APPP 16: Pain Flashcards
What are the 2 anatomical classifications of pain?
- somatic pain: pain that originates in peripheral tissues such as skin, bone, muscles, tendons, or ligaments
- visceral pain: originates in body’s internal organs (ie. heart, intestines, appendix, kidneys)
What are the 3 classifications of pain by duration?
- acute
- episodic: may occur at irregular intervals
- chronic: lasts for 3+ months or beyond expected healing time, can sometimes occur for no known reason
What are the 3 classifications of pain by mechanism?
- nociceptive pain
- neuropathic
- nociplastic pain
What is nociceptive pain?
caused by tissue damage and/or inflammation
- sensation can be sharp, pricking, dull, or aching
- ie. paper cut, infection, broken bone
What is neuropathic pain?
caused by nerve damage due to injury or disease
- burning, tingling, shooting, or like electric shocks
- ie. diabetic neuropathy, shingles, sciatica
What is nociplastic pain?
caused by changes in how the nervous system processes pain
- not linked with a clear injury, tissue damage, inflammation, or disease
- sensations related to this kind of pain vary widely
- ie. fibromyalgia, complex regional pain syndrome
Psychological Effects of Pain
What are the physical effects of pain? (3)
- fatigue and sleep disturbances
- inability to keep up with daily activities
- adverse side effects of medications
Psychological Effects of Pain
What are the psychological effects of pain? (3)
- mood swings
- irrational thinking or behaviour
- helplessness
Functional Effects of Pain
What are the effects of pain on the brain? (2)
- anxiety, fear, depression
- inhibition or promotion of pain
Functional Effects of Pain
What are the effects of pain on the cardiovascular system? (2)
- increased heart rate and blood pressure
- water retention
Functional Effects of Pain
What are the effects of pain on the gastrointestinal system? (2)
- nausea and vomiting
- constipation
Functional Effects of Pain
What are the effects of pain on the respiratory system? (2)
- increased respiratory rate
- increased risk for infection
What are the 4 processes for modulation of pain sensation?
- transduction
- transmission
- perception
- modulation
What is transduction?
nociceptors detect noxious stimuli from somatic and visceral tissues (mechanical, chemical, etc.)
- painful stimuli is converted to energy (neuronal action potential)
- stimulus sends an impulse across peripheral nerve fibres
What are the types of nociceptors involved in transduction? (3)
- mechanical nociceptors
- thermal nociceptors
- chemically sensitive nociceptors
What are mechanical nociceptors?
- high threshold mechanoreceptors
- respond to strong mechanical stimulation (ie. pinching, pressure) – Piezo2: mechanically-activated ion channel crucial for touch and proprioception
- TRPA1: primarily known for its role in chemical nociception, can also be activated by mechanical stretch
What are thermal nociceptors?
- activated by skin temperatures above 42ºC or by severe cold
- TRPV1: activated about 42ºC, also sensitive to capsaicin and acidic conditions
- TRPM8: activated by cold temperatures below 25ºC
What are chemically sensitive nociceptors?
respond to various chemicals and environmental irritants
- prostaglandins: produced by cyclooxygenases acting on arachidonic acid
- bradykinin: forms from kininogen via kallikreins
- serotonin: releases from clotting platelets
- histamine: originates from mast cells and basophils
- cytokines (ie. TNF-a and IL-1b): emitted by immune cells
Transduction: Nociceptor Activation
What substances are involved in nociceptor activation? (7)
- globulin and protein kinases
- arachidonic acid
- histamine
- nerve growth factor (NGF)
- substance P (SP) and calcitonin gene-related peptide (CGRP)
- other substances
Transduction: Nociceptor Activation
Globulin and Protein Kinases
damaged tissue releases globulin and protein kinases
- ie. kallikrein cleaves kininogen to release bradykinin
Transduction: Nociceptor Activation
Arachidonic Acid
- released during tissue damage
- metabolized into prostaglandin and cytokines
- through G protein and protein kinase A cascade, prostaglandins block K+ outflow from nociceptors, increasing their sensitivity
Transduction: Nociceptor Activation
Histamine
- released from mast cells when tissue is damaged
- stimulates nociceptors
Transduction: Nociceptor Activation
Nerve Growth Factor (NGF)
- released during inflammation or tissue damage
- binds to TrkA receptors on nociceptors, activating them
Transduction: Nociceptor Activation
Substance P (SP) and Calcitonin Gene-Related Peptide (CGRP)
- released due to injury
- excite nociceptors
- both cause blood vessels to dilate, spreading swelling around the injury
Transduction: Nociceptor Activation
Other Substances
released during tissue damage:
- serotonin (5-HT)
- acetylcholine (ACh)
- low pH solutions
- ATP
Opioids
- opiates include natural plant alkaloids (ie. morphine, codeine, and many semisynthetic derivatives)
- opioid receptor in CNS is an endogenous opioid
- endogenous opioid peptides include enkephalins, endorphins, and dynorphins
What are the 2 common opiate agonists?
- morphine
- codeine
What is the common opiate antagonist?
naloxone
- affinity for all known opioid receptors
What are the 3 principle opioid receptors?
members of GPCR family
- μ (mu)
- Κ (kappa)
- 𝛿 (delta)
What does the activation of opioid receptors lead to? (3)
- reduced cAMP (and PKA activity) – coupled to inhibitory G-protein (Gi)
- reduce neuronal cell excitation and transmission – closing of voltage sensitive Ca2+ channels (decreased neurotransmitter release), and stimulation of K+ efflux (hyperpolarization)
- euphoria – involves dopaminergic pathways
What are the 2 pathways underlying rewarding properties of opiates?
- MOR (μ opioid receptor) agonists reduce excitability and transmitter release
- opiate-induced inhibition in ventral tegmental area (VTA) on GABAergic interneurons or in nucleus accumbens (NAc) reduce GABA-mediated inhibition and increase outflow from ventral pallidum (VP), which correlate with a positive reinforcing state (enhanced reward)
Non-opioid Analgesics
What is NSAID anti-inflammatory activity mediated by?
through inhibition of prostaglandin biosynthesis
Non-opioid Analgesics
What is paracetamol?
- one of the most widely used analgesics
- mechanism by which it elicits pain relief is not fully understood
- primarily COX-independent
- weak anti-inflammatory activity
- raises threshold to painful stimuli
Non-opioid Analgesics
What are topical analgesics?
relief of mild to moderate muscle and joint pain
- topical local anesthetics
What is transmission?
nociceptive message is transmitted to CNS of actual or impending tissue injury
- A-delta fibres send sharp, localized, and distinct sensations
- C fibres relay impulses that are poorly localized, burning, and persistent
What is perception?
person is aware of the pain
- somatosensory cortex identifies location and intensity
What is modulation?
modulation of pain (positively or negatively) by the body
- excitatory neurotransmitter (ie. glutamate, substance P, CGRP) mediate synaptic transmission in dorsal horn
- inhibitory neurotransmitters (ie. GABA, glycine, enkephalins, dynorphin, noradrenaline) work to hinder pain transmission