Pain Physiology and Mechanisms Animal Medicine 1 chapter 8

Pain

• Pain is a complex phenomenon, an aversive sensory and emotional experience
• It elicits protective motor actions, resulting in learned avoidance
• It may modify species-specific behavioral traits

Physiology of Pain

• Nociception is the detection by the nervous system of the potential for, or actual tissue injury
  • It protects the animal from painful or noxious stimuli
• Physiologic pain (adaptive) is "ouch" pain with little or no tissue injury
• Pathologic pain follows tissue injury and can be acute or chronic

Pathologic Pain

• Classified based on mechanism: inflammatory, neuropathic, cancer, idiopathic
• Classified based on origin: visceral or somatic (superficial or deep)
• Classified based on severity of pain: none, mild, moderate, severe

Nociception: The Pain Pathway

• Step 1: Transduction: transformation of stimuli into sensory electrical signals (action potentials)
• Step 2: Transmission: sensory impulses conducted to the spinal cord
• Step 3: Modulation: impulses are either amplified or suppressed
• Step 4: Perception: impulses are transmitted to the brain where they are processed and recognized
• Each step has different receptors
• Drugs can be selected that will target specific receptors and block a specific step
  • Multimodal therapy: targeting two or more receptors

Consequences of Untreated Pain

• Catabolism and wasting
• Immune system suppression
• Inflammation and delayed wound healing
• Anesthetic risk and increased anesthesia doses
• Patient suffering

Primary Hyperalgesia

• Peripheral hypersensitivity
• Results from tissue damage and constant stimulation of nerves
• Area close to the site of tissue injury becomes painful when stimulated with non-noxious stimuli

Secondary Hyperalgesia

• Chronic pain
• Central nervous system hypersensitivity or “windup”
• Area of hypersensitivity is further away from the site of tissue injury
• Results from constant stimulation of spinal cord neurons
• Neurons become hyperexcitable and sensitive

Physiologic Changes Caused by Pain

• Hypertension
• Tachycardia, tacharrhythmia
• Peripheral vasoconstriction (pale mucosae)
• Tachypnea
• Shallow breathing
• Exaggerated abdominal component
• Panting (dogs)
• Open-mouthed breathing (cats)
• Mydriasis

Signs of Pain in Animals

• Pain elicits a stress response
• Stress-related pain results in “fight-or-flight” physiological response

Preemptive Analgesia

• Administration of pain medication before the pain occurs
• Commonly involves adding analgesic to premedication before anesthesia
• Reduces overall requirement for analgesia and duration of administration
• Prevents windup

Behavioral Responses to Pain

• Vary depending on species, age, breed, and temperament
  • Young patients less tolerant
  • Cattle very stoic
  • Large dog breeds more stoic than small toy breeds
  • Cats hide; dogs seek owner comfort; herd animals separate themselves
• Vary depending on nature, duration, and severity of pain and presence of humans

Physical Evidence of Pain

• Changes in gait and level of activity
  • Evidence of arthritic pain
• Reluctance to lie down or constantly shifting position
  • Evidence of thoracic or abdominal pain
• Vocalization
• Changes in facial expressions, appearance, and attitude

Pain Assessment Tools

• Simple descriptive scales
• Visual analogue scales
• Numeric rating scales
• CSU Canine Acute Pain Scale and CSU Feline Acute Pain Scale
• Categorical numeric rating scale
• Validated
• Feline Grimace Scale
• Chronic Pain Assessment

Assessing Response to Therapy

• Acute surgical pain vs chronic pain

Nature of Pain

• Pain is a complex phenomenon
• A protective mechanism
• Can modify species-specific behavior traits

Physiology of Pain

• Nociception - detection of potential or actual tissue injury
• Physiologic pain is adaptive and occurs with little or no tissue injury
• Pathologic pain is linked to tissue injury and can be acute or chronic

Pathologic Pain Classification

• Inflammatory, neuropathic, cancer, idiopathic based on mechanism
• Visceral or somatic based on origin
• None, mild, moderate, severe based on severity

