Anatomy and Physiology of Pain Flashcards
What is pain?
An unpleasant sensory and emotional experience
- there is NO WAY to be objective about quantifying it
- may not be proportional to tissue damage
- is PURELY an emotionally preceptive thing
What does it stimulate and retard?
- amplifies the stress response (sympathetic NS) to traumatic injury
- stimulates endocrine and metabolic systems
- retards patient’s recovery from trauma, surgery and disease
What is the difference between acute and chronic pain?
Acute pain: lasts longer than 6 months (subsides once the healing process has occurred)
Chronic Pain: involves complex processes and pathology. Involves altered anatomy and neural pathways. Lasts longer than 6 mo (causes re-wiring of the spinal nerves)
Why do we want to be quick about treating pain?
Tissue damage has the potential to elicit mechanisms that can create disabling situations that may outlast the period of healing
Cousin’s Theory of Pathophysiology of Acute Pain
-that sever, unrelieved pain can result in abnormally enhances physiological responses that lead to progressively increased pathophysiology
What are the harmful organ effects of pain?
- there is increased adrenergic stimulation (SNS)
- increase the heart rate
- increase cardiac output
- increase myocardial oxygen consumption
- decreases pulmonary vital capacity
- decreases alveolar ventilation
- decreases functional residual capacity
- atrial hypoxemia
- suppression of immune functions, predisposing trauma patients to wound infections and sepsis
What is chronic pain syndrome?
- pain is the focus of life
- sometimes the result of acute, unrelieved pain, sometimes from a near-muscular disorder like fibromyalgia or MS
Why is it so important that pain is not left without tx for a few weeks?
- a person with severe pain that does not treat their pain symptoms will re-wire their pain signals and will experience pain in the absence of any major stimulation for the rest of their lives
What are the receptors of pain?
free nerve endings
What are the different ways that nerves can be stimulated to elicit a pain response?
- through mechanical damage, extreme temperature, or chemical irritation
What are the 2 types of neurons involved in pain?
- A delta: first pain, sharp (protective pain)
- C: second pain, dull (learning and behavioural pain)
What are the 4 processes involved in pain stimulation?
Define each
- transduction: local biochemical changes in nerves endings that generate a signal
- transmission: movement of that signal from the site of pain in the spinal cord and the brain
- modulation: endogenous systems in place that can inhibit pain at any point along the pathway
- perception: synthesis and analysis in the brain
What are nociceptors?
- free nerve endings with the capacity to distinguish between noxious and innocuous stimuli
- when exposed to mechanical, thermal or chemical stimuli, tissue damage occurs
- substances are released by the damaged tissue which facilitate the movement if pain impulse to the spinal cord
What are some of the substances released from traumatized tissues that cause pain? What do they do?
- bradykinin
- serotonin
- substance P
- histamine-> inflammation and exacerbation
- prostaglandin -> target of NSAIDs
- – these cause cell depolarization by sodium flux
How do NSAIDs reduce pain?
Corticosteroids?
because they minimize production of prostaglandin
What is the transmission pathway of pain in the body?
initial damage -> nerve-> spinal cord -> thalamus -> central structures of the brain where pain is processed
- transmission of pain requires NT (opioids inhibit the release of NT)
Describe A delta fibers
Fast pain
large diameter fibers (2-5 uM) and allow the pain signal to be transferred very fast
- causes the body to withdraw immediately from a painful stimulus-protective
Describe slow pain
- pain stars more slowly
- transmitted by small diameter (0.2-1 uM)
- signal travels at a speed of less than 2/s
- body response: immobilization (guarding, spasm or rigidity) Healing and behaviour modification learning
Explain what is necessary for the perception of pain?
- cortical structures (higher functioning)
- there is no pain without relatively large cortical structures and the ability to generate emotional responses
- vertebrates
What does modulation do in the pain response?
- this list he portion of the pain system that reduces the pain sensation
- mediated by endorphins (endogenous opioids). Both descending fibres in the spinal tract and higher cordial enters release endorphins to modulate both transmission and perception
- in addition, central NT such as serotonin modulate perception. This explains why antidepressants can decrease pain
How do endorphins work as natural endorphins?
- released from their storage areas in the brain
- when a pain impulse reaches the brain - they bind to receptors in the pain pathway to block transmission and perception of pain
What can activate the descending pain modulation system?
