Pain and Analgesia Flashcards
(14 cards)
Define pain and explain how it differs from nociception
An unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage
2 components:
- unconscious detection of harmful stimuli using sensory receptors, referred to as nociception
- strong emotional response to pain
Nociception - purely physiological process of detecting noxious stimuli via nociceptors. Unlike pain, nociception does not necessarily involve conscious perception
Describe the structure of the nociceptor and it’s distribution throughout the body
Receptor type associated with pain and it is a simple free nerve ending
Found in skin, muscles, joints, periosteum, and some internal organs
Aδ fibres - myelinated nerve fibres which exhibit rapid conduction velocity
C fibres - unmyelinated nerve fibres exhibiting slow conduction
Explain the difference between fast and slow pain
Fast pain:
- carried by Aδ fibers, thinly myelinated, medium diameter
- sharp, localised pain
- travels quickly to brain via neospinothalamic tract
- felt more superficial
Slow pain:
- carried by C fibres, unmyelinated, small diameter
- dull, aching, poorly localised pain
- travels via the paleospinothalamic tract, reaching deeper brain structures
Identify chemical, mechanical and thermal mediators of pain
Chemicals:
- K+ released from damaged cells activates nociceptors
- histamine and bradykinin, responsible for inflammation changes, are released from mast cells and basophils when IgE coated antigens attach to their surface
- tissue damage stimulates the production of prostaglandins and bradykinin, increasing nociceptors’ sensitivity without activating them
Mechanical:
- strong pressure on nociceptors
- tissue distortion e.g swelling compressing nerves
Thermal:
- Heat (>45°C) – TRPV1 receptor activation
Cold (<5°C) – TRPM8 receptor activation
Describe the pathways nociceptive signals take to reach the appropriate parts of the brain
Peripheral nociceptors detect stimuli - Aδ or C
First order neurones (Aδ or C) carry signals to the spinal cord (dorsal horn), glutamate and Substance P transmit the signal across synapses
Somatosensory cortex on the opposite side of the brain receives these signals
In dorsal horn, first and second order neurones synapse in the substantia gelatinosa
Second-order neurones cross over (decussate) in the spinal cord via the anterior white commissure → ascend via the spinothalamic, spinoreticular or spinomesencephalic tract
The thalamus relays signals to sensory, emotional, and cognitive brain regions
Spinoreticular tract innervates the hypothalamus and limbic system, triggering a fight or flight response
gracile fasciculus carries visceral pain signals
What is the importance of pain ?
Protective function: Alerts body to injury and prevents further damage.
Encourages healing: Reduces movement to allow tissue repair.
Evolutionary survival advantage: Avoidance of harmful stimuli
Congenital Insensitivity to Pain - rare genetic condition resulting from abnormally low expression of nociceptors
Patients often unaware of ischaemic pain, leading to necrosis and bed sores
Describe how the somatosensory cortex, hypothalamus and limbic system contribute to the sensation of pain
Somatosensory cortex:
- processes pain location and intensity
- receives pain signals via the spinothalamic tract from the thalamus
- primary and secondary SCs
Limbic system (amygdala, hippocampus):
- emotional and memory-related aspects of pain
- amygdala links pain to fear and anxiety
- hippocampus associates pain with memories
- anterior cingulate cortex involved in the distress and suffering associated with pain
Hypothalamus:
- body’s autonomic and hormonal responses to pain
- helps regulate stress responses via the hypothalamic-pituitary-adrenal (HPA) axis, leading to the release of cortisol and other stress hormones
- also influences heart rate, blood pressure, and body temperature during painful experiences
Describe the phenomenon of referred pain and explain why it is thought to occur
When pain from a visceral organ is felt in a superficial area of the body
Due to converging afferent pathways in the spinal cord.
Signals from deep structures and superficial areas share the same spinal neurone and synapse in same location → brain misinterprets origin
Pain often felt superficial rather than deep
E.g - heart attack → pain in the left arm, jaw, neck
Explain the difference between acute and chronic pain
Acute:
- short term, resolves with healing
- e.g cuts, burns
- a sudden onset in response to a discrete event
Chronic:
- persists beyond healing
- can be neuropathic (due to nerve damage) or inflammatory
Describe the characteristics of neuropathic pain and it’s underlying causes
Neuropathic pain occurs as a result of a lesion or disease in the peripheral or central nervous systems
associated with :
- allodynia: pain triggered by normally non-painful stimuli
- hyperalgesia: increased sensitivity to painful stimuli
Peripheral sensitization: Increased Na+ channels → spontaneous activity.
Central sensitization (wind-up): Repetitive glutamate release → increased NMDA receptor expression → lower pain threshold.
Phantom limb pain: Central sensitization & cortical remapping.
Identify types of pain which occur during or after exercise and their possible causes
Acute Exercise Pain: Due to lactic acid buildup (H+ accumulation), muscle strain
Delayed Onset Muscle Soreness (DOMS): Micro-tears in muscle fibres, peaks 24-48 hours post-exercise
Chronic Pain Post-Exercise: May indicate nerve compression or joint damage
Describe the analgesic descending pathway
Neuron activation in the hypothalamus initiates the pathway
Signals are relayed to the mesencephalon and upper pons, then to the raphe magnus nucleus (RMN).
From RMN, signals reach inhibitory interneurons (enkephalin neurons) in the dorsal horn of the spinal cord.
Serotonin mediates neurotransmission between these neurons.
Inhibitory interneurones release GABA and enkephalin to prevent further transmission by 2nd order projection neurones.
Active C or Aδ fibres stimulate the DHNs while inhibiting the interneurones.
The release of enkephalin inhibits pain signal transmission by activating µ opioid receptors in C and Aδ fibres and dorsal horn neurones
Enkephalins act presynaptically on C and Aδ fibres by preventing the opening of Ca2+ channels to inhibit neurotransmitter release
Modulates pain at the spinal cord level via endogenous pain inhibition.
Key Structures:
- Periaqueductal gray (PAG) in midbrain → initiates analgesia.
- Rostral ventromedial medulla (RVM) → inhibits pain transmission in the dorsal horn.
- Endorphins and enkephalins: Block pain signals by inhibiting substance P release.
Identify three types of analgesics and explain how they work:
Non-steroidal anti-inflammatory drugs:
- damaged tissue activates phospholipase A2, forming arachidonic acid, which is converted into cyclic endoperoxides, prostaglandins, and thromboxane A2, causing inflammation and vasodilation
- NSAID inhibits COX-1 & COX-2 enzymes → reduces prostaglandin production → decreases inflammation and pain
- e.g ibuprofen
Opioids:
- binds to μ-opioid receptors in the brain and spinal cord
- inhibit pain signals at the spinal cord level and activate the descending pathway without requiring a PVN signal
- e.g morphine, codeine
- very addictive
- side effecrs include respiratory depression, stimulation of the chemoreceptor trigger zone in the medulla results in nausea and vomiting
Local Anaesthetic:
- block pain fibre’s action potential by physically plugging voltage-dependent Na+ channels
- gain access to channels through two pathways
- ionised: at physiological pHs, which directly permeate the channel
- unionised: which indirectly access the channel pore
Analgesic Pathway basic:
Activated in extreme stress (stress analgesia).
Pathway: Hypothalamus (PVN) → Midbrain (PAG) → Pons (RMN) → Dorsal horn inhibitory interneurons.
Mediators: Serotonin (5-HT), GABA, enkephalins (endogenous opioids).
Effects: Blocks neurotransmitter release (presynaptic inhibition) & prevents DHN activation (postsynaptic inhibition).
