pain physiology and treatment
DESCRIPTION
Pain, physiology, treatment, Nociceptor, Unpleasant sensory and emotional experience associated with actual or potential tissue damage, Central Sensitization, pathologic pain, physiologic pain, chronic pain, visceral pain, neuropathic pain, Opioids Local Anesthetics Non Steroidal Anti Inflammatory Drugs Alpha 2 adrenergic agonists NMDA Antagonists GABApentin TramadolTRANSCRIPT
PAIN: PHYSIOLOGY AND TREATMENT
Definitions
• Pain– “Unpleasant sensory and emotional experience
associated with actual or potential tissue damage or described in terms of such damage”.
• Nociceptor– is a receptor that is preferentially sensitive to a
noxious (damaging to tissue) stimulus or to a stimulus that would become noxious if prolonged.
Transduction
TransmissionModulation
Perception
Transduction
• Mechanical, chemical and thermal energy are converted into electrical energy/impulses by specialized nerve endings called “nociceptors”
• Nociceptors – free nerve endings of primary afferent fibers.– have high stimulus thresholds for activation.
Nociceptors
• A-fiber mechanoheat receptors
-signal “first” pain (sharp, stinging, pricking sensation), well localized pain, transient, lasts only as long as the stimulus activates the nociceptors
C-fiber mechanoheat (polymodal) receptors
-mediate “second” or “slow” pain, a diffuse, persistent sensation that exists past the termination of an acute painful stimulus.
Nociceptors
• Repeated stimulation produces:– reduction in receptor threshold – an enhanced magnitude of response.
Transmission
• occurs along 2 different types of afferent nerve fibers:A-delta fibers– large diameter– myelinated– rapid impulse conduction (6-30 m/sec)– stimulates immediate reaction
Transmission
• C fibers– small diameter– unmyelinated– slow conduction
• (0.5 – 2 m/sec)
– reinforces the immediate
response that is signaled by A-delta fibers
Transmission
• Spinothalamic tract– Most important tract in
transmission of nociceptive
information
• Spinoreticular tract
• Spinohypothalamic tract
Perception-Supraspinal Processing
• Reticular System
• Limbic System
• Thalamus
• Cortex
Transduction
TransmissionModulation
Perception
Descending Modulation
• Inhibitory influences at the
cortical and spinal cord levels
• Inhibitory neurotransmitters
include GABA, glycine,
serotonin, dopamine, NE,
endogenous opioids
Peripheral Sensitization
• arises as a result of the exposure of nociceptor to chemical mediators of inflammation: substance P, hydrogen ions, norepinephrine, bradydkinin, histamine, potassium, cytokines, serotonin, nitric oxide
• all of these mediators act together to lower the response threshold of both the A-delta and C fibers nociceptors
Central Sensitization• Produced by changes in the membrane
excitability of dorsal horn neurons. – Increase in receptive field of dorsal horn
neurons (zone of secondary hyperalgesia).– increased responsiveness to mechanical
stimulation that is normally innocuous (allodynia).
– Recruitment of non-nociceptive receptors (A-beta fibers)
Types of Pain
• Physiologic pain– transient stimulus, no tissue damage or
inflammation, neurophysiology associated with simple stimulus-response model.
Types of Pain
• Pathologic pain – pain that arises in the clinical setting
– involves dynamic changes in the processing of noxious input at both the peripheral and central levels
– stimulus is not transient
– usually associated with significant tissue inflammation.
– can be associated with damage to nervous tissue (neuropathic pain).
– recently occurring (acute) or long-lasting (chronic).
Acute Post-Operative Pain
• arises from soft tissue trauma or inflammation• plays a biologically adaptive role by facilitating
tissue repair– functions:
-hypersensitizes injured area (primary hyperalgesia)
-sensitizes surrounding tissues (secondary hyperalgesia)
– serves to facilitate avoidance of external stimuli
– doesn’t give license to allow pain to exist untreated
Chronic Pain:
• pain that persists beyond the expected time frame for a given disease, process or injury.
• may be associated with ongoing inflammation • may be autonomous with no temporal relation to
the inciting cause.• Maladaptive, offers no biologic advantage• examples of chronic pain:
– cancer pain– osteoarthritic pain– postamputation phantom limb pain
Visceral Pain
• nature of pain originating from viscera versus somatic tissues is significantly different.
• the viscera most sensitive to distention (hollow organs of GI tract), ischemia (myocardium) and inflammation (pancreatitis).
• poorly localized. • referred – pain response is localized to distant
structures
Neuropathic Pain• produced as a consequence of damage to the nervous
system.• characterized by altered sensory processing of stimuli• several manifestations of hypersensitivity:
– persistent burning sensations, partial or focal loss of sensitivity
• allodynia (an increased responsiveness to mechanical stimulation that is normally innocuous).
• may arise from an acute injury discharge in axotomized afferent fibers.
Systemic Response to Pain and Injury
• increased sympathetic tone– vasoconstriction– increased cardiac output through increases in
stroke volume and heart rate– decreased gastrointestinal and urinary tone– increased skeletal muscle tone
Systemic Response to Pain and Injury
• hormonal changes – increased secretion of cortisol, ADH, catecholamines,
renin, angiotensin II, aldosterone– decreases in insulin and testosterone
• endocrine changes result in a catabolic state:– hyperglycemia– increased protein catabolism and lipolysis, – renal retention of water and sodium, – increased potassium excretion– decreased GFR.
