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The Physiology Of Pain
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The Physiology Of Pain


Understanding the pain pathway is the first step to effective pain management in veterinary patients.

Understanding the pain pathway is the first step to effective pain management in veterinary patients.

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  • What is pain? We’ve all experienced it, some of us may be experiencing it right now, but how is pain defined? Pain is complex, it is both sensory and emotional and can be actual or potential. Just thinking about chewing on a cactus elicits a visceral reaction that can be considered pain.
  • Pain is often over looked, even in human medicine. It wasn’t until the year 2000 that the joint commission on accreditation of healthcare organizations (which is a mandatory regulatory agency) began mandating that pain be elevated to the 5 th vital sign along with Temp, pulse, resp, and BP. In 2003, AAHA (which is a volunteer regulatory agency) followed suit by elevating pain to the 4 th vital sign along side temp, pulse, and resp.
  • So, noxious stimuli is what we call something that can trigger that nervous system activity. Pain implies noxious stimuli that has been perceived at the cortical level, or in the brain. Noxious stimuli can be chemical like chemotherapeutics, or ketamine, mechanical like a toe pinch or orthopedic exam, or thermal like frostbite or burns. Some nociceptors respond to one type of noxious stimuli, some to all 3 types. So, a quick review of language, A nociceptor is a receptor that detects painful or noxious stimuli and nociception is the activity that that stimuli produces within the nervous system. And pain is the perception of that painful signal.
  • To help define pain, you need to understand the language. A nociceptor is a receptor whose job is to detect tissue damaging or painful stimuli. Nociception is what we call the activity in the nervous system that is produced by a painful situation. When your scalpel cuts skin, that stimulation initiates activity in the nervous system- this is called nociception; the journey of the pain signal.
  • Stress is also important to consider because it can exacerbate pain thru modification of the nervous system in response to tension. Stress can be a result of pain from surgery or trauma, it can be due to external stressors like severe weather, a trip to the vet, owner on vacation or internal stressors like the physiologic changes that result from a disease process that is stressing the body like diabetes or cancer.
  • There is a pathway that pain takes on its way to the brain. This is important because it helps us decide our treatment options. Pain starts with a noxious or painful stimulus that is translated into electrical activity at the sight of injury. That energy is converted into a signal that the nervous system can understand, this is called transduction and it is the first step towards perception of pain
  • This signal travels along the nerve fibers- acute pain takes the fast, myelinated a-delta tract, and chronic pain takes the slow, unmyelinated c-fiber tract. this is called transmission because the pain signal is transmitted from the sight of injury to the spinal cord
  • Once at the spinal cord, the signal is modulated meaning it either produces a reflex, or becomes modified by endogenous systems within the spinal cord (like serotonergic, noradrenergic, opioid), and then gets sent to higher levels of the CNS to be perceived. Our opioids help modulate nociception by decreasing the intensity of the signal that is sent up to the brain.
  • As you can see here, injury signals enter the spinal cord. Considerable processing of painful stimuli occurs in the dorsal horn but exactly what happens here is still up for debate.
  • Perception is the final stop on the pain train and it is the successful transduction, transmission, and modulation of noxious stimuli. It is also conscious subjective and emotional
  • The best way to control pain, is to treat it along varying points of the pathway. Drugs that affect the transduction of noxious stimuli are those that will change the signal locals anesthetics which block the sodium channels that are necessary for nerve impulse transmission work at this level and are an easy and inexpensive way to augment a systemic pain management plan. They are capable of blocking both sensory and motor impulses.
  • NSAIDs also work at this level because they inhibit the production of prostaglandins which are responsible for inflammation and pain. NSAIDS work best when given pre-emptively or before the insult occurs, which we have control over in a surgical situation, but not in a trauma situation. NSAIDS are not good for visceral pain with the exception of banamine in horses.
