ansiktssmerter
TRANSCRIPT
![Page 2: Ansiktssmerter](https://reader035.vdocuments.mx/reader035/viewer/2022062514/55842a21d8b42a86478b4edd/html5/thumbnails/2.jpg)
2
Which specialist should treat facial pain?
Challenge to medical and dental professions….
The patients have multiple diagnoses, requiring management by multiple disciplines Neurology Otolaryngology Dentistry Psychiatry
![Page 3: Ansiktssmerter](https://reader035.vdocuments.mx/reader035/viewer/2022062514/55842a21d8b42a86478b4edd/html5/thumbnails/3.jpg)
3
Differential diagnosis
Atypical facial pain
Trigeminal neuralgia (primary or secondary?)
Horton's syndrome (cluster headache)
Temporomandibular disorders
Dental pain
Sinusitis
Cancer
Cervical pain
Myofascial pain
![Page 4: Ansiktssmerter](https://reader035.vdocuments.mx/reader035/viewer/2022062514/55842a21d8b42a86478b4edd/html5/thumbnails/4.jpg)
4
Dental pain
![Page 5: Ansiktssmerter](https://reader035.vdocuments.mx/reader035/viewer/2022062514/55842a21d8b42a86478b4edd/html5/thumbnails/5.jpg)
5
Atypical odontalgia--a form of neuropathic pain that emulates dental pain
Overtreatment - numerous invasive procedures and unnecessary treatment.
Dental extraction, injection or even the placement of a crown represents a tissue trauma and deafferentation.
A small percentage have a genetic predisposition to deafferentation pain.
![Page 6: Ansiktssmerter](https://reader035.vdocuments.mx/reader035/viewer/2022062514/55842a21d8b42a86478b4edd/html5/thumbnails/6.jpg)
6
Oral and maxillofacial surgery in patients with chronic orofacial pain. Pupulation: 120 patients
Diagnoses: myofascial pain (50%) atypical facial neuralgia (40%), depression (30%) TMJ synovitis (14%) TMJ osteoarthritis (12%) trigeminal neuralgia (10%) TMJ fibrosis (2%)
History of previous oral and maxillofacial surgical procedures (32%).
Israel HA 2003
![Page 7: Ansiktssmerter](https://reader035.vdocuments.mx/reader035/viewer/2022062514/55842a21d8b42a86478b4edd/html5/thumbnails/7.jpg)
7
Oral and maxillofacial surgery in patients with chronic orofacial pain.
Procedures performed
endodontics (30%) extractions (27%), apicoectomies (12%) temporomandibular joint (TMJ) surgery (6%), neurolysis (5%) orthognathic surgery (3%) debridement of bone cavities (2%)
Surgery exacerbated pain in 55% of those operated
Israel HA 2003
![Page 8: Ansiktssmerter](https://reader035.vdocuments.mx/reader035/viewer/2022062514/55842a21d8b42a86478b4edd/html5/thumbnails/8.jpg)
8
Oral and maxillofacial surgery in patients with chronic orofacial pain
Treatment recommendations: medications (91%): TCA, anticonculsants, opioids? physical therapy (36%) psychiatric management (30%) trigger injections (15%) oral appliances (13%) (local anesthesia, capsaicain) biofeedback (13%) acupuncture (8%) TENS? surgery (4%) Botox injections (1%)
Israel HA 2003
![Page 9: Ansiktssmerter](https://reader035.vdocuments.mx/reader035/viewer/2022062514/55842a21d8b42a86478b4edd/html5/thumbnails/9.jpg)
9
Oral and maxillofacial surgery in patients with chronic orofacial pain
Misdiagnosis and multiple failed treatments were common, and lead to sequelae, with delay of necessary treatment in 5%
Surgery, may exacerbate the pain,
Surgery must be based on a specific diagnosis that is amenable to surgical therapy
Israel HA 2003
![Page 10: Ansiktssmerter](https://reader035.vdocuments.mx/reader035/viewer/2022062514/55842a21d8b42a86478b4edd/html5/thumbnails/10.jpg)
10
What is neuropathic pain (NP)?
Neuropathic pain initiated by a lesion or disease affecting parts of the nervous system that normally transmits pain related signals
![Page 11: Ansiktssmerter](https://reader035.vdocuments.mx/reader035/viewer/2022062514/55842a21d8b42a86478b4edd/html5/thumbnails/11.jpg)
11
Some characteristics of NP:
The symptoms: Both stimulus independent and stimulus dependent pain A delayed onset, but remain after healing My change over time
Heterogeneous mechanisms not explained by a single etiology or a specific lesion
Difficult to treat, limited effect of TCA, anticonvulsants and opioids.
