Lecture 33: Pain physiology Flashcards
Define Pain:
Pain is an unpleasant SENSORY and EMOTIONAL experience associated with actual or potential tissue damage, or described in terms of such damage.
What are the four pillars of pain?
Autonomic: HR, BP, RR, Sweating
Motor: Withdrawl, immobil, vocal
Sensory: Where, type etc
Affective: Mood, emotion, Anx, distress
What is the physiological response to pain:
- Inc HR, BP, RR, Blood sugar
- Decrease GI motility, blood flow to viscera, renal, skin
- Nausea, pallor, dilated pupils
What is pain threshold and what is it determined by?
A point at which a stimulus is perceived as pain OR DURATION or INTENSITY of pain that an individual will tolerate before initiation of overt pain response.
- Stress, mood, anxiety, culture, prev exp, activity level, emotion, personality
What can decrease a persons tolerance to pain?
- Repeated exposure
- Fatigue, anger, boredom, apprehension
- Sleep depreivation
What can increase a persons tolerance to pain?
- Alcohol
- Meds, hypnosis
- Warmth, distracting activities
- Strong beliefs or faith
How does age change a person tolerance to pain?
Newborns less sensitive (or cant vocalize)
Children (15-18): Lower than adults
Adults: Pain thresholds tends to increase with age, potentially thanks to neuropathies or thickness of skin
Define analgesia
Absence of pain in response to a stimulus that would
normally be painful
Define anaesthesia
Absence of all sensory modalities
Define hyperalgesia
An increased response to a stimulus that is normally painful
Define allodynia
Pain due to a stimulus that is not normally painful
Define parathesia
An abnormal sensation of burning, numbness, tingling,
itching, prickling -
(usually caused by nerve compression or damage)
Define causalgia
A syndrome of sustained burning pain, and allodynia
after a traumatic nerve lesion.
Define central pain
Pain associated with a lesion of the central nervous system.
What are nocioceptors?
Free nerve endings; Primarily Adelta and C fibers. Respond to mechanical, thermal or chemical stimuli
What are the characteristics of the C fibres?
- Primary afferent fibers
- Small diameter
- Unmyelinated
- Slow conducting (0.5-2ms)
What are the characteristics of A-delta fibers?
- Primary afferent fibres
- Medium diameter
- Myelinated
- Fast conducting (4-30m/s)
What is the pain quality of c fibers?
Diffuse Dull Burning Aching Referred to as 'slow' or second pain
Throbbing, chronic pain
What is the pain quality of A-delta fibers?
Well-localised Sharp Stinging Pricking Referred to as 'fast' or 'first' pain
Quick and intense, beginning of pain
What do c fibers free nerve endings detect?
Mechanical
Thermal
Chemical stimuli.
Polymodal
What do a-delta free nerve endings respond to?
Responds to noxious mechanothermal stimuli over a certain intensity
What are the four processes involved in nocioception?
Transduction
Transmission
Perception (Brain)
Modulation (SC)
Describe transduction:
Noxious stimuli cause cells to release chemicals i.e PG, Bradykinin, Serotonin, Substance P, Histamine -> Activate nocioceptors -> Generation of action potentials
Describe the transmission process:
Nocioceptor excitation is conducted to the sensory cortex via a combination of electric (Action potentials) and chemical (neurotransmitters)
Describe the location of C and Adelta fibre synapses in the dorsal horn… Watch lecture
…
What are the two subdivisions of the spinothalamic tract for pain? and what do they do?
Neo spinothalamic - Lamina 1 -> Post central gyrus (Runs laterally)
Paleospinothalamic - Lamina 2 and 3 -> Reticular formation and limbic system (runs medially) (EMOTION)
Where is pain perceived? and whats the implication of the where?
The reticular system: Autonomic and motor response to pain.
Limbic system: Emotional and behavioural responses
Somatosensory cortex: Perception and interpretation
What are the two ways pain can be modulated?
Dampening
Amplification
What methods dampen/down regulate pain?
- Segmental inhibition
2. Descending inhibitory nerve system
Write some notes on segmental inhibition:
Is based on the premise that a gate, located in the dorsal horn of the spinal cord, modulates the afferent nerve impulses
Implies that a non-painful stimulus can block the transmission of a noxious stimulus
Variables that affect the gate theory of pain down regulation:
- A-delta and c fibers - ‘open the gate’
2. A beta fibers that carry messages of light touch “closes the gate”
What are conditions that open and close the gate?