  • A simple bit about NSAIDS… Many NSAIDS are classified as cox-1 or cox-2 specific. Cox being short for cyclooxygenase. The more cox2 specific (meaning specific for blocking the cox-2 enzyme) the less negative side effects the nsaid is thought to have because cox2 prostaglandins are what cause pain, edema and fever. Cox-2 specific NSAIDS preserve the functioning of the good cox-1 enzymes that protect the GI mucosa, renal blood flow and platelet function. Many nsaids still block some of the beneficial enzymes but they are becoming more specific.
  • Steroids stop inflammation as well, and intra-articular opioids work within the joint by binding to the opioid receptors found there instead of traveling to the spinal cord to exert their effects. The benefits of intra-articular opioids is thought to last from hours to days without systemic uptake or systemic effects. I have little experience with intra-articular opioids so I am unable to elaborate on this.
  • Moving up the pathway, only two drug classes work at transmission. Local anesthetics and Alpha-2 agonists. Again, the local anesthetics are good here both locally and systemically. As are alpha-2’s like dexmedetomidine. Systemic lidocaine provides great adjunctive analgesia for pancreatitis or other visceral pain. MLK is a combination of drugs that works at three different areas of the pain pathway… Morphine works at transmission and modulation, lidocaine works at transduction and transmission, and ketamine works at modulation and maybe perception.
  • Many many drugs work at modulation including our opioids, nsaids, locals and alpha-2’s. Opioids raise the pain threshold or decrease the perception of pain by acting at the recpetors in the dorsal horn. Opioids are our analgesic drugs of choice because they make pain more tolerable. New to our apothacary are tricyclic antidepressants and nmda agonists. Ketamine has long been known to provide somatic pain relief. We also know that it blocks the effects of glutamate at the NMDA receptor. Stimulation of the NMDA receptor has been theorized to be a key component in sensitizing nociceptive pathways after injury. Alpha-2’s decrease ascending spinal nociceptive transmissions
  • If the signal is able to reach the brain, we can still control it. Generals anesthetic exert their effect here but they don’t reverse the damage done by the noxious stimulus on the way up, that is why it is important to use analgesics as early in the pain pathway as possible. Pre-emptively if possible.
  • There are many benefits to adequate pain control and really no draw backs. Pre-emptive analgesia can decrease the intensity and duration of post-op pain and minimize the likelihood of a chronic pain state. By giving analgesics prior to insult, the spinal cord is not bombarded by impulses that induce changes that can lead to central sensitization.
  • Balanced analgesia is the simultaneous administration of two or more analgesic drug classes or techniques. For example, pre-medding a cat for a declaw with an opioid (like oxymorphone), sedative (such as midazolam) and ketamine, inducing with propofol and maintaining anesthesia with isoflurane then blocking the toes with a mixture of lidocaine and bupivicaine. That seems like a lot of drugs, but my doses are low and my cat is comfortable both intra-and post operatively. And, I’ve attacked the pain signal at each level of the pathway… Transduction and transmission I hit with my local block, modulation with my opioid and ketamine, and perception with propofol and isoflurane. I could even add in an NSAID to give SQ at induction to help with any inflammation. This method is cost effective, keeps patients happy, staff stress free and owner happy because they know that their patients/pets are well taken care of.
  • so, balanced anesthesia is best. Because you are not relying on one drug to do all of the work, you are getting the best out of each analgesic and by using low doses you are decreasing unwanted side effects. A combination of drugs allows you to consider the pain pathway and in doing so you will likely provide adequate analgesia and decrease the chance for developing a chronic pain state which will decrease stress and shorten recovery time. Pre-emptive analgesia is ideal. Why ?
  • The side effects of pain are obnoxious, like this slide, which is of the potential side effects of untreated or under-treated pain. Under-treated pain is almost as bad as untreated pain when it comes to the physiologic changes that can take place within the body. Balanced analgesic techniques, when used pre-emptively, prevents these negative consequences more effectively than when single drug regimes are used .
