Pain and Analgesia Flashcards
What is the best definition of pain
An unpleasant sensory or emotional experience associated with actual or potential tissue damage, or described in terms of such damage
What are the two classes of pain
Nociceptive pain
Neuropathic pain
Describe how Nociceptive pain works and give examples of it
Peripheral visceral or somatic pain
Directe action of pain sensing receptors in response to noxious stimuli that alerts organic of impending tissue damage
Examples: Inflammation Fractures Burns Bumps and bruises
Describe how Neuropathic pain works and give examples of it
Pain produced by damage to dysfunction of nerves in peripheral or central nervous system
Examples: Nerve Trauma Peripheral neuropathy Phantom limb pain
What are the three processes of nociceptive pain
- Detection of pain in the periphery
- Transmission of pain signals from periphery to spinal cord- mainly by C fibres and Adelta fibres
- Reception of signals by higher central brain centers- afferent activity generates pain sensation that initates response
What is the function of A beta fibres
Touch and pressure (mechanoreceptors)
Target of TENS and acupuncture
What is the function of A delta fibres
Sharp pain (NOCICEPTORS)
Touch (Mechanoreceptors)
What is the function of C fibres
Dull and burning pain (NOCICEPTORS)
Touch (Mechanoreceptors)
Temperature (Thermoceptors)
What is the gate control pain theory
Formed of transmission neurones which supply the thalamus area of brain with sensory information
The neurones are affected by:
Small inhibitory neurones
Nociceptors (C and A delta fibres)
Mechanoreceptor (A Beta fibre) input
Describe the gate control pain theory (4 steps)
- Small inhibitory neurones (substantial gelantinosa SG interneurones) that inhibit and close the gate to reduce pain
- Activation of C and A-delta fibres open the gate and increase pain by direct excitation of the gate and inhibition of SG interneurones
- Activation of A beta fibres to close the gate- excitation of SG interneurones
- Descending inhibitory pathways from the CNS close the gate by:
Inhibition of the gate and direct activation of SG interneurones
What are the six inflammatory mediators of peripheral pain
- Bradykinin
- Substance P
- Adenosine Triphosphate (ATP)
- Protons (H+)
- Endogenous activators of TRPV1
- Prostanoids
Describe how bradykinin plays a part as an inflammatory mediator of peripheral pain
Made from vascular precursors and activates:
Beta 2 receptors: Nociceptive neurones
Beta 1 receptors: Metabolite unregulated via inflammation
Describe how Substance P plays a part as an inflammatory mediator of peripheral pain
Activates NKA (neurokinin) receptors in nociceptive pain
- Enhances NMDA action (hypersensitivity)
- CGRP peptide is co-released
Describe how Adenosine Triphosphate plays a part as an inflammatory mediator of peripheral pain
Activates P2X3 receptors
Describe how Protons (H+) plays a part as an inflammatory mediator of peripheral pain
Activates acid sensing ion channels (ASICS)
Describe how Endogenous activators of TPV1 vanillin receptors plays a part as an inflammatory mediator of peripheral pain
Heat
Target of capsaicin (API in chilli)
It is unregulated by BK and nerve growth factor
Describe how PROSTANOIDS plays a part as an inflammatory mediator of peripheral pain
Formed of prostaglandins and thromboxane
PGE2 and PGF2 are released in inflammation- greatly increased responses to bradykinin and 5-HT
Describe how GLUTAMATE plays a part as an inflammatory mediator of peripheral pain
Excitatory amino acid that acts at AMPA to mediate acute pain (fast response, baseline set)
NMDA receptor has delayed response
What are the two types of neuropathic pain and explain them
Sodium channel clustering- redistribution of sodium channels to areas of nerve damage can set up ectopic (out of place) firing
Sympathetic NS mediated pain- up regulation of alpha adrenoceptor means that noradrenaline release causes pain
What are the main drugs for nociceptive and neuropathic pain
Nociceptive pain:
Non opioid: paracetamol, aspirin, NSAIDS
OPIOID analgesics
Neuropathic pain:
Anti-deppresants
Anti-convulsants
Other CNS related drugs
What is the mechanism of action of aspirin and its role
Blocks cycloxygenase enzymes
COX-1 (constitutive form)
COX-2 (induced at damage sites) isoforms
Role:
Anti platelet effects (TXA2 effect)
Anti-pyretic (fever reducer)
Give examples of non selective NSAIDS
Indoles:
DICLOFENAC and Indomethacin
Propionic acid derivatives:
Ibuprofen
Naproxen
Ketoprofen
Give examples of COX-2 selective NSAIDS that were withdrawn
Rofecoxib and Valdecoxib- cardiovascular side effects
Give examples of COX-2 selective NSAIDS and their uses
Celecoxib and Etoricoxib
Licensed for Rheumatoid arthritis, osteoarthritis pain and gout