Nociception: The Pain Pathway

• Transduction: Stimuli transformed into sensory electrical signals
• Transmission: Sensory impulses conducted to the spinal cord
• Modulation: Impulses are amplified or suppressed
• Perception: Impulses are transmitted to the brain for processing and recognition
• Each step involves different receptors, allowing for targeted drug therapy

Multimodal Therapy

• Targeting two or more receptors in the pain pathway to manage pain

Consequences of Untreated Pain

• Catabolism and wasting
• Immune system suppression
• Inflammation and delayed wound healing
• Increased anesthetic risk and dosage
• Suffering

Primary Hyperalgesia

• Peripheral hypersensitivity due to tissue damage and nerve stimulation
• Area adjacent to the injury becomes sensitive to non-noxious stimuli

Secondary Hyperalgesia

• Central nervous system hypersensitivity or "windup"
• Area of hypersensitivity is distant from the site of injury
• Spinal cord neurons become hyperexcitable and sensitive

Pain-Induced Physiologic Changes

• Hypertension
• Tachycardia and tacharrhythmia
• Peripheral vasoconstriction
• Tachypnea
• Shallow breathing
• Exaggerated abdominal breathing
• Panting (dogs)
• Open-mouthed breathing (cats)
• Mydriasis

Behavioral Responses to Pain

• Vary based on species, age, breed, temperament, pain nature, duration, severity, human presence
• Stressed response leading to "fight-or-flight"

Physical Evidence of Pain

• Changes in gait and activity level, especially indicating arthritic pain
• Reluctance to lie down or constant shifting - thoracic or abdominal pain
• Vocalization
• Altered facial expressions, appearance, and attitude

Preemptive Analgesia

• Administering pain medication before pain occurs
• Often used as part of premedication before anesthesia
• Reduces overall analgesic needs and duration, prevents windup

Pain Assessment Tools

• Simple descriptive scales
• Visual analogue scales
• Numeric rating scales
• CSU Canine Acute Pain Scale and CSU Feline Acute Pain Scale
• Categorical numeric rating scale
• Validated Feline Grimace Scale
• Chronic Pain Assessment

Assessing Response to Therapy

• Hourly for acute surgical pain, monthly for chronic pain
• Pain-associated behaviors should recede with effective analgesia
• Pain assessment scores should decrease

Analgesic Administration Routes

• Intravenous
• Intramuscular
• Subcutaneous
• Oral
• Transdermal
• Epidural
• Intraarticular

Opioid Analgesics

• Vary in potency, duration, and adverse effects
• Injectable premedication often combined with tranquilizers
• Induce sedation at higher doses
• Postoperative analgesia
• Sedative/antianxiety effects
• Gastrointestinal effects: initial increased activity, followed by slowdown
• Metabolized in the liver

Opioid Agents: Morphine

• Used for moderate to severe visceral or somatic pain
• Can cause excitement or dysphoria in cats and horses
• Administered intravenously, intramuscularly, subcutaneously, intraarticularly, epidurally, spinally
• Adverse effects: Gastrointestinal stimulation, ileus, colic, excitement, miosis, mydriasis, hypothermia, hyperthermia, bradycardia, panting, increased intraocular pressure, urinary retention

Opioid Agents: Hydromorphone

• Greater potency than morphine with similar duration of effect
• Administered intravenously, intramuscularly, subcutaneously

Opioid Agents: Methadone

• Synthetic opioid with similar characteristics to oxymorphone and hydromorphone
• Less likely to cause vomiting in cats and dogs

Opioid Agents: Fentanyl

• One of the most potent analgesics
• Rapid onset, short duration when administered intravenously
• Continuous intravenous drip, transdermal patch, intramuscular, subcutaneous, or epidural injection

Opioid Agents: Buprenorphine

• Partial mu agonist with delayed onset and longer duration
• Can be used to reverse effects of morphine and fentanyl
• Expensive Schedule III drug

Opioid Agents: Butorphanol

• Synthetic opioid with agonist and antagonist properties
• Used as preanesthetic, sedative, and postoperative visceral analgesic
• Administered intravenously, intramuscularly, subcutaneously, and orally
• Schedule IV drug

