Somatosensation Flashcards
Outline pain and the basics of the basic pain pathway
- Pain refers to any unpleasant sensation related to actual or potential tissue damage
- Spinal withdraw mechanisms allow rapid behavioural responses to avoid harm
- It can help us in multiple ways; short pain - withdrawal from source; long pain - promotes resting behaviours; provides social signal
- Mechanical / thermal pain is carried from periphery to CNS by primary sensory neurons whose body are in the DRG (processes called afferents)
- These signals are processed in the dorsal horn to produce responses and signal to the brain
What are the 3 types of primary afferent types and what are their qualities (where do they innovate)
A-beta
- Mechanoreceptors of the skin - touch. Heavily myelinated with fastest conduction speed (35-75m/s)
A-delta
- Pain + temperature, lightly myelinated, medium conduction speed (5-30m/s)
C
- Temperature, pain, itch. Unmyelinated. Slowest (0.5-2m/s)
A-delta and C are peripheral nociceptors that have free nerve endings innervating the epidermal layer of the skin(also innovate bones, organs and blood vessels, but not brain)
A-beta fibres are found deeper in the dermis and are associated with more complex nerve structures
How is pain transduced?
- Polymodal nociceptors with different receptors that trigger different types of pain
- they are polymodal due to the presence of specialised receptors that detect different stimuli
- Heat: TRPV1 (caspsacin) + TRPV2
- Acid: TRPV1, ASIC
- Cold: TRPM8 (menthol) + TRPA1
- Irritants: TRPA1
- There is also evidence that other cell types mediate pain signals - keratinocytes and glial cells
Outline the role of the spinal cord in pain processing and the organisation of the dorsal horn (hint = layers)
- Spinal cord is 30 segments thats split into 4 ares; cervical, thoracic, lumbar and sacral spine
- Sensory input arrives via the dorsal root and leaves via the ventral root.
- The dorsal horn is separated into superficial laminae (layers I + II) and deep laminae (III + IV)
- Nociceptors (high-threshold stimuli); A-delta and C fibres innovate the superficial laminae
- A-beta touch fibres innovate the deeper laminae
- All of these afferents use glutamate as primary neurotransmitter with dorsal horn neurons having AMPA + NMDARs
- IMPORTANTLY: peripheral sensory input can be augmented / inhibited by interneurons OR by descending input from the brain
What type of afferents innovate the deep laminae
Touch (A-beta)
What happens in the ascending pain pathway
- After processing in the dorsal horn, information may be passed to the brain
- Some pain information is passed from the THALAMUS –> SOMATOSENSORY CORTEX
- Some pain processes travel to the PARABRACHIAL AREA —> AMYGDALA (responsible for the emotional feelings of pain)
- Both of these ascending pathways travel via the PERIAQUEDUCTAL GREY in the brainstem and ROSTRAL VENTRAL MEDULLA - both involved in descending pathways that modulate processing in the SC
How was the periaqueductal grey associated with pain
- Stimulation in mice led to analgesia
- Discovered pathway from the PaG to the Raphe nucleus in the medulla
- Involves combinations of 5-HT and opioids
What underlies congenital analgesia?
What is this required to do?
- feeling no pain
- After studying 10yr old street performer in Pakistan, saw a genetic mutation resulting in l.o.f of NaV1.7 channel
- NaV1.7 required to amplify the generator potential to spike threshold in nociceptor terminals in the skin
What is the common feature of the following:
- Painful peripheral neuropathies
- Erythromelalgia
- Channelopathy-associated insensitivity to pain
All effect the NaV1.7 channel
- Enhanced activity
- Enhanced activity
- L.o.F
What is context-induced analgesia and how does it work? (example study)
- Is the feeling of no pain due to extraneous factors such as adrenaline/fight or flight or placebo
- Extreme stress / emotion can affect the periaqueductal grey area in the brain stem, activating the descending pain pathways inducing analgesia
- Double blind placebo trials in patients getting wisdom tooth extraction - 1/3 patients with placebo reported pain relief but when OPIOID antagonist administered, no patients reported pain relief - placebo is mediated by endogenous morphine
What is the role of opioid receptors in the pain pathways
Involved in descending pain pathways to produce analgesic effects
What is the gate theory of pain?
- Is to do with the dorsal horn arrangement of inhibitory interneurons etc and the action of the projection neuron
- Nociceptive fibres (a-delta and C) arrive at the dorsal horn
- C fibre disinhibits the projection neuron to ensure pain signal is transmitted
- A-beta fibres arrive at the dorsal horn at the same time carrying touch information
- It is the function of these A-beta fibres to PROMOTE INHIBITION of these projection neurons by inhibiting them
- Overall effect - pain signal is dampened
E.g., rubbing your knee when you bang it
What is Activity Dependent Slowing
- The phenomenon of the decreased frequency of nociceptive APs from a sustained painful stimulus - an in-built break on pain in our peripheral nerves
- there is a sexual difference in amount of pain-breaking - males have greater pain break than females so greater tolerability to THERMAL pain
- Context: increased number of APs or same number in fort period = more pain
What are some symptoms of chronic pain and how can they occur?
Hyperalgesia - excessive increase of small pain stimulus
Allodynia - when a non-painful stimulus is perceived as painful
Spontaneous pain
Can develop from tissue injury (inflammatory pain, usually adaptive as avoids contact with injured area) and damage to nerves (neuropathic pain, always maladaptive)
What causes inflammatory pain and neuropathic pain
- Damaged tissue causes release of inflammatory mediators such as bradykinins and PGs that can both activate the pain pathway AND modify it
- Direct damage to nervous system can be caused by mechanical trauma, metabolic disease, infection, neurotoxins etc. An e.g. - multiple sclerosis