Stress Response Markers/Pain Assessment
• heart rate
• respiratory rate
• blood pressure
• posture
• attitude
• food and water intake
• patterns of defecation, urination
Stress Response Markers/Pain Assessment
• Change in activity levels
• Natural behaviors – inquisitive, grooming
• Provoked behavior
• Aggression
• Gait-/posture
• Vocalization
• Appearance of stereotypical behaviors
General Approaches to Pain Management
• minimize debilitating pathologic pain while maintaining the protective and adaptive aspects associated with physiologic pain.
• a single drug administered at a standard dose for different pain syndromes is not an effective pain management strategy.
General Approaches to Pain Management
• Pre-emptive analgesia-initiating treatment prior to acute insult helps to
limit the development of peripheral and central sensitization.
General Approaches to Pain Management
• Multimodal/balanced analgesia:– combining analgesic
drugs and techniques to achieve beneficial additive or synergistic analgesic effects.
– can use lower doses, fewer side effects.
General Classes of Analgesic Drugs
• 1. Opioids• 2. Local Anesthetics• 3. Non Steroidal Anti Inflammatory Drugs• 4. Alpha 2 adrenergic agonists• 5. NMDA Antagonists• 6. Others
• GABApentin• Tramadol
OPIOID ANALGESICS
USES
• 1. sedation• 2. analgesia• a. preoperatively• b. intraoperatively• c. postoperatively• 3. neuroleptanalgesia• a. in combination with a
tranquilizer/sedative• b. useful for minor procedures that do
not require general anesthesia
Opioid Classification
• Agonists– Stimulate receptor activity– Mu agonists
• most common group of opioid agonists used
• Include morphine, meperidine, oxymorphone, hydromorphone, fentanyl, carfentanil
Opioid Classification
• Agonists-Antagonists– Stimulate activity at some receptors and
antagonize others– Butorphanol – kappa agonist, mu antagonist
Opioid Classification
• Partial Agonists– Bind to receptor but only produce a partial
effect• Buprenorphine – partial mu agonist, kappa
antagonist
Opioid Classification
• Antagonists– Primary activity is mu receptor antagonism
• Naloxone
• Naltrexone
• Nalmefene
• Diprenorphine
• Classification:– Traditional:
• μ, κ, δ, ε, σ
– New (?) Classification: • OP1 (δ), OP2 (κ), OP3 (μ)
Opioid Receptor Pharmacology
Opioid Receptor Pharmacology
• Mu– Supraspinal, spinal, peripheral analgesia– Respiratory depression– Euphoria/Sedation– Physical dependence– Bradycardia
Opioid Receptor Pharmacology
• Kappa– Spinal analgesia
– Sedation
– Respiratory depression
• Sigma (opioid receptor?)– Dysphoria/hallucinations
– Hypertonia
– Respiratory stimulation
– tachycardia
Opioid Effects
• Cardiovascular– Bradycardia – vagally mediated– Negligible effect on myocardial contractility– Hypotension due to histamine release
• Seen with morphine, meperidine (particularly when administered IV)
• Not a problem with synthetic opioids
Opioid Effects
• Respiratory– Decrease in frequency and tidal volume– Blunts response to carbon dioxide– Cough suppressant
Opioid Effects
• CNS – Narcosis – sedation, euphoria, hypnosis, analgesia,
excitement, dysphoria– Medullary depression
• Respiratory center• Cough center• Vomiting center (delayed)
– Vomiting center (early)– Vagus nerve– Oculomotor nerve (miosis – dog; mydriasis – horse,
cat)
Opioid Effects
• Gastrointestinal– Salivation– Nausea– Vomiting– Nonpropulsive hypermotility– Defecation
Opioid Effects
• Species Specific Effects– Excitement in horses (u agonists;
agonists/antagonists)– Excitement in cats (dose related)– Panting in dogs – resets thermostat– Sweating in horses
Opioid Pharmacology:Distribution
Routes of Administration
• SC, IM, IV
• CRI
• Oral
• Epidural
• Transdermal
• Intra-articular
Epidural Catheter
Epidural Catheter
Commonly Used Opioids
Mu agonists
DRUG DOSE (MG/KG)
ROUTE
DURATION
COST (20 KG)
Morphine 0.5 – 1
IM/SC
4-6 0.27
Meperidine 2 –6
IM/SC
1-2 1.47
Fentanyl .004-0.008
IV/IM/SC
1-2 4.80
Oxymorphone 0.05-0.2
IV/IM/SC
4-6 14.00
Hydromorphone 0.1-0.2
IV/IM/SC
4-6 0.76
Commonly Used Opioids
Mixed agonists/antagonists
DRUG DOSE (MG/KG)
ROUTE
DURATION
Butorphanol 0.2-0.4
IV/IM/SC
3-4
Buprenorphine 0.01-0.02
IV/IM/SC/PO
8-12
Reversal of Opioid Effects
• Naloxone (1 ug/kg diluted in 5-10 ml normal)
• Butorphanol (0.1-0.2 mg/kg)
Which Opioid? Which Route of Administration?
• Nature of procedure – severity and expected duration of pain.
• Nature of patient
• Resources
Neuroleptanalgesia
• A state of quiescence, altered awareness and analgesia produced by the administration of an opioid analgesic and a tranquilizer or sedative
• Indications:– Minor surgical procedures
– Diagnostic procedures
– Premedication for General Anesthesia
– Induction of General Anesthesia
Neuroleptanalgesia
• Clinical Effects– Narcosis without unconsciousness– Hyper-responsive to auditory stimuli– Defecation– Respiratory depression– Bradycardia– Analgesia
Neuroleptanalgesia
• Combinations:
Acepromazine
Midazolam
Diazepam
Oxymorphone
Hydromorphone
Butorphanol
Morphine
Buprenorphine
Fentanyl