  • So how do you know if your patient is painful? As we all know, pain can be difficult to assess in many of our patients. Prey animals are very good at looking fine when in fact they are in pain. This type of behavior is innate and evolutionary because a sick animal in the wild is a sure meal. Because of this, it is important to use pre-emptive techniques and pain scoring and to treat animals automatically when you know that the procedure that you will be performing is most likely painful .
  • We often use physiologic parameters to help determine if an animal is in pain. When these increase above what is normal, we have reason to believe that intervention may be necessary. Sometimes an animal’s stress level can elevate these parameters so it is important to look at the big picture. Under anesthesia, these values are essential.
  • A purring cat is not always a happy cat. I worked out in New Glarus and a farmer brought in a cat that had been eviscerated by a hay bailer. She was alive, bright, alert, responsive, and purring. As an interesting aside, Frequencies for therapeutic pain relief are between 50-150 Hz. And Cats purr at frequencies between 20 and 200 Hz. Perhaps cats are the new analgesic???
  • Many of the things that we do can cause some degree of pain, or stress and it is our duty as animal advocates to minimize this as much as possible. Alpha-2’s for nail trims or suture removal can decrease the stress of both patient and staff! Is it always necessary? No, but in some cases it will be.
  • All moderate to severe pain should be adequately addressed. There is no excuse for allowing an animal to experience pain. There is no such thing as pain is good, it keeps him off of his broken leg .
  • The Glasgow Composite Measure pain score or a version thereof is a list of behaviors with a numerical value assigned to it. If the animal is exhibiting a behavior in each category than it gets a number, at the end, the numbers are added up. If the final value is above lets say 15 or above, then pain medication is indicated, if it below 10 or below, then it is not. If it is between 10 and 15 then it is in the gray area. Maybe you’ve gone to the doctor and they’ve asked you what your pain level was on a scale form one to 10, 10 being the worst pain possible… I hate that. It is a similar concept.
  • Pain scoring only works if you use it consistently!


  • 1. The Physiology of Pain Kristen Cooley BA, CVT, VTS (Anesthesia) Globe University Madison, WI
  • 2. What is Pain?
    • sensory and emotional
    • actual or potential
  • 3. What is Pain?
    • Often over looked
    • In 2000 JCAHO
      • mandated pain be 5 th vital sign
    • 2003 AAHA followed suit
  • 4. Noxious stimulus
    • Pain causing
      • Intensity
        • Chemical
        • Mechanical
        • Thermal
  • 5. Nociceptor
    • Pain detecting
      • Found throughout the body
  • 6. Nociception
    • The activity by a noxious stimulus
  • 7. Definitions
    • Allodynia
      • Not typically painful
    • Hyperalgesia
      • Exaggerated response
    • Hyperesthesia
      • Increased sensitivity
  • 8. Types of pain
    • Peripheral pain
      • Visceral
        • Abdominal or thoracic organs
          • Poorly localized
          • Referred
      • Somatic
        • Superficial
          • Skin
        • Deep
          • tendons, joints, muscle, periosteum
            • Easily localized
  • 9. Types of pain
    • Neuropathic pain
      • Damage to peripheral nerves or spinal cord
      • Often difficult to treat appropriately
  • 10. Factors affecting pain
    • Stress
      • Exacerbates pain
        • Environmental changes
        • Physiologic changes
    • Anxiety
      • Exacerbates pain
      • Pain recognition
        • Anxiolytics
        • Too much sedation can mask signs of pain
          • This is inhumane
  • 11. Factors affecting pain
    • Wind-up