![Page 12: Ansiktssmerter](https://reader035.vdocuments.mx/reader035/viewer/2022062514/55842a21d8b42a86478b4edd/html5/thumbnails/12.jpg)
12
From simple sensory testing to Quantitative sensory testing (QST ) Touch and Pin prik Cold/heat Pressure and vibration
Thermorollers (200C and 450C)
Von Frey hairs (standardized mechanical stimuli)
Hypo-/hyper- phenomena?
Temporal summation (response to repeated stimulation
Thermorollers
”Von Frey hair” – Nylon filaments
![Page 13: Ansiktssmerter](https://reader035.vdocuments.mx/reader035/viewer/2022062514/55842a21d8b42a86478b4edd/html5/thumbnails/13.jpg)
13
Thermo test
Heat pain tolerance Heat pain
Neutral
Cold
Cold pain
Heat
Patients respond to standardized thermal stimuli
![Page 14: Ansiktssmerter](https://reader035.vdocuments.mx/reader035/viewer/2022062514/55842a21d8b42a86478b4edd/html5/thumbnails/14.jpg)
14
Diagnostic dilemma:
A specific symptom can reflect different pathophysiological mechanisms
To predict the underlying mechanism, we need a wider symptom profile and a battery of sensory stimuli.
![Page 15: Ansiktssmerter](https://reader035.vdocuments.mx/reader035/viewer/2022062514/55842a21d8b42a86478b4edd/html5/thumbnails/15.jpg)
15
Phenotypic mapping:
Standardised QST protocol to determine the mechanisms and design a mechanism-based treatment
German Research Network on Neuropathic Pain, Baron R 2006
![Page 16: Ansiktssmerter](https://reader035.vdocuments.mx/reader035/viewer/2022062514/55842a21d8b42a86478b4edd/html5/thumbnails/16.jpg)
16
A standardized mapping of symptoms and signs
- to determine the mechanisms (target)
- to optimize therapy
Baron R. Mechanisms of Disease ..Nat Clin Pract Neurol 2006
![Page 17: Ansiktssmerter](https://reader035.vdocuments.mx/reader035/viewer/2022062514/55842a21d8b42a86478b4edd/html5/thumbnails/17.jpg)
17
Neuropathic pain based on
complex mechanisms!
Central and peripheral mechanisms
![Page 18: Ansiktssmerter](https://reader035.vdocuments.mx/reader035/viewer/2022062514/55842a21d8b42a86478b4edd/html5/thumbnails/18.jpg)
18
Animal pain research- nerve injury models provide new
insight to the mechanisms
![Page 19: Ansiktssmerter](https://reader035.vdocuments.mx/reader035/viewer/2022062514/55842a21d8b42a86478b4edd/html5/thumbnails/19.jpg)
19
Mechanisms after a nerve injury:
Peripherally Nerve sprouting and neuroma
DRG:
Sprouting of sympathetic fibres
Increased gene expression of ion-channels, transmittors and receptors
. Decreased expression of opioid
receptors.
Dorsal horn Loss of inhibitory (GABA)
interneurons (apoptosis)
Impaired central inhibition and increased central fascilitation
![Page 20: Ansiktssmerter](https://reader035.vdocuments.mx/reader035/viewer/2022062514/55842a21d8b42a86478b4edd/html5/thumbnails/20.jpg)
20
![Page 21: Ansiktssmerter](https://reader035.vdocuments.mx/reader035/viewer/2022062514/55842a21d8b42a86478b4edd/html5/thumbnails/21.jpg)
21
New insight:
Decreased function of unmyelinated fibres Downregulation of:
Nav1.8 channels Bradykinin- (B2), substance P- and opioid- receptors
Increased function of myelinated fibres Upregulation of:
Ca α2δ-1 channel subunits (gabapentin?) Na 1.3 channels Bradykinin (BK B1) and capsaicin (TRPV1) receptors
Future therapy: Specific sodium channel blockers?
