.
‘Degenerated discs’ structural failure and abnormal
diffusion.
• Commonest early structural failure is an Annular
tear. Late structural failure can be progressive
derangement of the nucleus and annulus.
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What makes pain “visible” :
nerve supply
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Intervertebral disc, sensory nerves and neurotrophins: who is who in discogenic pain?
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Nat Rev Rheumatol. 2014 Jan;10(1):44-56. Epub 2013 Oct 29.
Role of cytokines in intervertebral disc degeneration: pain and disc content.
Risbud MV, Shapiro IM.
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Degeneration of the intervertebral discs (IVDs) is a major contributor to back, neck
and radicular pain.
•
IVD degeneration is characterized by increases in levels of the proinflammatory
cytokines TNF, IL-1α, IL-1β, IL-6 and IL-17 secreted by the IVD cells
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imbalance in catabolic and anabolic responses --degeneration of IVD tissuesherniation and radicular pain.
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chemokines from degenerating discs- infiltration and activation of immune cellsamplifying the inflammatory cascade. Leukocyte migration into the IVD is
accompanied by the appearance of microvasculature tissue and nerve fibres.
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Furthermore, neurogenic factors, generated by both disc and immune cells, induce
expression of pain-associated cation channels in the dorsal root ganglion.
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Depolarization of these ion channels is likely to promote discogenic and radicular
pain, and reinforce the cytokine-mediated degenerative cascade.
•
Taken together, an enhanced understanding of the contribution of cytokines and
immune cells to these catabolic, angiogenic and nociceptive processes could provide
new targets for the treatment of symptomatic disc disease.
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Clin Biomech (Bristol, Avon). 2010 Dec;25(10):961-71
Healing of a painful intervertebral disc should not be confused with reversing
disc degeneration: implications for physical therapies for discogenic back pain.
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Intervertebral discs deteriorate over many years, from the nucleus
outwards, to an extent that is influenced by genetic inheritance and
metabolite transport.
•
Degeneration is often painful because nerves in the peripheral anulus
or vertebral endplate can be sensitised by inflammatory-like changes
arising from contact with blood or displaced nucleus pulposus.
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Surgically-removed human discs show an active inflammatory
process proceeding from the outside-in, and animal studies confirm
that effective healing occurs only in the outer anulus and endplate,
where cell density and metabolite transport are greatest.
•
Healing of the disc periphery has the potential to relieve discogenic
pain, by re-establishing a physical barrier between nucleus pulposus
and nerves, and reducing inflammation.
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Disc Fx modality of disc repair
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Pain Physician. 2007 Jan;10(1):147-64.
Systematic review of discography as a diagnostic test for spinal pain: an update.
Buenaventura RM1, Shah RV, Patel V, Benyamin R, Singh V.
There is strong evidence supporting the role of
discography in identifying that subset of patients
with lumbar discogenic pain , moderate in
cervical discogenic pain and limited in thoracic
discogenic pain.
Discography is a useful imaging and pain
evaluation tool in identifying a subset of patients
with chronic spinal pain secondary to
intervertebral disc disorders.
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In vivo visualization paradigm
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Nucleus and its effects
Effects of nucleus pulposus on nerve root neural activity, mechanosensitivity,
axonal morphology, and sodium channel expression.
Chen C, Cavanaugh JM, Song Z, Takebayashi T, Kallakuri S, Wooley PH.
Spine (Phila Pa 1976). 2004 Jan 1;29(1):17-25.
Effect of nucleus pulposus on the neural activity of dorsal root ganglion.
Takebayashi T, Cavanaugh JM, Cüneyt Ozaktay A, Kallakuri S, Chen C.
Spine (Phila Pa 1976). 2001 Apr 15;26(8):940-5.
Application of nucleus pulposus to the nerve root simultaneously reduces blood
flow in dorsal root ganglion and corresponding hindpaw in the rat.
Yabuki S, Igarashi T, Kikuchi S.
Spine (Phila Pa 1976). 2000 Jun 15;25(12):1471-6.
Acute effects of nucleus pulposus on blood flow and endoneurial fluid pressure
in rat dorsal root ganglia.
Yabuki S, Kikuchi S, Olmarker K, Myers RR.
