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Microsoft PowerPoint - PAIN intro

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					     NEUROBIOLOGY OF
                                                                      The Dimensions of Pain
          PAIN
                                                                 • Sensory Dimensions
            “An unpleasant sensory or                                 -quality and location
           emotional experience that is                          • Primary Affective Dimension
        associated with actual or potential                           -unpleasantness, distress, fear
             tissue damaging stimuli”
                              stimuli                            • Secondary Affective Dimension
                                                                      -anxiety and depression




 AMYG                         PAG
                                                     SI
                 PBN                                                  Good Pain
  VMH                                       Pain
                   L              N
                   C
                                  R
                                  M
                                          location
                                               VPL    VPM
      Pain
                                                     PO
      affect
                       I      I

                                        Pain
Noxious                SPB
stimulus                              modulation
                             STT
(Aδ/C)                       SRT




      Nociceptive (“good”) pain                                      Evolution of pain theories
 •Requires a noxious stimuli.                                   Hard wired
                                                              Nervous System
 •Protective function (preserves tissue integrity).




                                                      brief
                                                               Accounts for
                                                              “good” but not
 Acute (brief)               CNS                     Pain       “bad” pain
   injury




                                                                                                        1
                                                    Neuropathic pain
                         Bad pain       Pain due to dysfunction or damage to peripheral nerves
                                        Pain persists in the absence of the initial injury




                                                                 +
                                                                                  ABNORMAL




                                        PNS or CNS            CNS                   Pain
                                          damage




                                            Abnormal Sensory Processing

                                         Innocuous
                                           Stimuli
        DCN                       NTS
                                            (Aβ)                              Pain:
                                                                             allodynia
              Cord
                                          Noxious                           hyperalgesia

                                          Stimuli
                                          (C/Aδ)




              Definitions
• Hyperalgesia: increased pain in
 response to a painful stimulus

• Allodynia: pain in response to an
 innocuous stimulus

• Spontaneous pain: pain in the
 absence of a stimulus




                                                                                                 2
     Classification of neuropathic                                            “Bad” pain
                  pain                                     •Mechanical trauma        Neuropathy, avulsion
                                                           •Compression       Disk herniation, carpal tunnel
                        • Type
                                                           •Inflammation                           RA, OA
                       • Location                          •Infections               Herpes zoster, syphilis,
                                                                                                                  AIDS
                                                           •Neurotoxicity                                     Cisplatin
            • Presumed mechanism                           •Disease                                            Cancer
                                                           •Ischaemia                            Thalamic syndrome
         • Pharmacological response                        •Metabolic                                         Diabetes
                                                           •Immune system                                    MS, AIDS
                                                           •Autonomic system                                    CRPS




 Classification of neuropathic pain                           Mechanism based classification
               by site                                       Acute pain:
                                                                   pain                          Nociceptor specialisation

                                                            Tissue injury pain:
                                                                          pain                    Peripheral sensitisation
Peripheral             Spinal               Brain                                                      Silent nociceptors
                                                                                                    Phenotypic switching
Neuropathy             Multiple sclerosis   Stroke                                                    Hyper-innervation
Amputation             spinal cord injury   MS                           Central sensitisation, summation, amplification
Nerve injury           Spinal stroke        Neoplasm
Plexopathy             Syringomyelia        Parkinson’s?   Nervous system injury pain:
                                                                                 pain                 Spontaneous activity
Radiculopathy          Neoplasms            Epilepsy?                                             at site of injury, or soma
Avulsion               Arachnoiditis                                                                 Phenotypic switching
Trigeminal Neuralgia                                                                                         Disinhibition
Neoplasm                                                                                              DHN deafferentation
Herpes Zoster                                                                                          Central sensitization
                                                                                                Structural rearrangement




                                                                 PERIPHERAL SENSITIZATION
     Pharmacological classification                        Tissue     Inflammation  Sympathetic
                                                           damage                     terminals
                                                                                Sensitising ‘soup’
                                                            H+      K+      5-HT         Neuropeptides
                                                            Bradykinin      Noradrenaline     Prostaglandins
                                                            Purines    Cytokines (IL1, IL6)         Histamine
                                                            NGF        COX2
                                                                                         High Threshold Nociceptor

                                                           Transduction sensitivity
                                                                                        Low Threshold “Nociceptor”




                                                                                                                               3
     CENTRAL SENSITISATION                                Peripheral      vs                Central
                                                                    Sensitisation
                            Nociceptor input
                                                      • ↓ threshold for           • ↑ responsiveness of
                                                        activation in               DHNs in CNS
                         Activity dependent             nociceptor                • Triggered by nociceptors
                       increase in excitability
                                                      • ↑ response to stimulus      and outlasts stimulus
                              of DHNs                   due to sensitizing soup   • Is responsible for 2o
 Low threshold                                          in periphery.               hyperalgesia
 mechanoreceptor               Modified               • Innocuous stimuli         • Input from Aβ fibres
 (Aβ) input                  responsiveness             cause pain by               produces pain by
                                                        activation of               changes in sensory
                                                        sensitised Aδ/C fibres      processing in the spinal
                               PAIN                                                 cord
                              (allodynia)




Biological importance of central sensitisation
                                                                       Acute pain
                                                                                    • Activated areas:
                                                                                    • Hypothalamus &
                                                                                      PAG (Brain defence
                                                                                      mechanisms)
                                                               FMRI/ PET SCANS
                                                                                    • SI & MI
                                                                                      (localisation)
                                                                                    • PFC - behavioural
                                                                                      response to pain




                                                    Pain as a biological               “to find optimal pulse
                                                                                    parameters to evoke peak
   Chronic pain: mononeuropathy                          weapon!                   nociceptor activation” i.e.
 • Limbic system                                                                   cause the maximum pain
                                                                                                     possible
   – Insula (integrative)
   – ACC (emotive)

 • PFC - behavioural
   response to pain

 • Thalamus
                                                  New
                                                  Scientist 03/05




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