![Page 22: Ansiktssmerter](https://reader035.vdocuments.mx/reader035/viewer/2022062514/55842a21d8b42a86478b4edd/html5/thumbnails/22.jpg)
22
Ion channels and receptors are translocated to intact neurons Na channels TRPV1 (vanilloid) adrenoceptors
Baron R 2006
![Page 23: Ansiktssmerter](https://reader035.vdocuments.mx/reader035/viewer/2022062514/55842a21d8b42a86478b4edd/html5/thumbnails/23.jpg)
23
Lysophosphatidic acid (LPA)
A small phospholipid
After tissue and nerve injury release from activated platelets, damaged nerve cells (cancer cells)
LPA activate LPA receptors (DRG) leading to demyelinisation and allodynia
In knockout mice (no LPA1 reseptor) or after pretreatment with ”antidot” (AS ODN) no demyelinisation or allodynia
![Page 24: Ansiktssmerter](https://reader035.vdocuments.mx/reader035/viewer/2022062514/55842a21d8b42a86478b4edd/html5/thumbnails/24.jpg)
24
![Page 25: Ansiktssmerter](https://reader035.vdocuments.mx/reader035/viewer/2022062514/55842a21d8b42a86478b4edd/html5/thumbnails/25.jpg)
25
Evidence for activated glia
cells
Astrocytes in spinal cord activated after sciatic nerve damage
Garrison et al 1991
![Page 26: Ansiktssmerter](https://reader035.vdocuments.mx/reader035/viewer/2022062514/55842a21d8b42a86478b4edd/html5/thumbnails/26.jpg)
26
A close interplay
Glutamate
![Page 27: Ansiktssmerter](https://reader035.vdocuments.mx/reader035/viewer/2022062514/55842a21d8b42a86478b4edd/html5/thumbnails/27.jpg)
27 Marchand F et al Nature 2005
![Page 28: Ansiktssmerter](https://reader035.vdocuments.mx/reader035/viewer/2022062514/55842a21d8b42a86478b4edd/html5/thumbnails/28.jpg)
28
Are the activated glica cells neurodestructive?
Proinflammatory mediators lead to NP and allodynia:
Antagonists of TLR4 (stopping cytokine production) reverses NP
Blocking glia activation a target for therapy? Fluorocitrate, minicyclin, propentofylline
IL 1 beta and TNF α antagonists (Embrel®)?
![Page 29: Ansiktssmerter](https://reader035.vdocuments.mx/reader035/viewer/2022062514/55842a21d8b42a86478b4edd/html5/thumbnails/29.jpg)
29 Marchand F et al Nature 2005
![Page 30: Ansiktssmerter](https://reader035.vdocuments.mx/reader035/viewer/2022062514/55842a21d8b42a86478b4edd/html5/thumbnails/30.jpg)
30
Opioids activate glia cells
TLR (toll like receptors) recognise opioids and release neuroexitatory pro-inflammatory cytokines This counteracts opioid analgesia
Prevention of glial cell activation: enhances opioid analgesia prevents opioid tolerance, depencence, withdrawal and
respiratory depression!
Therapeutic target? TLR antagonists (LPS- R/S; naloxone)?
![Page 31: Ansiktssmerter](https://reader035.vdocuments.mx/reader035/viewer/2022062514/55842a21d8b42a86478b4edd/html5/thumbnails/31.jpg)
31 Marchand F et al Nature 2005
LPS
Naloxone
![Page 32: Ansiktssmerter](https://reader035.vdocuments.mx/reader035/viewer/2022062514/55842a21d8b42a86478b4edd/html5/thumbnails/32.jpg)
32
Glia activation - neurodestructive or neuroprotective?
![Page 33: Ansiktssmerter](https://reader035.vdocuments.mx/reader035/viewer/2022062514/55842a21d8b42a86478b4edd/html5/thumbnails/33.jpg)
33
Glia cell activation – neuroprotective?
Remove cell debris which prevents proinflammatory activation
Provide antiinflammatory cytokines IL2, IL4, and IL 10
Is blocking glial activation beneficial?
A neuroprotective activation the new target?
Cannabinoids (CB2) receptors on glial cells Intrathecal administration IL-4 and IL 10 suppresses chronic pain
![Page 34: Ansiktssmerter](https://reader035.vdocuments.mx/reader035/viewer/2022062514/55842a21d8b42a86478b4edd/html5/thumbnails/34.jpg)
34
Gene implantation – the future treatment?
Implantation of ”cytokine” genes may provide prolonged production
Genes enter the cell by endocytosis of a viral vector
Milligan 2009
![Page 35: Ansiktssmerter](https://reader035.vdocuments.mx/reader035/viewer/2022062514/55842a21d8b42a86478b4edd/html5/thumbnails/35.jpg)
35
At the time being
Keep the surgerions away!
Cognitive interventions
Symptomatic treatment?