Ansiktssmerter

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Gunnvald Kvarsteingunnvald.kvarstein@rikshospitalet.no

Orofacial pain - a neuropathic pain syndrome?

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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

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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

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Dental pain

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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.

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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

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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

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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

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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

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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

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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.

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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

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Thermo test

Heat pain tolerance Heat pain

Neutral

Cold

Cold pain

Heat

Patients respond to standardized thermal stimuli

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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.

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Phenotypic mapping:

Standardised QST protocol to determine the mechanisms and design a mechanism-based treatment

German Research Network on Neuropathic Pain, Baron R 2006

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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

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Neuropathic pain based on

complex mechanisms!

Central and peripheral mechanisms

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Animal pain research- nerve injury models provide new

insight to the mechanisms

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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

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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?

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Ion channels and receptors are translocated to intact neurons Na channels TRPV1 (vanilloid) adrenoceptors

Baron R 2006

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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

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Evidence for activated glia

cells

Astrocytes in spinal cord activated after sciatic nerve damage

Garrison et al 1991

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A close interplay

Glutamate

27 Marchand F et al Nature 2005

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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®)?

29 Marchand F et al Nature 2005

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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)?

31 Marchand F et al Nature 2005

LPS

Naloxone

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Glia activation - neurodestructive or neuroprotective?

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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

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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

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At the time being

Keep the surgerions away!

Cognitive interventions

Symptomatic treatment?