Pain Flashcards
define pain
“An unpleasant sensory and emotional experience, associated with actual tissue damage or described in terms of such damage”
name the 3 forms of pain
(i) Nociceptive (acute) pain (e.g. pin prick, visceral distension)
(ii) Inflammatory (prolonged) pain (e.g. sunburn, inflamed wound)
(iii) Pathological pain
nociceptive pain begins with the activation of ………
nociceptors
-> specific peripheral primary sensory afferent neurons normally activated preferentially by intense stimuli
name 3 types of intense stimuli?
thermal, mechanical, chemical
what are the cell bodies associated with nociceptive pain pathway?
- dorsal root ganglia
- trigeminal ganglia
what are nociceptors?
they are primary afferent neurons innervating peripheral tissues—activated only by mechanical, thermal, or chemical stimuli that are noxious. Comprise Aδ- and C-fibres. Transduction begins in free nerve endings—mediated by numerous receptors and channels.
they are first order neurons that relay information to second order neurons in CNS by chemical synaptic transmission
nociceptive pain is ….. and ……
nociceptive pain is adaptive and is high threshold
- i.e. serves as an early warning system to minimise contact with damaging stimuli (noxious events) and provoked only by intense stimuli that activate nociceptors
inflammatory pain is ……. and ……..
- inflammatory pain is adaptive and protective
-> produces pain hypersensitivity
activates immune system in response to injury, or infection
assists in healing of a damaged body part
define allodynia
pain in response to a nonnocipetive stimulus e.g. cold temperature or light stroke
Nociceptive pain diagram
Inflammatory pain diagram
Pathological pain diagram
what is the condition congenital insensitivity to pain? (CIP)
results due to loss of function mutations (missense, or in frame, deletions) in the gene SCN9A that encodes a particular voltage-activated Na+ channel (Nav1.7) that is highly expressed in nociceptive neurons
can result in:
- lip and tongue injury
- bruises and cuts
- multiple scars
- bone fractures
- joint deformity
- premature mortality
what do meissner corpuscles respond to?
touch
what do pacinian corpuscles respond to?
pressure
what do ruffini endings respond to?
pressure
what do the terminals of nociceptor neurons transduce a stimulus into?
electrical activity
-> stimulus (mechanical, thermal or chemical) opens cation-selective ion channels in nerve terminal to elicit a depolarising receptor potential
what do low threshold units do?
respond to low intensity (non-damaging and non-painful)
-> LTM (low threshold mechanoreceptors): mediate touch, vibration and pressure
what do high threshold unit do?
- nociceptors: respond to high (noxious, potentially damaging) but not normally low intensity stimuli
-> HTM’s also called mechanical nociceptors respond to high intensity mechanical stimuli
what are thermal nociceptors?
- respond to extreme degrees of head >45 degrees or cold <10-15 degrees
what are chemical nociceptors?
respond to substances in tissue (as found in inflammation) e.g. prostaglandins, bradykinin, serotonin, histamine, K+, H+ and ATP and many others.
what are polymodal nociceptors?
respond to at least 2 of the above
what are the 4 of the axons of the primary sensory afferents from skin
- Aα
- Aβ
- Aδ
- C
what sensory receptor is Aα?
propioceptors of skeletl muscle
- thick myelination
what sensory receptor is Aβ?
mechanoreceptors of skin
what sensory receptor is Aδ?
pain, temperature
- thinly myelinated, responds to fast pain (stabbing)
what sensory receptor is C?
temperature, pain and itch (all noxious stimuli therefore are polymodal)
- unmyelinated, responds to slow pain (burning, throbbing)
what is the bodys natural response after tissue damage?
- peripheral sensitisation
-> mediated by nociceptors at site of innjury/tissue inflammation
-> causes hyperalgesia and allodynia
what tracts are involved in the nociceptive pathway?
- spinothalamic and spinoreticulothalamic tracts
describe nociceptive pathway?
- noxious stimuli stimulates a free nerve ending (either Aδ or C-polymodal)
- first order neurone relays information to DRG or trigeminal ganglion and synapses at dorsal horn of spinal cord
- second order neuron then relays this info to the brain
(in anterolateral system e.g. STT, SR, SM tracts) info travels to thalamus (VP nucleus) and third order neurone passes information to somatosensory cortex (S1)
what is STT tract involved in in pain?
Acts as a ‘warning system’ by signalling the exact location and severity of the injury and the duration of pain. Also analyses the features of the pain – is it burning, sharp, pricking, aching?
- projection neurones originating from lamina 1 (fast fibre Aδ pain) and terminates in post nucleus of thalamus
- signals from thalamus are relayed to somatosensory cortex by thalamocortical neurons
what is the spinoreticular tract involved in in pain?
Registers the emotional/motivational component of pain, its inherent unpleasantness.
- largely transmits slow C fibre pain (poorly localised)
- signals to intralaminar nuclei of thalamus indirectly to brainstem (reticular formation) via reticulothalamic tracts
- ends up in limbic area of forebrain (cingulate and insular cortices)
what is the spinomesenchepalic tract involved in in pain?
This pathway is therefore involved in the modulation of pain, and the emotional component of pain.
- also involved in control and inhibition of pain!!!
- afferents of this tract terminate in periaqueductal grey matter (PAG), and misbrain raphe nuclei.
- both of which give rise to descending fibres that modulate nociceptive transmission
- therefore when PAG is stimulated can activate a natural pain suppression system which involves the release of endogenous opiods
name 3 analgesics in order of weakest to strongest in terms of clinical efficacy
- NSAID (aspirin, diclofenac, ibroprofen)
- Weak opioid (codeine, tramadol)
- Strong opioid (morphine, heroin, fentanyl)
-> combinations of 1+2 or 1+3 are used in mod/severe pain
what is an opiod?
- any agent (inc endogenous peptides,(endorphins/enkephalins) that act upon opioid receptors
what is an opiate?
- substance extracted from opium
how do NSAIDs act?
act to reduce nociceptor sensitization
- inhibit synthesis and accumulation of prostaglandins by COX enzymes (COX-1 and COX-2)
what is the descending supraspinal projections?
- pathway beginning at PAG (gray matter in midbrain) which relays inomayion to RVM. then travel down spinal cord and activate endogenous opiate system to suppress pain
how do opioids work?
- bind to opioid receptors (usually μ-receptors (G protein-coupled receptor)).
- ## small proteins/peptides named enkephalins are the endogenous agonists of opioid receptors.
cellularly how do opioiods work?
- inhibit opening of voltage-activated Ca2+ channels (suppressing presynaptic excitatory NT release)
- opening of K+ channels (suppresses post-synaptic excitation of projection neurones)
where is PAG found?
in the midbrain surrounding the cerebral aqueduct
what else does the PAG do?
- regulates HR and BP
- autonomic processes (bladder control and contraction)
- fearful and defensive reactions
- production of vocalizations
best known for its role in analgesia
