pain control

nocioceptors ("noxious" = harmful or undesirable)

when nocioceptors translate noxious stimulus into action potentials

when action potentials (from transduction) are conducted along peripheral (afferent sensory) neurons into the dorsal root of spinal cord.

• unconsious perception of stimulus.  
• when action potential from transduction/transmission enters dorsal horn of spinal cord until it reaches/processed by brain
• OR
• process of transduction, transmission, and modulation of neural signals generated in response to an external noxious stimulus.
• OR 
• physiologic component of pain consisting of processes of neural signals generated in response to noxious stimulus

• CONSCIOUSLY PERCIEVED nocioception
• unpleasant EMOTIONAL and sensory experience associated with actual/potential tissue damage
• causes stress response

• sharp/bright/pricking
• felt in 0.1 seconds post-stimulus, first
• Localized
• mechanical or thermal
• Aδ

• burning/aching/throbbing
• felt 2nd, takes 1 sec or more, increases
• chemical, mechanical, thermal
• hard to pinpoint
• C fibers, nonmyelinated so slower
• tissue destruction

• sensory nerve fibers associated with fast pain, 0.1 sec
• sharp or pricking pain, feel first, LOCALIZE
• A are smallest myelinated
• skin, SQ tissue, periosteum, joints, muscles and viscera

• sensory nerve fibers associated with slow pain, 1 sec, 2nd pain
• dull, aching, throbbing.  Tissue damage and inflammation
• unmyelinated
• skin, SQ tissue, periosteum, joints, muscles and viscera

• nocioceptive pathway, altering or adaptation of nocioception according to circumstances
• peripheral sensory nerve impulses are amplified or dimished in spinal cord
• some direct synapse with projection neurons (sensory info to brain), but some synapse with excitatory or inhibitory before projection.

• Aβ, Aδ and C fibers regulate activity of inhibitory interneurons in dorsal horn
• Aδ, C activation opens gate and inhibits the inhibitory, so stimulates.
• Aβ activates inhibitory to close gate, decrease stim (rub after pain)

• sensory afferent fibers, myelinated
• Aα>Aβ>δ
• skin, muscles, joints
• NON-PAINFUL stimuli (pressure, touch, vibration, mvmt, position)
• stimulation inhibitory to pain/nocio
• large diameter, high velocity

No, CONSCIOUS perception only.  Can feel nocioception.

proprioception, large myelinated fibers

• BALANCE OF INPUT from Aδ/C vs Aα/Aβ
• Aβ can't stop major injury pain, but rubbing a wound after sharp pain can be inhibitory to pain

• activation of sympathetic NS and catecholamine release
• increased secretion of glucocorticoids
• hypermetabolism
• Na and H2O retention
• Activated by pain due to sx or trauma
• self-sustaining neuroendocrine cascade, must be interrupted.  Immunosuppression, catabolism

• nocioception can stimulate autonomic NS (doesn't have to be pain)
• increased tidal volume and resp rate (tachypnea)
• may not be seen due to anesthetic agents

• nocioception can stimulate autonomic NS (doesn't have to be pain)
• increased sympathetic tone, increased cardiac workload
• catecholamine release - increased HR and BP, arrhythmias
• may not be seen due to anesthetics

• catecholamines, cortisol, etc
• hyperglycemia, decreased GI blood flow, reduced wound healing, increased platelet aggregation, decreased cellular immunity.

CHANGES: activity, aggression, appearance, appetite, attitude, facial expression, locomotion, posture, response to handling, vocalization

• acts as a protective mechanism, causing animal to withdraw from stimulus or avoid movement during reparative phase
• Helpful/protective

• exaggerated response that exceeds protective usefulness.  Associated with tissue injury during surgery or trauma.  
• NOT serving protective function

• 2 types (deep and superficial)
• pain originating from periphery
• usually Aδ/fast pain, easier to localize.

• pain originating from skin, SQ tissues or mucous membranes
• usually Aδ/fast pain, easier to localize.

• originating from muscles, tendons, joints or bones
• usually Aδ/fast pain, easier to localize.

