Practical Pain Management

Elizabeth M. Hardie, DVM, PhD, Dipl.ACVS
Bernie Hansen

 

1.       Do I have to understand complicated neurophysiology to do pain management well?

You don’t have to know complicated brain chemistry, but you do need to understand a few key concepts.  Anatomy governs physiology.  Pain is an experience, and acute pain usually arises from the nervous system response to actual or potential tissue injury, a process called nociception. Anatomy governs physiology, and aPcute pain transmission andusually arises from  perception is basically a three- step pathway.  First, there are the peripheral neuronsrves coming from that connect the painful site to the central nervous system.  The peripheral neurons that give rise to pain may be dedicated solely to signaling tissue injury (nociceptive neurons), or may be neurons that do not normally signal injury unless intensely stimulated. The sensitivity of any of these neurons can be modified with drugs such as nonsteroidal anti-inflammatory drugs and their signal transmission can be blocked with local anesthetics.  Second, there are neurons within the dorsal laminae of each spinal cord segment and brain that transmit the impulse from the synapse with the first-order neurons and integrate the information presented by them, then relay that information rostrally to the cortex of the brain.  The complex processing that occurs during this step may limit or amplify the amount of information that is coded as nociception and passed along to the brain.is transmission pathway is constantly being modified to amplify or dampen the transmission. Centrally acting nNonsteroidal anti-inflammatory drugs, opioids, alpha-2 agonists, and NMDA receptor antagonists act in part by stimulating the natural inhibition of dampening transmission at this level.  Third, the actual conscious perception of nociception and its interpretation as of pain occurs within the cortex of the brain.  This means that the pain perception experience requires consciousness, is associated with emotion and memory, and is highly individual.  Drugs that alter consciousness and anxiety may modify pain perception without modifying nociceptive transmission processing at the first two levels.  If the drugs that alter perception are withdrawn from an injured patient and pain nociception transmission is normal or enhanced, pain may be is perceived as severe.

  The efficacy of acute pain control depends on the level at which you can interfere with its genesisstop transmission.  Ideally, this interference should be directed against nociception at transmission of painful impulses is stopped at the level of the first-order neuron to prevent any stimulation of higher-order nociception..

The second key concept is that of postinjury facilitation. spinal cord wind-up.   Everyone is familiar with the smashed finger that doesn’t hurt much when you first injure it, but that becomes exquisically exquisitely painful several hours later.  This is a phenomenon is due largely to events occurring that happens at both the first and the second levels of transmission.  When The local inflammatory response following tissue injury lowers the there is a barrage of impulses into the spinal cord from the first-order neurons response threshold, recruits quiescent (‘sleeping’) nociceptors, and intensely stimulates non-nociceptive neurons (for example, those associated with touch).  When their output is sufficiently intense, information from the non-nociceptive neurons may be coded as nociception by second-order neurons., transmission is modified.   Consequently, Tthe size of area of the stimulationperipheral field enlarges and the signal intensity presented to , so a given the second order neurons recieves input from more first order neuronsis increased.  Similar changes occur at the second order neurons within the spinal cord, in a process commonly referred to as wind-up. The second order neurons also become more sensitive, meaning that they depolarize in response to progressively less stimulation, and become more likely to code information from those recruited non-nociceptive neurons (e.g., those associated with touch or pressure) as nociception.  These changes give rise to the ‘tenderness’ following injuries, and explain why fire more impulses in response to less stimuli.  Jjust touching the skin next to the an injured area will can result in impulses that are now percieved as pain, rather than touch.

The third key concept is that perception and tolerance of pain transmission and perception are is highly variable.  The experience of Sensitivity to pain varies with many factors such as genetic make-up, with sex, with species and breed, with hormonal influences, with time of day, and with age.  Overall, there is about a 5-fold variation in the need for analgesics among normal individuals with similar injuriesmammals with “normal” nervous systems.  In general:, males require more analgesics than females, anxious individuals need more analgesics than calm individuals, pain is most severe when cortisol levels are low (night for dogs, morning for cats), and immature nervous systems function  areis more deranged and for longer periods after pain injury than mature nervous system functions.

The final concept is that different kinds of pain involve different neurochemistry and may respond best to different kinds of drugs.  Acute pain is simple: the injury happens, it elicits a pain response, and that response fades within 3 days as the injured part stops hurting.  Chronic pain is more difficult, because by definition this pain arises at least in part from abnormal function of the nervous system itself..  Depending on the stimulus (cancer, inflammation, or injury to a nerve), there are differing neurochemical changes that occur within the second-order neurons that can progress to more lasting changes in nervous system structure.  These changes can become permanent,: in that even if the first order nociceptive pain transmission is stopped, second order transmission occurspersists.  Thus, whereas acute pain can be treated with fairly standard methods, with adjustments for the individual variation, s among individuals.  Cchronic pain must be treated early, before permanent changes occur, and may require more sophisticated treatment.

