The physiology of pain (Proceedings)

What is pain?

• Pain is a complex sensory and emotional experience that can be associated with actual or potential tissue damage. Despite its importance, it is often overlooked. It wasn't until the year 2000 that it was recognized as the 5th vital sign in human medicine along side temperature, pulse, respiration and blood pressure. In 2003, AAHA made the assessment of pain the 4th vital sign (temp, pulse, resp, pain = TPRP)

Definitions

• Nociception

o Nervous system activity produced by a noxious stimulus

• Noxious stimulus

o A stimulus capable of producing pain; can be chemical, mechanical or thermal

• Nociceptor

o A receptor that detects painful stimuli, they are found throughout the body

• Can detect either one type of noxious stimuli, or all three

• Allodynia

o Pain produced by a stimulus that is not typically painful

• Hyperalgesia

o An increased or exaggerated response to a painful stimulus at he site of injury or nearby

• Hyperesthesia

o Increased sensitivity to stimuli that is not considered painful

• Peripheral pain

o Visceral (abdominal or thoracic organs); poorly localized, may be referred and seem cutaneous in origin

o Somatic (superficial- skin; deep- tendons, joints, muscle, periosteum); easily localized

• Neuropathic pain

o Pain resulting in damage to peripheral nerves or spinal cord. Often difficult to treat.

Factors affecting pain

• Stress

o Can exacerbate pain through nervous system modifications in response to tension.

o Can result from pain or external stressors like environment or internal like disease

• Anxiety

o Can also exacerbate pain and make it difficult to recognize

o Low dose anxiolytics may be used in combination with analgesic when pain is suspected

• High doses of a sedative/tranquilizer may mask pain without alleviating it, this is inhumane.

• Wind-up

o Noxious stimuli can sensitize the nervous systems response to subsequent stimuli

o Patients who experience unrelenting pain release an increased amount of a neurotransmitter called glutamate. This increase activates the NMDA receptor (normally inactive) which then activates an intracellular cascade that increases the membranes sensitivity to subsequent stimuli. This "central sensitization" can last for hours to days or even longer.

The pain pathway

• Transduction

o A painful stimulus becomes a chemical signal (release of inflammatory mediators secondary to cellular injury) that is translated into electrical activity at the sight of injury

o That energy is converted into a signal that the nervous system can understand

• Transmission

o Pain signal is transmitted through the peripheral nervous system to the spinal cord via nerve fibers

• A-delta (small, myelinated, fast; acute pain)

• C-fibers (large, unmyelinated, slow; chronic pain)

• Modulation

o Pain signal enters the spinal cord at the level of the dorsal horn and is modified by endogenous systems and is then sent to higher levels of CNS utilizing neurotransmitters (exactly what happens here is still up for debate)

o Opioids work at modulation (as do our endogenous opioids) to decrease the intensity of the pain signal that is sent to the brain

• Perception

o Successful transduction, transmission and modulation of a painful stimulus

o Conscious, subjective and emotional

The Pain Pathway and Drugs

• Transduction

o Drugs that work "on site"

o Local anesthetics like lidocaine and bupivacaine

• Block sodium channels necessary for nerve impulse transmission

o NSAIDS

• Inhibit production of prostaglandins from inflamed tissue (decreases the release of the chemical signals)

• Best when used pre-emptively

o Steroids

o Intra-articular opioids

• Opioid receptors can be found in inflamed joints

• Transmission

o Drugs that stop nerve impulses like lidocaine and bupivacaine (locally only)

• Work both locally and systemically

• Lidocaine CRI 25-50 µg/kg/min (works systemically because licocaine will preferentially go to nerves that are firing more)

• Great for pancreatitis or other visceral pain

• Do not use bupivacaine IV

o Alpha-2 agonists

• Modulation

o Opioids

• Raise the pain threshold, make pain more tolerable

o NSAIDS

o Alpha-2 agonists

• Decrease pain signal from spinal cord to brain

o Local anesthetics

• Blocks sodium channels

o Tricyclic antidepressants

o NMDA antagonists

• Ketamine, methadone (also and opioid)

• Perception

o General anesthetics

• Barbiturates, non-barbiturates (propofol), inhalants

o Opioids

o Alpha-2 agonists

Pre-emptive analgesia

• Pain medications given in anticipation of pain (pre-meds)

o Decreases intensity and duration of post-op pain

o Minimizes the likelihood of a chronic pain state

o Does not eliminate post-op pain, just makes it easier to control

Balanced analgesia

• Simultaneous administration of two or more analgesic drug classes or techniques

o Many drugs have additive or synergistic effects when given together

o Inhibition of nociception can be achieved along different points of the pain pathway

