pain pharmacology Flashcards
what is somatic pain
cutaneous, musculoskeletal tissue or peritoneal membranes
what is visceral pain
thoracic or abdominal organs
what is neuropathic pain
from a injury to the peripheral or central nervous system
what is sympathetically maintained pain
sensations of the CNS causes neuropathic-like pain in distribution of a sympathetic nerve
what is nociception
detection of noxious stimuli by specialised naked nerve endings in peripheral tissues
which fibres are responsible for nociception transmission
A delta fibres - in the skin, sharp and fast informative pain
C fibres - punishing pain
what other fibres can transmit pain
A alpha - efferent, motor, somatic, reflex activity
A beta- afferent, innervates muscle, touch and pressure
A gamma- efferent muscle
A delta - afferent pain, temperature and tissue damage
what are the 4 stages of nociception
detection
transmission
perception
modulation
what happens in detection of nociceptive pain
release of intracellular contents and mediators from trauma
activates nociceptive fibres which releases other substances that act on surrounding cells
- NGF - TrKA
- protons - ASIC
- ATP - P2X3
- capsaicin/endovanilloids/noxious heat - TRPV1
- bradykinin - B2 GPCR
- prostaglandins - prostanoid GPCR
cause depolarisation
how is nociception transmitted
- Nociceptive fibres enter dorsal horn – signal to brain via ascending pathway (5 subtypes of NaV channels involved in propagation)
- A delta fibres enter at laminae 1/5 (thalamus/brainstem)
- A beta fibres enter laminae 3,4 and 5
- C fibres enter at laminae 1 and 2
how is nociception processed
- Somatosensory cortex and thalamus processes information about the location and intensity of the signals
- Cognitive and affective aspects - cingulate and insular cortex, plus prefrontal cortex involved
- Amygdala in the limbic system - processes the emotional components
how is nociceptive pain modulated
- Changing transmission of pain impulses in spinal cord via complex Descending Modulatory Pain Pathways (DMPP)
excitatory or inhibitory
how is nociceptive pain transmission modulated excitatory
Central modulation- dorsal horn cells that are normally only activated by nociceptors start to respond to low-threshold afferents (innocuous peripheral stimuli evokes painful sensations)
Central sensitisation
1. Alteration in glutaminergic neurotransmission/NMDAR mediated hypersensitivity (spinal cord central sensitization is dependent on NMDA-mediated elevations of cytosolic Ca2+ in the postsynaptic neuron)
2. Loss of tonic inhibitory controls – enhances depolarisation and excitation or projection neurons
3. Glial-neuronal interactions - activated microglia release signalling molecules, including cytokines which enhance neuronal central sensitization and nerve injury induced persistent pain
how is nociceptive pain transmission modulated inhibitory
Gate control - Short inhibitory interneurons in the dorsal horn of the spinal cord modulate transmission at the first synapse.
* They mediate an inhibition of transmission (gate keepers).
* Enkephalins (endogenous opiates) are important neurotransmitters in this process
* Activation of inhibitory neurons in the dorsal horn stops this transmission
Descending inhibitory pathways from the brain – stimulates local inhibitory nerves to inhibit transmission
what are the 4 opioid GPCRs
delta
mu
kappa
orphan