Open:
Physical: Extent of injury
Emotional: Anxiety, worry, tension
Mental: Focusing on pain, boredom
Close:
Physical: Meds
Emotional: Postive emotions, relaxation
Mental conditions: Intense concentration or distraction, life activities
Describe descending modulatory pain pathways:
Brainstem -> Spinal cord pathways i.e
- Periaqueductal gray area in midbrain by ascending pathways of pain signal, activates neurons that project to locus ceru leus (PONS) and Nucleus Raphe magnus in medulla.
- These have descending neurons that release nor adrenalin and serotonin respectively, that stimulate inhibitory interneurons in the dorsal horn that release enkephalin
Pain amplification is caused by wind-up, what is wind up?
Windup is a term used to describe the process of increased AP output from the dorsal horn cells (second order) in response to SUSTAINED low Hz input from nociceptive afferents via C fibers
i.e sensation of pain is heightened (Hyperalgesia, Allodynia)
What is the mechanism of windup?
Receptors (NMDA, AMPA, NK1) on the DH neurons are stimulated by GLUTAMATE and SUSBTANCE P from the c fibers terminals due to their continuous activation for an extended period of time. This leads to increased Ca influx in the DH neurons.
Consequently, pathophysiological changes take place in the DH neurons LEADING TO LOWERING OF RECEPTORS THRESHOLDS thus becoming MORE RESPONSIVE to all of its inputs. -> Central sensitisation -> hyperalgesia -> Allodynia
What drugs target NMDA and NK1?
NMDA receptor inhibitors ketamine and methadone, KN-1 receptor blocking agents, or calcium channel modulators, prevent windup and may play a central role in managing chronic pain.
What are the types of pain?
- Nocioceptive pain
- Inflammatory pain
- Neuropathic pain
- Referred pain
What is nocioceptive pain?
Due to stimuli from somatic and visceral structures after tissue damage
i.e Chemical, intense heat, mechanical forces
Usually opioid sensitive
What are some algesic substances? and what releases them?
K -> Damaged cells Serotonin -> Platelets Bradykinin -> Plasma Histamine -> Mast cells PGs -> Damaged cells Leukotrienes -> Damaged cells Substance P -> Primary nerve afferents
What causes neuropathic pain? how can it be treated?
Due to damage of neuronal structures
- Usually opioid resistant
- > But sensitive to;
- Membrane stabilizers (gabapentin, carbamzepine)
- Tricyclics (amitriptyline)
- Spinal cord stimulator
What are the types of neuropathic pain?
- Peripheral
- Central
- Complex regional pain syndrome
What are some examples of peripheral neuropathy:
- peripheral (outside CNS)
- Diabetic neuropathy
- Trigeminal neuralgia
- Post herpetic zoster pain
Burning, tingling, shooting, stining, or ‘pins and needles’ sensations
Whats some examples of central neuropathic pain:
- Thalamic pain syndrome (After stroke)
- Damage to spinal cord
What is complex regional pain syndrome?
- AKA Causalgia
Following major injury, pt has severe debilitating pain after recovery.
Signs in affected limb include: Abnormal circulation, temperature, sweating, loss of function, atrophy of muscles, changes in the hair and skin (RELATED TO SNS)
What is the management of neuropathic pain?
Physical therapy
SNS blocks
Medication
The longer it remains untreated, the less chances of reversing the symptoms.
Neuropathic pain frequently coexists with nociceptive pain
What types of inflammation lead to neuropathic pain?
- Non-neurogenic inflammation; Release of inflam substances i.e histamine, PG, Cytokines, Leukotrienes, bradykinin from blood vessels and CT in response to tissue damage.
- Neurogenic inflammation (INCLUDES THE RELEASE OF NEUROPEPTIDES I.E SUBSTANCE P, NORADREALIN) from c fibers terminals.
Both processes lead to lowering the threshold of the receptors leading to hyperalgesia
What is primary vs secondary hyperalgesia?
Secondary is the tissue surrounding the site of damage that becomes inflammed / enhanced sensitisation to pain.
Write some notes on acute pain:
- biologic function
- Acts as a warning system indicating tissue injury
- Recent onset
- Finite duration
- Remits when underlying pathology is resolved
Write some notes on chronic pain:
- No biologic value
- Detrimental effect
- Persists beyond usual course of acute illness or injury
- Chronic pathologic process; can recur at intervals
What is the mechanism of chronic pain?
Neuroplasticity: Changes to the neuronal anatomy and physiology in the dorsal horn
Behavioural and psychological changes
How is pain assessed?
- Verbal scale
- Visual analogue scale
- Numerical
- Wong-baker faces scale
- Objective: McHIll pain questionnaire
Describe the numeric scale of pain:
<4/10 = mild 5-6 = moderate >7/10 = Severe