• pain originating from abdominal viscera or pleura, thoracic viscera or pleura, internal organs or blood vessels
• usually C fibers, slow pain, hard to localize

pain with predictable duration, usually from injury or surgery

• ongoing, often intermittant pain that persists from months to years.  
• DAMAGING

• pain perceived at uninjured intact tissues a distance away from the presumed causative lesion
• generally produced by deep somatic or visceral injury (vs superficial).  Toothache

• pain arising directly from nerves (nerve damage, injury or dysfunction)
• may be persistent stabbing, shooting or burning
• may be numbness or tingling
• (diabetic neuropathy)

• relief or absence of pain in response to normally-painful stimulus
• includes diminished sensory perception of pain AND alleviation of emotional components

• prevention or minimization of pain prior to patient consciously experiencing (give drugs before pain)
• more effective, decrease dose and frequency
• standard of care, stops from entering CNS

• transient pain in response to a noxious stimulus
• normal protective response, protects body from environment

• pain in response to tissue damage and inflammation
• ongoing leads to maladaptive pain

• chronic adaptive pain leads to physiological changes in brain and spinal cord = chronic pain
• SPINAL WIND-UP PAIN
• retain hyperexcitable state even when stimulus is removed.
• 3 types: neuropathic, central neuropathic, functional

• Stimulation of afferent C-fibers at critical rate causing neurons in dorsal horn of spinal cord to be hypersensitized/over-exciteable
• 2 phases: 1 = hyperalgesia  2= allodynia

neurotransmitter released by C fibers in spinal wind-up pain.  Received by NMDA receptor

• type of glutamate receptor, only open after prolonged depolarization fo post-synaptic membrane at critical rate
• excites post-synaptic neuron

• C fibers in dorsal horn release glutamate and other neurotransmitters
• receptors (NMDA) in ligand-gated ion channels, opens and depolarizes post-synaptic membrane

• phase 1 of spinal wind-up pain
• increased response to stimulus that is normally painful
• less stimulation causes more pain, oversensitivity
• heightened sense of pain at site of tissue damage or in surrounding undamaged tissue

• phase 2 of spinal wind-up pain
• normally non-painful stimuli are felt as painful

• use of more than one drug with different actions to produce optimal analgesia. additive/synergistic effect
• better/longer lasting analgesia than 1 drug alone
• keep reassessing and recalculating

temp, pulse, respiration, PAIN

• depends
• qh for first 6h after sx
• don't wake to assess but do give scheduled meds

• ↑ HR,↑ BP, Δ in RR, lacrimation, salivation, mydriasis, hyperglycemia, elevated serum cortisol levels
• may have other causes, animal may show all or none, or show and have no pain

anxiousness/fear, restlessness, trembling, guarding, lameness, reluctance to move, attempts to escape upon palpation, altered posture, immobalization, aggression, anorexia, lethargy, depression, insomnia, stop caring for self

tension in muscles to prevent palpation

• prayer position
• tensing of muscles esp ventral abdominal muscles as a response to pain

also includes  glazed/worried expression, licking, hiding painful area, agitation, plegia, u/d inside

also includes hiding, crouching at back of cage, purring, squinting eyes, flattened ears, whiskers pulled back/grimace, inappropriate elimination, frenzy, self-mutilation, lack of grooming or over-grooming, hunched posture, not seeking attention, don't want to be handled, head-down position, eye-lids half closed, eyes in slanted position

• head lowering or turning, teeth grinding, nostril flaring, sweating, rigid posture, kicking at abdomen, pawing, rolling, skin twitching, looking at body part, lameness
• stiffly backward ears, orbital tightening, tension above eye, strained chewing muscles, strained muscles, pronounced chin

hunched, lying down, head pressing, teeth grinding, foot stamping, tail flicking, isolation from herd, falling and rolling, expiratory grunting or when ruminating, vocalization (goats)

• simple descriptive scale
• qualitative assessment by observer
• none, mild, moderate, severe, very severe

• numerical rating system
• qualitative assessment by observer
• numerical value assigned to pain description

• Continuous line going from 0 (no pain) to max (100)
• Colorado State

• treat them for pain
• if they resume normal behavior they were

spontaneous pain and hypersensitivity to pain in response to tissue damage and inflammation

transient pain in response to a noxious stimulus

medically induced insensitivity to pain

absense of pain in response to stimuli that would normally be painful

acute anxiety or pain

a state of anxiety or restlessness

spontaneous pain or hypersensitivity to pain in association with nervous system damage or lesion

hypersensitivity to pain resulting from abnormal processing of normal input

pain initiated or caused by primary lesion or dysfunction in the CNS

general term, pain from lesion in PNS or CNS - pain initiated by a PNS or CNS primary lesion or dysfunction

care that relieves or alleviates a problem without dealing with the cause (like hospice)

pain initiated or caused by primary lesion or dysfunction in the PNS

administration of an analgesic before the painful stimulation

central sensitization - heightened sensitivity that results in altered pain thresholds.  Can happen in chronic pain, not just anesthesia.