STRESS- modulates pain and causes you to not feel it
What drugs alter the perception of pain?
parenteral opioids, a2 agonists, general anesthetics
What drugs alter the transmission of pain?
local anesthetics - peripheral nerve, plexus, epidural block
What drugs alter the modulation of pain?
spinal opioids, a2 agonist, NMDA receptor antagonists, NSAIDS, anticholinesterases, CCK antagonists, NO inhibitors, potassium channel openers
What drugs alter the transduction of pain?
NSAIDS, antihistamines, membrane stabilizing agents, local anesthetic, opioids, bradykinin and serotonin antagonists
What is the gate control theory?
- physiological and psychological interactions
- suggest spinal gates in the dorsal form at each segment of the spinal cord
- competition at each gate for heat, touch or pain to be transmitted at each point
What are the categories of pain?
- Nociceptic: injury, trauma, and infection
- Neuropathic: damage or dysfunction of the peripheral or CNS
- Visceral: arising from an internal organ - myocardial infarction, appendicitis, small bowel obstruction
What is hyperalgesia?
intense pain in response to a mildly painful stimulus
What is allodynia?
Pain in response to completely innocuous stimulus (touch)
What is neuropathic pain?
- abnormal processing of the impulsed either by the peripheral or central nervous system
- may be caused by injury, scar tissue from surgery, nerve entrapment, or damaged nerves
- IT IS NOT TOTALLY UNKNOWN IN ALL CASES
What effects do NSAIDs have? (3)
analgesic, antipyretic, anti-inflammatory (these effects are all caused by inhibition go prostaglandins)
What are the 3 COX enzymes?
COX 1- non-inducible, found in many cell types constitutively.
- this isoform has critical functions, such as maintaining the stomach lining
COX 2- the form induced in immune cells
- this isoform is responsible for pain, inflammation and fever
COX 3- highest content in brain and heart
What are the 3 phases of inflammation?
- acute transient phase (local vasodilation, increased capillary permeability)
- delayed subacute phase (infiltration of leukocytes and phagocytes)
- chronic proliferative phase (tissue degeneration and fibrosis)
When are prostaglandins released by a cell?
Released following cell damage - cause pus and inflammation
What is a fever caused by?
- set point regulated by the hypothalamus - dedicated balance between heat loss and production
- caused by: infection, tissue damage, inflammation, graft rejection, malignancy
- release of prostaglandins near hypothalamus under these conditions induces fever
- NSAIDs reduce fever, but do not reduce increased body temp due to exercise/ambient heat
How to prostaglandins induce pain?
- they induce pain by stimulating the local pain fibres
- inflammation also induces hyperalgesia
- NSAIDs can actually be superior to opioids for inflammation induced pain
What are some other effects of prostaglandins?
- platelet aggregation and formation of clots (accounts for coronary benefits of ASA)
- PGs are important in modulating stomach acidity and mucous lining (accounts for all the GI side effects of NSAIDs)
- PGs are important for uterine contraction- may account for some cases of dysmenorrhea
What are the two mechanisms of action of ASA?
- ASA irreversibly acetylates COX enzymes, thus this effect lasts as long as it takes to replace the enzyme (not dependent upon aspirin elimination)
- metabolite of ASA, gentisic acid, is a competitive inhibitory of COX enzymes, thus this effect depends upon clearance
How does caffeine act as a coanalgesic?
- caffeine increases the analgesic effect of all nonopioid analgesic drug - the cause of the effect is unknown (may be due to cortical vasoconstriction)
- the required dose is 60-120 mg - most preps have less than this however
- ingesting foods and beverages with caffeine also contributes to coanalgesic effects
What is the most effective way to take acetaminophen or ibuprofen?
- take the max amount with a coffee as well as a glass of ice water
- ice water causes the stomach contents to dump into the intestine- increases the absorption rate
What can contribute to a salicylate overdose?
- 10-30 g dose can cause fatality
- pepto-bismol can cause salicylate toxicity
- salicylate is also found in acetaminophen
What are the signs and symptoms of salicylate overdose?
- tinnitus
- marked increase in metabolic waste
- intital hyerventilation- due to futile cycle burning of O2, overproduction of CO2
- metabolic acidosis- overproduction of CO2
- severe hypoglycemia - futile cycle uses up all the glucose
What is the treatment of a salicylate overdose?
- treat with parenteral fluids and glucose
- parenteral sodium bicarbonate solution
- acetazolimide
- activated charcoal
What are the immediate dangers of salicylate overdose?
- hyperthermia, dehydration and hypoglycemia
NSAID classes?
