Pain Flashcards
Contrast the definitions of pain and nociception.
Pain = complex, unpleasant awareness of a sensation modified by experience, expectation, immediate context, and culture
Nociception = non-conscious neural traffic originating with trauma or potential tissue damage
Contrast the definitions of stimulus threshold and tolerance.
Threshold = same in all of us; amplitude of stimulus required to stimulate a response
Tolerance = variable reaction to a painful stimulus; depends on:
- environment
- situation
- psychological/emotional factors
- increases with age
- ongoing pain
- placebo effect
What tracts are responsible for the transmission of pain signals?
ANTEROLATERAL SYSTEM:
DIRECT:
(Lateral) spinothalamic tract = conscious sensation of pain
INDIRECT:
- spinoreticular tract = arousal, wakefulness
- spinomesencephalic tract = activation of desc. inhibition, emotion
- spinotectal tract = reflex eye and upper body and head turning
- spinohypothalamic tract = autonomic and reflex responses
CEREBELLAR TRACTS:
- anterior spinocerebellar
- posterior spinocerebellar
- rostral spinocerebellar
- cuneocerebellar
DORSAL COLUMN (conscious)
- fasciculus gracilis
- fasciculus cuneatus
Contrast the direct and indirect spinothalamic tracts
DIRECT (fast):
- discriminative pain (quality, intensity, location)
- somatotropic organisation
- contralateral
- does not synapse in brainstem
- cortical location is parietal lobe
- also responsible for sensation of temperature and crude touch
- dorsal horn origin: laminae I, IV, V
INDIRECT (slow; 85% of fibres):
- affective aspect of pain (arousal, modification of behaviour, thoughtful/emotional component of pain)
- organisation is not somatotropic
- bilateral
- synapses in brainstem
- subcortical components: hypothalamus (autonomic & reflex responses), limbic structures (emotion, desc. inhibition), autonomic centres, reticular formation (arousal, wakefulness)
- dorsal horn origin in laminae I, IV, V, VII, VIII
Outline the stages of nociception.
- Transduction
- Transmission
- Modulation
- Perception
What is the first stage of nociception?
TRANSDUCTION
Activation of nociceptors by a stimulus (naked nerve endings)
- A-delta fibres activated by mechanical stimulus
- C fibres activated by mechanical, thermal, and chemical stimuli
Lesion causes release of substances which stimulate the nociceptive axon, including: K+, H+, bradykinin, serotonin, prostaglandins,
Nociceptive axon releases substance P which:
- increases local capillary permeability
- stimulates mast cells to release histamine (local oedema, increases sensitivity of axon to pain)
What is the second stage of nociception?
TRANSMISSION
Relay of APs along nociceptive fibres to CNS
A-delta fibres (“ow!”):
- somatic: sharp, stabbing pain (well localised)
- first phase of pain
- lower threshold
- initiates withdrawal reflex
- terminate in laminae I and V
C fibres (“ooh!”):
- visceral: dull, throbbing pain (poorly localised)
- second phase of pain
- higher threshold
- indicates tissue damage occurring
- terminate in laminae I, II (substantia gelatinosa) and V
+ A-beta fibres (light touch) terminate in laminae III, IV, and V
+ spinothalamic tracts originate in laminae I, IV-VII
Nociceptive fibres converge on 2nd order neurones in lamina V
note: substantia gelatinosa = “volume controller”; sets pain threshold by tonic inhibition of laminae I and V (so info cannot leave lamina II)
What is the third stage of nociception?
MODULATION
Inherent modulatory system via inhibition in spinal cord
Central or peripheral
Gate control theory of modulation = rubbing area activates A-beta fibres —> inhibits synapse —> gate closed) e.g. massage, acupuncture, transcutaneous electrical nerve stimulation (TENS)
Central and desc. spinal system = endogenous opioid peptide analgesics (enkephalins, endorphins, dynorphins, endomorphins) and other transmitters (e.g. baclofen - GABA agonist, anti-depressants, anti-convulsants, somatostatin)
What are the endogenous opioid neuropeptides? Which receptors do they each stimulate? What does this cause?
Enkephalins —> delta receptors
Endorphins
Dynorphins —> kappa receptors
Endomorphins —> miu receptors
G-protein coupled receptors inhibit neurotransmitter release by:
- closing voltage-sensitive calcium channels —> inhibits c.AMP formation
- opening potassium channels —> inhibits c.AMP formation
note: descending serotoninergic pathways (regulated by periaqueductal grey matter of midbrain) synapse with substantia gelatinosa to release enkephalins —> closes gate
What is the definition of analgesia?
Inability to perceive pain when tissue damage is occurring
What is the fourth stage of nociception?
PERCEPTION
Interpretation by brain
Thalamocortical projections provide information on location, intensity, and nature of pain
Synapse in primary and association areas and the secondary somatosensory cortex
Emotional response via the limbic system
Stress response via the hypothalamus
What is the pathophysiology of congenital analgia?