Benefits of pre-emptive and balanced analgesia

• Utilizes lower doses

• Less unwanted side effects

• More complete analgesia

• Decrease incidence of chronic pain state

• Suppresses the stress response to pain and injury

• Shorter recovery through improved tissue healing

Recognition of pain

• Can be difficult to assess, especially in prey species (rabbits, horses...)

o Innate, evolutionary

o A sick or injured animal is vulnerable in the wild

• Pain is subjective

o Know what is normal for different species, breeds, individuals

o Observe behavior pre-operatively

o Use common sense (was a painful procedure performed?)

o Evaluate the whole picture (what was done, what was given, what doses...)

o Use pre-emptive techniques and balanced analgesia

o It is better to treat pain that isn't there than to not treat pain that is

Physiologic signs of pain

• Increase in parameters (due to an increase in circulating catecholamines)

o Heart rate, respiratory rate (including change in pattern), blood pressure

• Peripheral vasoconstriction

Common behavioral responses to pain

• Signs are unique for each species as well as for each individual. Use both interactive and non-interactive ways of assessing comfort levels. The assessment of pain is subjective so be sure to gather as much info as possible if you need to convince someone that animal is uncomfortable. Sometimes you may be incorrect, but it is better to treat than to leave an animal in pain (remember, stoicism is a survival technique).

• Dogs (Pack animals, share emotions with pack to receive support, easier to evaluate pain)

o Whine, whimper (anesthesia recovery and opioid administration may also cause this, evaluate in conjunction with other parameters)

o Intermittent vocalization (like when changing position)

o Continuous vocalization (can also indicate dysphoria)

o Timid or aggressive (outgoing dogs may become timid, or nice dogs may become aggressive in response to pain- this can be either acute pain or chronic)

o Fixed stare with arched posture, or restlessness (opioid administration can also cause restlessness- try giving with low dose sedative with opioid for neurolept analgesia)

o Guarding of injured tissue (abdominal splinting/muscle tensing, reaction to palpation of injured tissue, snapping when approaching injured tissue, reacting before being touched)

o Appetite reduction

o Altered voiding behavior

o Rolling, thrashing (may also be seen with emergence delirium)

o Dilated pupils (may also be seen with opioids and ketamine)

o Hypersalivation (may also be seen with opioids but subsides rather quickly)

o Increase heart rate relative to baseline

o Abnormal posture (standing with head down, bowing, hunched, praying position)

o Restlessness

o Unable to sleep (may sleep for only a few minutes at a time)

o Frequent position changes

• Cats (more solitary animals, more stoic than dogs, showing pain highlights vulnerability, difficult to assess pain in cats)

o Groom, growl, purr (over grooming, growling at nothing, important to remember that purring does not indicate a happy cat in all situations)

o Hide or become aggressive (trying to be invisible or lashing out)

o Squint, refusal to move or change body position (very common pain sign in cats- statue cat)

o Guarding injured tissue (skin flicking, growling when near, tensing muscles)

o Appetite reduction or anorexia

o Reduced grooming (unkempt appearance is common ± bald spots near pain site- chronic)

o Altered voiding behavior (refusal to abide by litter box law)

o Pupil dilation (some drugs will also do this)

o Incessant licking

o Desperate attempts to flee

o Salivation (cats often salivate when given oral medications)

o Increased heart rate relative to baseline

o Restlessness

o Inability to sleep

Pain scoring and YOU

• A monitoring sheet that assigns a numerical value to observed behaviors

• Makes pain assessment more objective

• Helps put everybody on the same page

• Assess a variety of things from both near and far...

o Heart rate and respiratory rate and character

o Comfort level, movement, appearance

o Behavior, vocalization, interaction

• Trust your instincts

o If you feel that an animal is uncomfortable, it very well may be

o Stay calm and push your emotions aside (be analytical)

• Pain scores help you communicate with doctors and other team members

• Decreases technician stress!

• Pain scoring works best when used consistently

References

Hellyer PW, Robertson SA. Pain and its management. In: Tranquilli WJ, Thurmon JC, Grimm KA, eds. Lumb & Jones Veterinary Anesthesia and Analgesia. Iowa: Blackwell, 2007

Tranquilli WJ, Grimm KA, Lamont LA. Pain Management for the Small Animal Practitioner. Wyoming:2004.