- salicylates: methylsalicylate- oil of wintergreen. Bismuth salicylate, asa
- proprionic acid
- ibuprofen
- - generally similar effects to other non similar COX inhibitors
- - generally less GI side effects (but still major problem)
- naproxen
- - naproxen have a half like of 12 -18 hours, effective from 2-12 hours. Naproxen peaks within 1 hour. Can only be dosed 2x daily! - Diclofenac
- high potency but also have a higher GI bleed risk
- prescription only! Used for inflammatory pain, such as arthritis, post op swelling, gout. Sometimes endometriosis
- in gel, used for muscular/joint pain (tennis elbow, muscle, low back pain) - Indomethicin
- specifically used for gout pain and swelling
- less common for chronic conditions than diclofenac
When do GI symptoms typically arise?
- primary problem with no-selective COX inhibitors
- PGE2 and PGI2(products of COX-1) are made by the gastric mucosa. These PGs suppress acid production, increase gastric blood flow and increases the secretion of mucin
- inhibition of COX-1 thus increases acid production and decreases mucous protection, inc addition to local effects of drugs
What is misoprostol?
prostaglandin analog
- used to supply the stomach with PG effect lost with non-selective COX inhibitors
- adverse effects and effectiveness - around 1% risk prevention, 15% induction of diarrhea
What are the main adverse effects and drug interactions associated with NSAIDS?
- Reye’s syndrome - fatal hepatic encephalopathy in children with viral infection- associated with SAS - chicken pox and influenza
- Hypertension and Angina
increase in circulating blood volume - Bleeding disorders- inhibition of cyclooxygenase, alcohol, warfarin and rofecoxib
Inhibition of which COX enzyme causes the most side effects?
inhibition of COX1
What do the analgesic antipyretic and anti-inflammatory effects primarily arise from? (which COX enzyme?)
COX2
- looking for COX 2 selective inhibitors now because of this
Why is acetaminophen the DOC in children?
Because of Reye’s syndrome
What is the MOA of acetaminophen overdose?
- a minor clearance pathway for a highly reactive metabolite of acetaminophen at low doses is through glutathione in the liver. GSH is a critical antioxidant. At high doses, this reactive depletes GSH
- this causes oxidative damage to liver cells from loss of anti-oxidant and direct damage to liver cells from the highly reactive intermediate
What are the signs and symptoms associated with acetaminophen overdose?
- severly elevated serum transaminase levels
- hepatic encephalopathy
- jaundice- by the time this is reached tx is too late
What would you do if you found a child with an empty tylenol bottle on the ground around him?
- pump the stomach and give a glutathione treatment
Management of acute migraines
- often NSAIDs will be effective and should be tried first
- combination of acetaminophen, acetylsalicylic acid and caffeine may be effective
- occasionally opioid drugs may be used to treat refractory migraine headaches but should always be last resort
What else can be used to treat acute headaches?
- ergot alkaloids
- ergotamine, dihydroergotamine
- postulated mechanism of action- nonspecific serotonin agonists
- side effects most often related to arteriolar constriction
- coanalgesic with caffeine
What are the cautions that could be used with ergot alkaloids?
- liver disease
- rebound headache with frequent use
- cardiovascular disease- causes arteriolar vasoconstriction
- poor peripheral circulation
What else can be used to treat an acute headache?
- can use the triptans
(sumatriptan, naratriptan, risatriptan, zolmitriptan) - postulated MOA: agonist at the serotonin receptor
- side effects similar to ergot alkaloids
How do the triptans work to treat a migraine headache?
- these are serotonin receptor agonists
- very effective for migraines but also very expensive
- usually relieve nausea as well as headaches
What is the caution associated with triptans?
- the concurrent MAOI or SSRI antidepressants - when used in conjunction with triptans can cause serotonin syndrome - akathisia like restlessness, muscle twitches, myoclonus, hyperreflexia, sweating, shivering and tremor - can possibly lead to seizures and coma
- NOT to be used concurrently with ergot alkaloids
What can be used for migraine prophylaxis?
- propanolol and other B blockers can be used as a preventative treatment
- – regulates blood flow, reduces blood pressure
- – side effects are: tiredness, dizziness, dec libido, dream effects and can exacerbate asthma
- amitryptiline
- – much lower doses than is used for depression
- – side effects: dry mouth and eyes, drowsiness
- Gabapentin
- – modulated GABA receptors
- Candesartan
- – angiotensin II receptor antagonist, reduces blood pressure