Spine (Phila Pa 1976). 1998 Dec 1;23(23):2517-23.
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Prevention of compartment syndrome in dorsal root ganglia caused by exposure to
nucleus pulposus.
Yabuki S, Onda A, Kikuchi S, Myers RR.
Spine (Phila Pa 1976). 2001 Apr 15;26(8):870-5.
Chronic effects of the nucleus pulposus applied to nerve roots on ectopic firing and
conduction velocity.
Ozawa K, Atsuta Y, Kato T.
Spine (Phila Pa 1976). 2001 Dec 15;26(24):2661-5.
Epidural application of nucleus pulposus enhances nociresponses of rat dorsal horn
neurons.
Anzai H, Hamba M, Onda A, Konno S, Kikuchi S.
Spine (Phila Pa 1976). 2002 Feb 1;27(3):E50-5.
Up-regulation of acid-sensing ion channel 3 in dorsal root ganglion neurons following
application of nucleus pulposus on nerve root in rats.
Ohtori S, Inoue G, Koshi T, Ito T, Doya H, Saito T, Moriya H, Takahashi K.
Spine (Phila Pa 1976). 2006 Aug 15;31(18):2048-52.
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Outcome of discogenic sciatica
& Pain generators
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Back pain presentation axial
Axial back pain
Horizontal or vertical
Associated spasm
Posture induced changes in pain
Assessing root mobility , where root is sensitised!!
Examination in standing and lying down
Static examination can not bring out dynamic complaints
Dynamic in time and location
Red flags: unrelenting , pain at night
Investigations need and interpretation
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Back pain targets I
Annular tear central non healing
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Paraspinal back pain: MB of DR
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II
Facet bilateral two level for MB of DR
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Conservatively treated massive prolapsed discs: a 7-year follow-up.
Benson RT, Tavares SP, Robertson SC, Sharp R, Marshall RW.
Ann R Coll Surg Engl. 2010 Mar;92(2):147-53
A massive disc herniation can pursue a favourable
clinical course. If early progress is shown, the
long-term prognosis is very good and even
massive disc herniations can be treated
conservatively.
Who will show the progress?
How will it be shown?
Unanswered questions!!!
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Leg pain 6 questions
L5
S1
knee
Is pain along dermatomes?
If yes which root?
Is it disc?
If yes which disc?
Non invasive imaging
Invasive imaging
Answering:
Where is pain coming from?
Why is it persisting?
calf
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CENTRALISATION
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Limitations of dermatomes:
old unreliable dogma etc.
Can be OVERCOME: PALPATE
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Limitations of “mute” imaging
Image symptom paradox
30% either way
Images look same but presentations are different
How to overcome this uncertainty
Deciphering images with added knowledge from
our studies. See <- Visualize
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Mechanism of sciatica
Effects of nucleus pulposus on nerve root
activity,
mechanosensitivity,
axonal
morphology, sodium channel expression:
Chen et al: spine 2004 29:1:17-25
Seven days' exposure of nerve root to nucleus pulposus
potential neural conduction block +++ higher intensity
of ectopic discharges on compression due to mechanical
sensitization of nerve root.
whereas 42 days' exposure resulted in desensitization.
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Sciatica
Mechano sensitized root : SNRB and PALPATE
for gore sign …
L5
s1
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PALPATE elicit tenderness AND BLOCK LTDPN at sinus tarsi for L5 or sural for S1 sciatica pain
L5
S1
L5
Accepted for publication in IJASS july 2014 special miss spine surgery issue Gore and Nadkarni
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Change from image and dermatome paradigm to NERVE paradigm : PALPATE
Staging of sciatica 3 stages progressive, may jump.
Stage 1 of mechano [pressure] sensitization 80% outpatient
Stage 2 of mechanical compression 15 % SLR
Stage 3 of nerve dysfunction 5% standard neuroexamination
limitation of Root mobility
Indicates stretch
sensitivity
**May improve if it is only
Inflammatory
And
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Not mechanical
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2 sub sets
LATERAL Knee pain: BE AWARE
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Heel pain: ouch after zzz
Maximum in morning
There is no way
bone grows
to cause pain!!
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