Pain and general drugs Flashcards
Difference between nociception and pain
NOCICEPTION = the neural processing of pain without the emotional effects/stimulus
PAIN= An unpleasant sensory and emotional experience resulting from potential or actual tissue damage
Define convergence
A single sensory neurone within CNS can reveive inputs from many peripheral receptors
Transduction mechanism in pain
- Deformation of membrane
- K+ and na+ channels open
- Receptor potential
- Ap propogated to CNS
Stronger stimulus; stronger receptor potetntial; greater number and frequency of APS
C fibre characteristics
- unmyelinated fibres
- slow conduction velocity
- terminate in superficial lamina I-II of dorsal horn
- Responses sensitive to glutamate receptor
Allodynia
Non-painful stimulus perceived as painful
Hyperalgesia
Painful stimuli becomes more painful
Which part of thalamus is pain relayed to
Ventral posterior nucleul
Through which structures does the inhibitory pathway for pain run
PAG
NRM
SPinal cord
Substance that blocks effect of morphine
Naloxene
Normal neuronal transmission
- AP causes voltage gates ca2+ channels to open which bind to vesicles containing NT
- Vesicles migrate and fuse with membrane, releasing NT
- If enough NT binds post-synaptically and exceeds threshold; AP
Neuronal transmission inhibition by opioid
- Activated Gi; decreases cAMP via decreased AC; alters protein kinases, influences excitability
-
Opening/closing of ion channels
- Closure of Ca channel: no Ca can enter, vesicles cant release NT
- Increase K+ efflux: Lowers membrane potential; hyperpolarisation i.e. less excitable
Post-synaptic K channels can also be affected in same manner
Effect of sustained morphine exposure
Tolerance
Uncoupling of G-protein; lowered effect
Dependence
Importance of m-opioid receptor location within spinal cord
STT mainly synapses with C fibres in superifical lamina of dorsal horn, whilst AB fibres synapse more deeply. Since the opioid receptors also are superficially placed tactile pathways arent affected too much
How do opioids effect descending inhibitory control of pain
Receptors also at PAG and NRM
limitation of opioid treatment in neuropathic pain
In neuropathic pain both A/C fibres are involved. C drives hyperalgesia. A fibres produce pain state known as allodynia; pain from stimulus not normally painful
- Hard to treat with analgesics due to lack of opioid receptors on A-fibres, only treats hyperalgesia
- Can use Pregab
Characteristics of Dia-morphine
Higher lipophilicity - rapid brain penetration
Broken down to morphine in CNS
More potent and addicitve than morphine
COX 1 vs COX 2
COX1
- Constitutive enzyme; always expressed in most tissues and platelets
- Involved in normal homeostasis
- Generally wan’t to keep unaltered in treatment
COX2
- Induced in activated inflammatory cells following tissue damage
- Enzyme responsible for production prostaglandins from arachadonic acid
Which cells release PGD2
Normally mast cells
In chronic inflammation also monocytes and macrophages can release PG2/TXA2
PGE2, PGI2 and PGD2 effect on inflammation
Powerful vasodilators. Increased blood flow to site of inflammation and increased leakiness of vessels. Synergise with histamines to cause itch and bradykinin to cause pain
Effect of Bradykinin in inflammation
- Synthesised de novo during damage
- Activated nociceptiors by B1 and B2 G-protein coupled receptors
- Increases PG production, reinforces PG response
- PG enhance nociceptors response to BK, vicious circle
Define antipyretic
Reduces fever
Body temp regulated by hypothalamus. NSAIDs reset the thermostat by blocking effect of PGs on hypothalamus
Aspirin mode of action
Irreversible inhibition of COX1 and 2
Anasthesia is an insensitivity to pain following suppression of:
- Afferent sensory reflex - Local/regional anesthesia
- Central neural processing - general anesthesia
Local anaesthetic - mode of action
- Block na+ channels; AP not going to brain about pain
- Administered as a weak base or uncharged/lipid soluble molecule for cell entry
- Often given with vasoconstrictor e.g. adrenaline to enhance the duration of drug by causing partial ischaemia to area