      • Sensitize to subsequent stimuli
      • Glutamate
        • Activates NMDA receptor
      • Initiates an intracellular cascade
        • Increases membrane sensitivity to stimuli
    • ‘ Central sensitization’
      • Less tolerant
      • Maladaptive
  • 12. Types of Pain
    • Acute
    • Injury
    • Surgery
    • Inflammation
    • Infection
    • Limits mobility
    • Temporary
    • Chronic
    • Age related disorders
    • Slow to develop
    • May learn to cope
  • 13. Types of Pain
    • Adaptive
    • Normal response
      • Tissue damage
    • Protects from further injury
    • Inflammation is a large component
    • Maladaptive
    • Abnormal response
      • No real purpose
    • Stimulus is gone but pain persists
      • Inappropriately managed adaptive pain
  • 14. The Pain Pathway
    • Transduction
      • Signal formation
        • Chemical signal
          • Inflammatory mediators
        • Electrical activity
          • Recognizable by nervous system
  • 15. The Pain Pathway
    • Transmission
      • How the signal is sent
        • Transmitted through PNS
          • A-delta
            • Fast, small, myelinated
            • Acute pain
          • C-fibers
            • Slow, large, unmyelinated
            • Chronic pain
  • 16. The Pain Pathway
    • Modulation
      • Signal processing
        • Spinal cord
          • Dorsal horn
          • Endogenous systems
  • 17. The Pain Pathway
    • Cross section of the spinal cord
      • Dorsal horn
        • Modulation
    Tissue trauma Signal enters dorsal horn Reflex activity exits ventral horn To higher levels of CNS
  • 18. The Pain Pathway
    • Perception
      • Receiving and interpretation
        • Successful transduction, transmission, & modulation of a painful stimulus
        • Conscious, subjective, and emotional
    Modulation Perception
  • 19. The Pain Pathway & Drugs
    • Transduction (formation)
      • Drugs that work “on site”
        • Local anesthetics
          • Lidocaine, bupivacaine
            • Block sodium channels
  • 20. Transduction & drugs
    • NSAIDS
      • Carprofen, meloxicam, ketoprofen
        • Inhibit the production of prostaglandins from inflamed tissue
  • 21. Arachidonic Acid COX-1 COX-2
    • Prostaglandins for homeostatic
    • functions
      • Integrity of GI mucosa
      • Modulate renal blood flow
      • Regulate platelet function
    • Prostaglandins in
    • inflammation
    • Pain
    • Edema
    • Fever
    Inhibition undesirable Inhibition desirable 5-LOX
    • Leukotrienes
    • GI Ulcers
    • DJD
  • 22. Transduction & drugs
    • Steroids
    • Intra-articular opioids
      • Opioid receptors can be found in inflamed joints
  • 23. The Pain Pathway & Drugs
    • Transmission (sent)
      • Drugs that stop nerve impulses
      • Local anesthetics
        • Locally and systemically (lidocaine only)
          • Preferential tx
          • Great for pancreatitis pain
        • Do not give bupivicaine IV!
    • Alpha-2 agonists
  • 24. The Pain Pathway & Drugs
    • Modulation (processing)
      • Opioids
        • Raise threshold
          • Methadone, morphine…
      • Alpha-2’s
        • Decrease signal
          • Dexmedetomidine
      • Local anesthetics
        • Blocks sodium channels
          • Lidocaine, bupivacaine
      • NSAIDS
        • Carprofen, meloxicam
      • Tricyclic antidepressants
        • Amitriptaline
      • NMDA antagonists
        • Decreases wind-up
          • Ketamine, methadone
  • 25. The Pain Pathway & Drugs
    • Perception
      • General anesthetics
        • Injectables
        • Inhalants
      • Opioids
      • Alpha-2’s
    Z z z z z z z
  • 26. Pre-emptive Analgesia
    • Pain meds given in anticipation of pain
      • intensity and duration
      • Chronic pain state
      • Does not eliminate post-op pain it just makes it easier to control!