• produced by severe pain
• dysfunction, disability, systemic inflammatory response (SIRS), distress, suffering, MODS (organ dysfunction), leads to/hastens death

systemic inflammation response syndrome, leads to organ dysfunction

multiple organ dysfunction syndrome, from sickness syndrome and systemic inflammatory response syndrome, death.

• Freedom from thirst, hunger and malnutrition
• Freedom from discomfort
• Freedom from pain, injury and disease
• Freedom to express normal behavior
• Freedom from fear and distress

• suppression or elimination of pain
• suppression or elimination of pain behavior and the promotion of normal behavior
• improve comfort
• return to max function despite residual pain
• removal of stress or distress
• IMPROVE QUALITY OF LIFE

• (where stimulus turns into impulse)
• local block, opioids, NSAIDs

• stop pain at the first-order neuron in the dorsal horn (A-delta, C fibers)
• Local anesthetics, Alpha-2 antagonists

• drugs that stop excitatory neuropeptides which amplify (glutamate, substance P), where body released endogenous opioids to decrease signal
• Local anesthetics, NMDA blockers, alpha-2 antagonists, opioids, SSRI (selective seratonin reuptake inhibitors), TCAs (tricyclic antidepressants)

• chagnes in CNS and PNS associated with nocioception, change in NS response.  Leads to peripheral sensitization and central sensitization.  Peripheral usu from inflammation (chem mediators, reduced threshold), central due to NMDA/increased excitability/reduced threshold.  
• Combination results in increased magnitude and duration of pain

general anesthesia, sedatives, opioids, alpha-2 antagonists

• peripheral, spinal and paraspinal activity. Initial v/d, then constipation.  Feel warm/pant (thalamus), HISTAMINE RESPONSE. Vasodilation. Glucuronidation, bad for cats
• Mu receptor is best analgesia, worst side effects.  Little cardio effect, most respiratory depression, euphoria, bradycardia, addictive.  Schedule II.  
• Delta receptor is a modified mu receptor.  
• Kappa less pain, more sedation.  causes miosis and dysphoria

• best analgesia, most side effects
• bradycardia, hypotension (histamine = vasodilation), sedation, respiratory depression, urinary retention, vomiting (first time only), defection then constipation, panting (thalamus)
• Morphine, oxymorphone, hydromorphone, fentanyl, methadone.  Buprinorphine, torb partial

• protoypical opioid, pure mu agonist
• control II
• no ceiling on analgesia/resp depression
• histamine release (vasodilation) and vomiting
• no cats (glucuronidation to become active)

• 10x more potent pure mu agonist opioid than morphine
• schedule II
• no ceiling on analgesia/resp depression
• no histamine release (vasodilation) and less vomiting/nausea
• Bradycardia common
• no cats (glucuronidation to become active)

• 8x more potent pure mu agonist opioid than morphine
• schedule II
• no ceiling on analgesia/resp depression
• no histamine release (vasodilation) and less vomiting/nausea (but still common)
• increased noise sensitivity
• Bradycardia common
• no cats (glucuronidation to become active), hyperthermia and agitation in cats

• 80-100x more potent than morphine, pure mu agonist opioid
• schedule II
• short-acting so good as CRI (lots of control, less with ketamine): minimal CV depression and hypotension, decreases MAC by up to 63% (less windup, less pain/nocio)
• injectible vs transdermal

• systemic effects with topical application, for post-sx.  Absorption and bioavailability variable, 75-100mg patches the worst so use 2 50's for a larger pet.  Can't cut patch, just use half backing.  
• Put on a flat spot - lumbosacral for dogs, chest/ribs near axillary for cat.  Shave, vacuum, don't scrub (needs oils).  Patch warm to stick best, date/time/inital
• 72h in dogs, 5 days in cats.  Bring in to have removed

Fentanyl liquid, apply like flea/tick.  last 72h, released under risk-management.  Keep kids/adults away from pet for 72h.

