L31 & 32 - Pain Control Flashcards
What is pain?
Unpleasant sensory and emotional experience associated with actual or potential tissue damage
Chronic pain is defined as pain lasting for x amount of time
More than 3 months
Broad groups of pain
1) Defined nociceptive basis e.g. chronic arthritis
2) Well-defined neuropathological basis - e.g. postherpetic neuralgia, phantom limb pain
3) Idiopathic - pathogenesis not well accepted e.g. chronic musculoskeletal pain
Nociceptive circuit
1) Noxious stimuli
2) Activation of peripheral termal
3) AP
4) Dorsal horn
5) CNS neurons
6) Brainstem areas, thalamus, cortex -> action
7) Descending modulatory control pathways
List 2 thermal receptors
TRPV1/2
List a few chemical receptors
ASIC, P2X, P2Y, B1, B2 (bradykinin)
Which cortical area is involved in descending modulatory control?
Brainstem
Major inhibitory NT in dorsal horn
Gly, GABA, opioids, NA, 5-HT
T/F - Inhibitory NT only act presynaptically
F - they act pre and post e.g. miu opioid receptors on both
How is presynaptic inhibition mediated?
Inhibition of Ca2+ voltage sensitive channels
e.g. opioid miu receptor, alpha-2 adrenoceptors, cannabanoid CB1 receptor(All are negatively coupled to Ca2+ channels),
How is postsynaptic inhibition mediated?
Enhanced Cl- influx and K+ efflux
What pharmacological treatments (for acute pain) would you give in mild, moderate, severe pain?
Mild - Paracetamol
Moderate - Paracetamol, oral opioid, NSAID
Severe - Same as mod but increased oral opioid dosage with i.v./s.c. opioid or transdermal fentanyl patch
Pharmacological treatment for chronic pain?
Opioid therapy
List two naturally occurring opioids and 2 synthetic
Natural - Morphine, Codeine
Synthetic - Fentanyl, Methadone
Where are miu opioid Gi found?
Brain, spinal cord, peripheral tissues - acting on primary sensory, local-circuit interneurons and descending inhibitory fibres to inhibit central relaying of nociceptive stimuli
In what areas of the brain do opioids induce analgesia in?
Cortex, PAG region, medulla, dorsal horn - enhancing descending inhibition to dorsal horn
Morphine actions and side effects? How about its actions in the periphery?
Actions:
Euphoria, Analgesia, Sedative, respiratory depression (due to decreased sensitivity of medullary resp centre to CO2)
SE:
Nausea, miosis, antitussive
Periphery:
GIT (constipation) due to miu receptors on myenteric neurons decreasing ACh release, decreased motility, urinary retention, CV decreases sympathetic tone due to orthostatic hypotension and bradycardia, Histamine from mast cells = vasodilation, bronchoconstriction, itching
What does morphine tolerance affect and doesn’t affect (in terms of its actions and side effects)?
Affects euphoria, analgesia, sedative, resp dep, nausea
NOT constipation, miosis
Nalaxone - what is it? Treats? metabolism?
Opioid Antag that has affinity for ALL opioid R
Treats overdose and induces withdrawal
Metabolised rapidly with half life of 1 hour so given i.v
For chronic pain, opioid therapy only works in _ of patients and decreases pain by up to __
1/3, 50%
Does neuropathic pain have poor or good response to opioids?
Poor
Mechanisms of neuropathic pain
- Inflammatory cytokines from macrophages and schwann cells and loss of support from neurotrophic factors
- Nav1.3 channels (not normally detectable) are up-regulated - more AP = more cytokines
What happens during withdrawal of peripheral trophic support?
C-fibres lost and Abeta-fibres invade space normally occupied by C-fibre terminals - this results in responding to non-noxious stimuli (A-beta fibres) as noxious (C-fibres)
Excitotoxic loss of inhibitory neurons in dorsal horn -> loss of inhibition -> heightened pain sensitivity
Subunits of Voltage-gated Ca2+ channel pore
4 subunits
alpha 1 = 4 homologous domains, with 6 TM segments = the pore forming subunit
alpha 2 delta = ANCILLARY subunit - extracellular modulator function