Opioid Agents: Nalbuphine

• Kappa agonist and mu antagonist
• Weak analgesic and sedative
• Used as a reversal agent for opioid agonists

Opioids: Postoperative Analgesics

• Administered intramuscularly or subcutaneously before consciousness returns
• Short duration of action
• Potential adverse reactions: Respiratory depression, bradycardia, excitement, apprehension, hypersalivation, mydriasis, excessive sedation, panting, increased sensitivity to sound, urinary retention, gastrointestinal effects

Opioids: Intravenous Infusion

• Provides continuous analgesia for constant pain

Opioids: Intraarticular Injection

• Used after elbow or stifle surgery
• Provides 8 to 10 hours of postoperative analgesia

Opioids: Epidural Injection

• Instilled into epidural space at the lumbosacral junction
• Provides analgesia to hind limbs, abdomen, caudal thorax, pelvis, tail
• Morphine is most commonly used

Opioids: Transdermal Use

• Fentanyl transdermal patch provides convenient, long-term opioid administration

Nonsteroidal Antiinflammatory Drugs (NSAIDs)

• Inhibit prostaglandin synthesis by inactivating COX isoenzymes
• Metabolized in the liver, eliminated by kidneys and gastrointestinal tract
• Onset of action: 30 to 60 minutes
• Duration of effect varies with species
• Toxicity varies with species

Adverse Effects of NSAIDs

• Inhibit production of beneficial prostaglandins
• COX-2 selective NSAIDs cause fewer adverse effects
• Stomach ulcers, vomiting, gastrointestinal bleeding, lack of appetite
• Gastrointestinal ulceration
• Renal toxicity
• Impaired platelet aggregation
• Liver damage
• Antagonist to drugs for cardiac disease and hypertension

Local Anesthetics as Analgesics

• Advantages: Complete anesthesia of affected area, low toxicity, rapid onset of action
• Disadvantages: Short duration of action, central nervous system and cardiac toxicity with repeated use

Alpha2-Adrenoceptor Agonists

• Limited use in small animals due to adverse effects
• Used in horses to provide sedation, muscle relaxation, and analgesia
• Adverse effects: Cardiovascular, respiratory, GI

Ketamine

• Adjunct to other potent analgesics
• Blocks NMDA at the level of the spinal cord to prevent windup

Gabapentin

• Anticonvulsant that treats neuropathic pain and hypersensitivity
• Useful in dogs and cats for chronic pain
• Few adverse effects, except drowsiness

Amantadine

• NMDA receptor antagonist
• Useful for neuropathic pain and central hypersensitivity

Corticosteroids

• Strong antiinflammatory properties
• Adverse effects: Ulcerogenic, immunosuppression, hyperadrenocorticism

Tramadol

• Nonopiate drug with activity at the mu receptor
• Oral administration after patient has resumed eating
• Don't use concurrently with other norepinephrine or serotonin reuptake inhibitors

Tranquilizers

• Not analgesics but can potentiate opioid effects

Other Analgesic Adjuncts

• Antidepressants
• Antianxiety
• Bisphosphonates

Multimodal Therapy

• Combination of analgesic drugs targeting different pain pathway mechanisms

Examples of Multimodal Therapy

• Acetaminophen and codeine
• Fentanyl and meloxicam
• Morphine and injectable NSAID
• MLK

Home Analgesia

• Fentanyl patches for chronic pain
• NSAIDs for long-term therapy of chronic painful conditions
• Oral morphine
• Tylenol with codeine
• Tramadol

Nursing Care for Relieving Discomfort

• Keeping the patient and environment clean and dry
• Comfortable bedding and quiet surroundings
• Opportunity to urinate and defecate
• Comfortable position
• Reducing anxiety with familiar items
• Ophthalmic ointment for unconscious patients
• Touch and reassurance

Nonpharmacologic Therapies

• Used in conjunction with or as adjunct to pharmacological therapy
• Acupuncture
• Transcutaneous electric nerve stimulation
• Massage therapy
• Heat or cold application
• Physiotherapy
• Laser or magnetic therapy
• Homeopathic or herbal remedies