• pure mu agonist opioid, delta agonist and NMDA antagonist, so helps with spinal windup, prevents opioid tolerance
• least likely to cause vomiting
• bradycardia and respiratory depression at high doses
• synergistic with ace (prevents brady and resp. depression)

• partial mu agonist, VERY HIGH AFFINITY, can't get back off (antagonist for other mu drugs, possibly kappa antagonist).  May antagonize endogenous opioids, decreases sedation
• few adverse effects, analgesic ceiling, delayed onset (30-60min)
• Simbadol SQ for cats, otherwise IV, IM, transmucosal

• weak mu antagonist, kappa agonist.  NOT FOR PAIN, may reverse some pure mu.  Causes release of GABA due to kappa, some minor short-lived visceral analgesia (D 30m-1h, C 1-3h), sedation.  No resp depression  
• in Kitty Magic

• butorphanol, dexmedetomidine, ketamine
• ket vs dex to keep HR steady
• watch for vomiting in cats due to dex

butorphanol, dexmedetomidine, midazolam

• kappa agonist, partial mu antagonist
• not controlled
• very little pain control (mild and short) (non-controlled torb)
• visceral rather than somatic pain
• minimal sedation, resp depression or cardio effects
• best when combined with alpha-2 agonist

• mu receptor antagonist, reversal for opioids (but not total buprenorphine), short duration so may have to dose again.  Torb not reversed very well
• not controlled

• mu receptor agonist (minimal in dogs, good in cats but bitter), serotonin and norepinephrine reuptake inhibitor
• DON'T combine with SSRI or MAO inhibitor, causes serotonin syndrome (watch with prozac, destabilizes autonomic NS)
• commonly sedation, occasional restlessness, some GI upset.  Oral.

alpha-2 agonists

• analgesia and profound sedation, biphasic CV (pre-synaptic = vasoconstriction/hypertension/bradicardia, then post = block Ca/norepi, vasodilation, hypotension WITHOUT TACHYCARDIA, atropine doesn't help).  Decrease O2 delivery.  V in cats, respiratory depression and increased urine production 
• CRI, synergistic with opioids, good for opioid dysphoria
• reversed with atipamezole
• xylazine, medetomidine, dexmededomidine

• Reversible sedation in healthy pets
• periop IV bolus or CRI (reduce MAC, synergistic with opiods, post-op sedation and analgesia (short))
• IM with ketamine and opioid for short procedures (magic)
• decrease opioid in dysphoric pets
• NOT BOX DOSE

• Alpha-2 antagonist
• reversal agent, given IM.  Best if given in thigh muscle, less fat so absorbs faster

"good" prostaglandins, COX1, physiologic functions like GI mucus health, possibly platelet function inhibition.

COX2, inflammatory.  Some still important for physiologic function, like normal nerve transmission, support of renal perfusion by causing renal vasodilation in low-flow states so NO NSAIDS IN HYPOVOLEMIA OR HYPOTENSION

• inhibit cyclooxygenase pathway of arachadonic acid metabolism to block prostaglandin production. COX 2 selective option, still some COX1 inhibition. Reduce inflammation and peripheral nocioceptor sensitization. Minimize intra-op bleeding.
• side effects are mechanism-based (GI ulcers, renal toxicity) or idiosyncratic (hepatotoxicity with carprofin).  GI ulcerations and hemorrhage most common

• glucuronidation so careful in cats (meloxicam or onsior only).
• avoid hypovolemic, hypotensive or renal/hepatic/GI dz

• feline-specific 3-day targeted Cox-2 NSAID for cats 
• causes hepatotoxicity in dogs

• sodium channel blockers, so COMPLETE ANESTHESIA, stops transduction, transmission, modulation, etc. decreased dorsal horn = decreased wind-up.  Can produce mild sedation to decrease MAC and other drugs
• Can be local (line block over incision) or regional (dental block, over an area)

• local tissue swelling, bleeding, inflammation
• CNS (muscle tremors, seizures, coma)
• CV collapse
• decreases EVERYTHING that requires depolarization
• NO bupivicaine IV, causes CV collapse.  ONLY LIDOCAINE IV, ONLY IN DOGS.

kills escape beats so no cardiac output

• lidocaine (rapid onset, short duration, stings)
• bupivicaine (later onset, longer duration)
• increased volume helps, add sterile water.  Can add low-dose opioids (bup or morphine) to increase duration to 20h

• "soaker catheter" locoregional block.  
• catheter with holes, sewn into deep wound, CRI for 48-96h.  Extends duration of local.

