What is pain?
An unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage
What is the difference between nociception and pain?
Nociception is a sensory process
Pain is a higher order process that requires higher order processing
Describe the process of nociception?
1. Transduction: nociceptors detect physical force on tissues
2. Transmission: peripheral and central, in lateral spinothalamic tract
3. Perception: sesnory and emotional, cortical input
4. Modulation: can interfere with transmission of information or act at a higher level
What are the two classes of adaptive/protective pain?
What are the two classes of maladaptive/pathological pain?
Functional pain syndromes
Briefly describe the broad pathway for nociceptive pain?
Noxious stimulus (temperature, force, chemical) > nociceptor sensory neuron > spinal cord > response (withdrawal reflex) > pain (adaptive, high-threshold)
Describe the somatosensory neurons involved in nociception?
Unmyelinated C-fibres: thin, slow transmission, enter at most supericial layers of dorsal horn
Myelinated Ad fibres: thin, fast transmission, enter at superficial and deeper layers of dorsal horn
Why are two different fibre tyes involved in nociception?
Ad fibres are rapid, and give info about sharp pain
C fibres are slower, and give info about slow, burning pain
First and second pain
How do second order neurons project to the brain in the nociceptive pathway?
Why do spinal nociceptive reflexes not result in pain?
Nociceptive fibres only make connections in the spinal cord
They connect to motor neurons to cause muscle contractions
Brain not involved > no pain
Describe the relationship between pain, time and stimulus intensity for nociceptive pain?
What is required for the perception of pain?
Sensory info must be decoded in the cortex
Briefly describe the broad pathway of inflammatory pain?
Peripheral inflammation > inflammaory cells and tissue damage stimulate nerve endings > spinal cord > spontaneous pain, pain hypersensitivity > adaptive, low-threshold pain
What is the stimulus for inflammatory pain?
Inflamed or damaged tissues release nociceptor sensitisers
Which types of receptors are involved in nociceptor transduction?
What is sensitisation?
Two types: peripheral and central
Peripheral sensitisation involves acting on nerve endings to make them more sensitive to stimuli
Central sensitisation involves acting on on the central pain system to make it more sensitive
What are the outcomes of central and peripheral sensitisation?
Peripheral sensitisation: from innocuous stimulus > primary allodynia; from noxious stimulus > primary hyperalgesia
Central sensitisation: from innocuous stimulus > secondary allodynia; from noxious stimulus > secondary hyperalgesia
What are hyperalgesia and allodynia?
Hyperalgesia: an increased response to a normal stimulus
Allodynia: a painful response to a normally innocuous stimulus
What is secondary hyperalgesia?
Following central sensitisation in the spinal cord, the hyperalgesia may spread to areas which are not physically damaged
Describe the relationship between pain, time and stimulus intensity for inflammatory pain?
Which class of pain are peripheral and central sensitisation associated with?
Describe the broad pathways of neuropathic and dysfunctional pain?
Neuropathic pain: neural lesion > spontaneous pain and hypersensitivity > maladaptive, low-threshold pain, disease state
Dysfunctional pain: no neural lesion > spontaneous pain and hypersensitivity > maladaptive, low threshold pain, disease state
Describe how/why peripheral neuropathic pain occurs?
Damage to sensory nerves > changes in terminal fields > start to generate pain signals without sensory stimulation
Can happen anywhere in pathway
Describe the relationship between pain, time and stimulus intensity for neuropathic pain?
Using fMRI imaging, which parts of the brain appear to be activated when someone is in pain?
Sensorimotor part of cortex
Info coming up through spinal cord separates in thalamus and splits into these two areas
Give examples of the major classes of centrally acting analgesic drugs?
How do analgesic drugs work?
Some interfere with transmission of sensory information from sensory neurons to projection neurons, therefore blocking pain related information transmission
Some activate the PAG pathway, which relays through the medulla then projects to the dorsal horn
Describe endogenous pain modulation?
System is bimodal - can facilitate pain as well as inhibit pain
Describe the relationship between anxiety/fear and apin?
Anxiety and fear can induce hypoalgesia
Endogenous inhibition of pain sensitivity
Describe the top-down psychological modulation of pain?
Cortical areas (anterior cingulate, PFC and insula) can alter pain sensitivity
Describe the effects of placebo and nocebo on pain?
Substituting a placebo for an active treatment alters pain matrix activity in neuroimaging and produces genuine analgesia via endogenous pain modulation (reduced or prevented by opioid antagonists)
Expectations of pain produce activity changes, but these correlate with nocebo hyperalgesia