  • 27. Balanced Analgesia
    • Simultaneous administration of two or more analgesic drug classes or techniques
      • Synergism
      • Additive
      • Pain pathway
  • 28. Pre-emptive and balanced analgesia
    • Utilizes lower doses
      • Less unwanted side effects
    • More complete analgesia
    • Suppresses the stress response
      • Decreases chronic pain state
    • Shorten recovery
  • 29. Consequences of pain
  • 30. Is pain beneficial?
    • NO!
      • Decrease quality of life
      • Prolongs healing
        • Injury, illness, surgery
    • All tissue injury causes pain
      • Routine or quick procedures
      • Skill of individual
  • 31. Recognition of pain
    • Subjective
      • Know what is normal
        • Species
        • Breed
        • Individual
      • Use common sense
      • Big picture
      • Pre-emptive techniques
      • Remember that it is better to treat pain that isn’t there than to not treat pain that is
  • 32. Recognition of pain
    • Can be difficult to asses
      • Prey species
      • Stoicism is innate and evolutionary
  • 33. Pets in pain
    • Assess:
      • Body posture
      • Appearance
      • Locomotion
      • Behavior
      • Activity level
      • Daily habits
      • Response to people
  • 34. Physiologic signs of pain
    • Increase in monitoring parameters
      • blood pressure
      • heart rate
      • respiratory rate
    • Peripheral vasoconstriction
    • Stress leukogram
      • These signs do not rule pain in or out!
  • 35. Common behavioral responses to pain
    • Pain recognition
      • Whine, whimper
        • Intermittent vocalization
          • Continuous vocalization
      • Arched or abnormal posture
        • Standing with head down, bowing/praying position, hunched
      • Guarding of injured tissue
        • Abdominal splinting/muscle tensing
          • Reaction to palpation of site around injured tissue
            • Snapping/reacting when approaching injured tissue
    Dogs are pack animals, they share emotions with pack members to receive support
  • 36. Behavioral responses to pain
      • Restlessness
        • Frequent position changes
          • Inability to sleep
      • Behavior change
        • Animal becomes timid or aggressive
      • Increased heart rate and blood pressure
      • Hypersalivation
      • Appetite reduction
      • Dilated pupils
      • Altered voiding behavior
  • 37. Behavioral responses to pain
    • Pain recognition
      • Over grooming
        • Growling at nothing
          • Purring
      • Hiding
        • Aggression
      • Squinting
        • Refusal to change body position
      • Guarding injured tissue
        • Skin flicking, muscle tensing
      • Desperate attempts to flee
      • Reduced grooming
      • Appetite reduction
      • Pupil dilation
      • Salivation
      • Restlessness
        • Inability to sleep
          • Sleeping all the time
      • Increased heart rate and blood pressure
    Cats are more solitary animals, they are generally more stoic than dogs; showing pain highlights a cats vulnerability
  • 38. Common procedures & pain
    • No/temporary pain
      • PE
      • Nail trim
      • Suture removal
    • Analgesics typically not necessary
      • Don’t forget about stress!
    • Minor pain
      • Suturing
      • Urinary catheterization
      • IV catheterization
      • Dental cleaning
    • Mild analgesics beneficial
      • Decrease stress of animal and handler
  • 39. Common procedures & pain
    • Moderate pain
      • OHE/castration
      • Declaw
      • Extractions
    • Analgesics are necessary!
      • Butorphanol alone is not adequate for these procedures!
    • Severe pain
      • Fracture repair
      • Cruciate repair
      • Amputation
      • Ear canal ablation
    • Analgesics are essential!
      • Multi-modal is best
  • 40. Pain Scoring
    • Assigns a numerical value to observed behaviors
    • Makes pain assessment more objective
    • Helps puts everybody on the same page
  • 41. Pain Scoring
    • Comfort
    • Movement
    • Appearance
    • Behavior
    • Interaction
    • Vocalization
    • Heart rate
    • Trust your instincts
      • If you feel that an animal is uncomfortable it probably is
      • Pain scores help you to communicate this to the doctor
      • Decreases stress!
  • 42. Questions?