San Francisco Chronicle, June PDF Free Download

PAIN

San Francisco Chronicle, June 2001

CONGENITAL INSENSITIVITY TO PAIN

PAIN IS A SUBJECTIVE EXPERIENCE: It is not a stimulus MAJOR FEATURES OF THE PAIN EXPERIENCE: Sensory discriminative Affective (emotional) Cognitive MEASUREMENT OF PAIN: A BIG PROBLEM

Worst pain ever Visual Analogue Scale (VAS) No pain

O U C H E R S C A L E

DESCARTES

Dorsal columnmedial lemniscal Spinothalamic/ Spinoreticular tract

DESCARTES

ANTEROLATERAL CORDOTOMY (SPINOTHALAMIC TRACTOTOMY)

NEUROSURGICAL PROCEDURES THAT HAVE BEEN USED TO TREAT PAIN

NOCICEPTIVE (TISSUE INJURY) PAIN: (Associated with inflammation) Aches and sprains Back pain Arthritis Temporomandibular joint pain (TMD) Cancer Headache (migraine) Allodynia and hyperalgesia

Nociceptive Pain: Tissue Injury/Inflammation

NEUROPATHIC (NERVE INJURY) PAIN: Reflex sympathetic dystrophy (RSD); causalgia Trigeminal Neuralgia Post-herpetic neuralgia Anesthesia Dolorosa Phantom Limb Pain Cancer

Neuropathic Pain: Nerve Injury (RSD)

Neuropathic Pain: Post-Herpetic Neuralgia

Dorsal columnmedial lemniscal Spinothalamic/ Spinoreticular tract ----IS NOT A PAIN TRACT

So where does specificity break down?

Peripheral nerves contain small and large diameter primary afferent fibers

Myelinated A delta and unmyelinated C fibers only respond to noxious stimulation

But in the setting of tissue injury the small diameter fibers respond to innocuous stimulation: NON-PAINFUL STIMULI NOW HURT!

Tissue Injury Arachidonic acid Cyclooxygenase Prostaglandins C FIBER THRESHOLD LOWERED ALLODYNIA PERIPHERAL SENSITIZATION

NSAIDS Aspirin Ibuprofen Naprosyn (Alleve) Cox-2 inhibitors

Large myelinated afferents (A ) do not respond to noxious stimulation

But activity of large diameter fibers can reduce the pain that results from activity in small diameter primary afferent fibers. SHAKE YOUR HAND; IT HURTS LESS!

Organization of the Dorsal Horn Laminar organization

Organization of the Dorsal Horn Somatic-visceral convergence: Referred Pain

REFERRED PAIN

Organization of the Dorsal Horn CENTRAL SENSITIZATION

Central sensitization: Tissue Damage Nerve Injury

Central sensitization:

CENTRAL SENSITIZATION Pain responsive neurons can now be activated by non-noxious stimuli (allodynia) Receptive field size of dorsal horn neuron increases Spontaneous activity increases

Mechanisms of Central Sensitization Presynaptic: Increased transmitter release C-fiber input Prostaglandin (EP receptor) NMDA AMPA Postsynaptic: increased response to transmitter strengthening of synaptic efficacy Mg ++ ALTERATION IN SECOND MESSENGERS PHOSPHORYLATION OF RECEPTORS AND ION CHANNELS WDR cell INCREASED EXCITABILITY AND SYNAPTIC EFFICACY

And still more contributors to central sensitization

Mechanisms of Central Sensitization: Descending influences Facilitation Inhibition (SNRI) 5-HT and NE Glutamate GABA (Anticonvuslants) Glycine

And neurons are no longer the only target: The contribution of glia

Microglia Quiescent glia Ipsi Contra Nerve injury Activated glia

Organization of the Dorsal Horn Ascending pathways

Dorsal columnmedial lemniscal Spinothalamic/ Spinoreticular tract

Dimensions of Pain Perception Sensory-Discriminative Stimulus features: Location, Modality, Intensity Affective-Motivational How unpleasant or upsetting is the pain? What will I do about the pain?

Dorsal columnmedial lemniscal Spinothalamic/ Spinoreticular tract

Nociceptive neurons in lateral, medial and posterior thalamus

Somatosensory cortex

Pain activates sensory cortex S1 S2

Somatosensory cortex Anterior cingulate cortex Insular cortex

Pain activates limbic cortex ACC IC

Pain affect without pain sensation in patient with postcentral lesion (Ploner et al. 1999)

But exactly where and to what extent? It depends.

It depends on. what part of the body was stimulated.

Esophageal distension vs noxious thermal heat Insular Cortex QuickTime and a TIFF (Uncompressed) decompressor are needed to see t his picture. Motor Cortex Anterior Cingulate Cortex Strigo, I. A. Bushnell, M. C. Alert

It depends on. who was stimulated.

QuickTime and a TIFF (Uncompress ed) decompressor are needed to see this picture. Male Female From Casey et al

It depends on. how much attention is paid to the stimulus.

Pain evokes more brain activity when attending to pain Attention to pain Attention to tones Bushnell et al. 1999

It depends on. how much pain you expect to experience.

Expectancy can alter pain Pain Warm Warm (expect pain) (expect pain) (expect warm) Sawamoto et al. 2000

PAIN CONTROL

PAIN CONTROL PROCEDURES Aspirin and other NSAIDS (ibuprofen; COX-2 inhibitors) Transcutaneous electrical nerve stimulation (TENS) Deep brain stimulation (DBS) Morphine and other opioids Placebo Acupuncture Stress/other psychological mechanisms Hypnosis

PAIN CONTROL PROCEDURES Aspirin and other NSAIDS (ibuprofen) Transcutaneous electrical nerve stimulation (TENS) Deep brain stimulation (DBS) Morphine and other opioids Placebo Acupuncture Stress/other psychological mechanisms Hypnosis

DEEP BRAIN STIMULATION

DEEP BRAIN STIMULATION MODULATION NALOXONE OPIATES + - Dorsal Periaqueductal Gray Nucleus Raphe Magnus horn

ENDORPHINS Enkephalin Dynorphin Endorphin Opioid Receptors NALOXONE

PAG stimulation evokes the MODULATION release of endorphins to initiate descending inhibition and pain OPIATES control NALOXONE is the key to this interpretation. DEEP BRAIN STIMULATION Periaqueductal Gray (PAG) Nucleus Raphe Magnus (NRM) Dorsal horn

ENDORPHINS Enkephalin Dynorphin Endorphin Endogenous Opioid Receptors Exogenous Morphine and other opiates

OPIATE ANALGESIA MODULATION OPIATES SYSTEMIC MORPHINE Periaqueductal Gray Nucleus Raphe Magnus Dorsal horn

SIDE EFFECTS MODULATION OPIATES SYSTEMIC MORPHINE OPIATE ANALGESIA Periaqueductal Gray Nucleus Raphe Magnus Dorsal horn GUT (CONSTIPATION)

OPIATE ANALGESIA MODULATION OPIATES EPIDURAL MORPHINE Periaqueductal Gray Nucleus Raphe Magnus Dorsal horn

MORPHINE

S1 Rainville et al 1997 Before Hypnosis ACC Rainville et al High Unpleasantness

S1 ACC Under Hypnosis Rainville et al HIGH Unpleasantness LOW