Faulty sodium channels or +++endogenous opioid release
e.g. bite off tip of tongue, suspicion of abuse (multiple fractures)
Contrast acute and chronic pain.
ACUTE PAIN:
-
Define hyperalgesia.
Increased pain at normal threshold stimulation (wind-up response)
e.g. touch, temperature
Results from central and peripheral sensitisation
Define allodynia.
Pain from stimuli that are not normally painful OR pain which occurs other than in area stimulated
e.g. patient with osteoarthritis of the knee has pain in thigh (increased size of receptive field)
What is the wind-up response? How does it cause hyperalgesia and allodynia?
Tissue injury and nerve damage cause persistent activation of nociceptive fibres —> excess glutamate release —> excess NMDA receptor activation —> excess 2nd order neurone firing —> hyperexcitable nociceptive neurones
—> hyperalgesia OR allodynia
Describe neuropathic pain.
Burning/electric/tingling/pins and needles/shooting pain
Cannot be explained by a single disease process or specific location of damage e.g. neuropathy, cancer, trigeminal neuralgia
Hyperalgesia and allodynia are almost universal
What is phantom limb sensation and pain? Describe the process by which they occur.
Phantom limb sensation = non-painful sensation in missing limbs
Phantom limb pain = painful sensation in missing limb due to cortical remapping
Changes in physiology of spinal cord (central sensitisation due to wind-up response) increases spinal processing —> changes in functional mapping of brain
e. g. lip sensation encroaches on hand sensation in post-central gyrus —> stroking where they think their hand is will cause sensation in their lips
note: telescoping effect e.g. pain in missing hand, but hand perceived as being attached to their shoulder
Describe the pathophysiology of neuropathic pain.
Peripheral nerve injury sensitisation causes:
- reduced threshold (large afferents sprout from lamina III to laminae I and II —> gain access to spinal regions responsible for high intensity, noxious signals)
- ephapsis (hijacking of adjacent nerve bundles) —> receptive field expansion —> allodynia
- hyperpathia = prolonged post-stimulus sensation
- ectopic excitability = spontaneous activity caused by up-regulation of sodium channels distal to injury (can treat with sodium channel blocker anti-epileptics)
What is complex regional pain syndrome?
a.k.a reflex sympathetic dystrophy
Neurological dysfunction in a limb following trauma, surgery, or disease (diagnosis of exclusion)
More common in women, mean age ~42yrs
Type 1 = no identifiable lesion, occurs after illness
Type 2 = identifiable nerve lesion
Triggers:
- minor trauma
- fracture
- surgery
- stroke
- MI
What are the signs and symptoms of complex regional pain syndrome? How doe they change as the disease progresses?
S&S:
- severe continuous burning pain
- hyperalgesia
- allodynia
- temperature asymmetry
- skin colour changes/asymmetry
- oedema
- changes in sweating/asymmetric sweating
- reduced range of motion
- weakness
- tremor
- dystonia
- trophic changes in hair/nail/skin
Stage 1 = burning/throbbing pain or diffuse aching, sensitivity to touch/cold, localised oedema, vasomotor disturbances (usually normal X-ray; may show patchy demineralisation of involved bones)
Stage 2 (3-6 months) = progression of soft tissue oedema, thickening of skin and articular soft tissues, muscle wasting, development of trophic changes
Stage 3 = limitation of movement, digit contractures, waxy trophic skin changes, brittle ridged nails (X-ray may show marked bone demineralisation)
Outline the effects of opioids.
Analgesia
Resp. depression (opioid receptors in brainstem)
Nausea & vomiting (opioid receptors in brainstem)
Hypotension (opioid receptors in brainstem)
Bradycardia (opioid receptors in brainstem)
Euphoria
Antitussive (suppress coughing)
Constipation
Itching
Tolerance and dependence
Give some examples of adjuvant analgesics which may be used in chronic pain.
Particularly useful for opioid-insensitive pain and neuropathic pain
- NSAIDs
- paracetamol
- capsaicin
- local anaesthetics
- cannabinoids
- ketamine
- tricyclics
- anti-convulsants e.g. gabapentin
Why can a lesion in the posterior part of the thalamus cause pain?
Neurones in this area integrate cutaneous and painful stimuli —> lesion causes painful somatic sensations
note: insensitive to opioids, sensitive to anti-epileptics
Define pain. What are the different types of response to pain?
Unpleasant sensation and emotional experience associated with actual or potential tissue damage
- visceral or somatic
- discriminative and subjective
Autonomic responses:
- raised heart rate
- pupil dilation
- increased resp. rate
Somatic response e.g. withdrawal reflex
Endocrine response e.g. secretion of glucocorticoids/adrenaline
Emotional response
Why do some people initially feel little pain following traumatic injury?
Frontal cortex and somatosensory cortex release opioid neuropeptides —> periaqueductal grey matter of midbrain —–> activates serotonergic and noradrenergic of medulla
- –> enkephalic neurones in dorsal horn
- –> trigeminal nucleus
+ ACTH —> release of endorphins
+ adrenaline —> increased desc. inhibition