• infraorbital foramen block, 107/207 forward
• mandibular block, inside back of jaw, whole mandible
• mental foramen block, 305/306 forward

• three point locoregional block for onchyectomy
• medial to accessory carpal pad
• lateral and proximal to accessory carpal pad
• dorsal medial carpus

• locoregional block for surgeries affecting caudal aspect of P.  Usually opioid (don't block motor so legs can be used) but can include local (minor motor block).  
• Inject into lumbosacral or sacrococcygeal (blocked cats) space, between dura and ligamentum flavum.  
• Too far will go intra-thecal and will migrate higher, into C5-C6 and paralyze diaphragm
• 24h analgesia with little/no side effects.  Get CSF, subdural, TOO FAR

placing drug around nerve to be absorbed

pain mgmt for limb surgeries, use peripheral nerve locator and inject perineural

• multimodal to minimize risk and maximize safety and comfort.  
• Keep calm to minimize stress/anxiety/sympathetic tone/catecholamine release
• minimize pain by stopping before starts, hit from many directions
• chemical anesthesia to reduce MAC where possible

precisely calculated drug delivered continuously.  Start with loading dose or CRI takes 3-5 half-lives, then steady state.

• Good for CRI in dogs, analgesic and sedative.  Can prevent ileus
• glucuronidation in cats, NEVER IV
• rapid onset, short duration, stings

• dissociative anesthetic and NMDA antagonist, prevents wind-up
• improves opioid sensitivity, reduces tolerance, minimizes hyperalgesia
• good for CRI

• oral mu opioid, oral for humans and cats.  Also inhibits serotonin and norepinephrine uptake to increase inhibition of neurons.  Only the last pertains to dogs.
• BITTER LIKE METRO
• short half-life
• not with SSRIs MAO inhibitors, TCAs (no fluoxitine), leads to seratonin syndrome

flu drug with NMDA antagonist abilities.  Combines with NSAIDs, causes diarrhea but short-lived.

oral anticonvulsant, not sure how it works, LIKE gaba (inhibitory neurotransmitter). Neuropathic and chronic pain. Causes sedation

• tri-cyclic anti-depressant. Increases inhibition of pain signal
• neuropathic pain in humans, good for chronic feline interstitial cystitis in cats
• not with SSRI or MAO inhibitors

• injectable polysulfated glycosaminoglycan (PSGAG) for pain managment for joint disease or injury
• only supplement approved by the FDA. Anti-inflammatory that inhibits degradory enzymes and stimulates chondrocytes. From hyaluronic acid (gives synovial fluid its viscosity), restores viscosity to retain nutrition and health of cartilage, reduces prostaglandins (anti-inflammatory) and reduces free-radicals from joint degredation.  IM, no adverse effects, possible platelet inhibition

• prevents stiffness and muscle atrophy
• movement causes cartilage to be bathed in synovial fluid, gives it nutrition, very important

support the limb

replace the limb

• moving of a joint through its range of motion without exertion by the patient
• returns to normal range of motion
• stimulates cartilage regeneration and increase nutrition
• prevent loss of motion in neuro disorders
• Should hurt

• removes heat when applied to the body
• causes vasoconstriction to reduce postop bleeding and bruising
• slows nerve conduction to decrease pain
• decreased enzyme activity reduces inflammation
• cryo for first 72h, then alternate.  10-15m, not over metal or directly on skin

• low energy laser for accelerated cell division, increased WBC phagocytosis, stimulation of fibroblasts and collagen formation, mast cell degranulation (vasodilation)
• Caution, retinal damage (bouncing too), not over metal implants or cancer

• increases blood flow and lymphatic drainage
• never pain, calm and quiet, different techniques to stretch and decrease potential for injury

resistance through entire range of motion to build strength, improve lung capacity, increase blood flow, reduce concussive force on joints, and adjust heat and depth as necessary

needles over neurovascular bundles, constant noxious stimulus, gate closes.  Increases blood flow to area, some endogenous opioids, enkephalins and serotonin release

small nerve bundles near major blood vessels