2.       So how do I translate these concepts to actual practice?

Just do it.  Make pain control a priority.  Would you want to go to a dentist or a doctor who hurt you on a regular basis?  You need to be familiar with several classes of drugs: local anesthetics, non-steroidal anti-inflammatory drugs, opioids, alpha-2 agonists,  NMDA receptor antagonists and corticosteroids.  Most of these drugs are already common in veterinary practice: lidocaine, bupivicainebupivacaine, carprofen, morphine, butorphanol, xylazine, medetomidine, ketamine and predinisolone. Some may be may be new to you, such as : buprenorphine, and fentanyl.  You will need to review or learn some anatomy for local anesthetic blocks and epidural injections.  Then apply the concepts: block first order neurons if you can, modify second-order transmission and spinal cord wind-up, relieve anxiety, and if all else fails, modify consciousness.  Treat pain before it occurs, if possible.  If pain is already present, give enough drug to provide relief for THAT patient.  Give pain- relieving drugs long enough (3 days for acute surgical pain). 

Remember that sick patients may be too obtunded by surgery or illness to show visible behavioral signs of pain yet may require the most aggressive analgesic therapy possible.  In addition, consider that animals with systemic inflammation (‘SIRS’) have some sensitization of all peripheral neurons, and may be in considerable distress from injuries that would otherwise be well tolerated (remember how you ached the last time you had a fever?).

Finally, be aware that there are no perfect drugs.  All drugs have side effects and the most effective pain control uses combination therapy.  Many analgesic drugs act synergistically and multi-modal therapy allows use of lower doses that markedly reduce side effects.  Refer chronic pain patients that don’t respond to conventional drugs for complete work-up and tailored therapy.

3.       Acute pain

The most common indications for acute pain control are therapeutic manipulations, surgical operations, dental procedures and trauma.   Rapid therapeutic manipulations may becan be accomplished with distraction therapy.  More prolonged or painful procedures require topical anesthetic cream or gel (EMLA cream, lidocaine jelly) or a local block with lidocaine.  Surgery involving a localized body part (castration, onychectomy, tail docking, ear cropping, biopsy, mass removal, tooth extraction) should be planned with local anesthesia.  UIn dogs, use 2% lidocaine without epinephrine for very short procedures, such as IV catheter placement, and 0.25 – 0.5% or bupivicainebupivacaine with epinephrine, with or without epinephrine, for surgical pain..  Avoid using local anesthetics with epinephrine when infiltrating distal extremities (declaw)In cats, as collateral circulation is limited and ischemia may occur.epinephrine can lead to vasospasm and should be avoided.  If you will be creating pain within 5 minutes of blocking the body part, use lidocaine.  Bupiviacaine provides pain relief for up to 6 hours, but is not effective for 20 minutes.  With both drugs, it is best to use a dose below 2 mg/kg and avoid their use in animals with known heart disease.

Operations involving bones,  major deep tissues, or the thoracic and abdominal body cavities or limbs create pain that cannot be completely blocked with local anesthetics.  Modification of second order transmission thus becomes critical for these patients.  The drugs are administered at the time of pre-medication or induction and then repeated, if needed, during the course of the operation.  The least expensive drug for this purpose is morphine.  Additional options include other opioids (hydromorphone, buprenorphine, fentanyl) or medetomidine.   Nonsteroidal anti-inflammatory drugs that do not markedly alter clotting (carprofen, meloxicam) are also commonly used for this purpose.   Side effects are common with many of these drugs.  Morphine often causes vomiting if administered as a premed, and it is therefore best administered after induction of anesthesia or at the time of anesthetic recovery.  All opioids can cause post-operative ileus or urinary retention.  Butorphanol is expensive, has limited efficacy, and lasts only 1-2 hours in dogs.  Medetomidine causes peripheral vasoconstriction and low heart rate.  Nonsteroidal anti-inflammatory drugs may all reduce renal blood flow and should not be used in  patients with suspected renal compromise.  Patients that have recently received corticosteroids should not be given nonsteroidal anti-inflammatory drugs due to additive GI toxicity.

All patients undergoing major surgery should be protected from the development of spinal cord wind-uppostinjury facilitation.  The NMDA The receptor is intimately associated with that is chiefly responsible for this this phenomenon at the spinal cord is the NMDA receptor.  Two common drugs that block this receptor are ketamine and dextromethorphan.  Low doses of either drug will (0.51-2 mg/kg of ketamine IV or IM, 1-2 mg/kg of dextromethrorphan IM or PO) will significantly inhibit the windup response.  Although even one administration at the time of surgery has been shown to reduce the need for analgesics after surgery in humans, repetition of drug administration for up to 24 hours after surgery will further reduce the need for analgesics. 

A sSpecial mention should be made of the need to limit protect the spinal cord windup during limb major body part amputation.  If the surgeon blocks exposed nerves are blocked with local anesthetic just prior to at the time of transection (a laser cut is better than a sharp scalpel cut is better than an electrosurgical cut) the spinal cord will be protected from a massive barrage of nociceptive input.  In humans, Furthermore, ghost phantom limb pain after surgery is lessened if an epidural (morphine or morphine/bupivicainebupivacaine) is performed.  Finally, careful measures to protect against spinal cord wind-up and to treat pain aggressively for 3 days after amputation will also markedly reduce ghost phantom limb pain sensations.

Epidural analgesia is particularly useful for surgery being performed on body parts caudal to the mid-lumbar regionthorax.  By using a combination of an opioid and a local anesthetic, both first and second order neuron pain transmission can be diminished.  However, in cats, the spinal cord extends further caudally than in the dog.  The “epidural” may in fact be a spinal, as evidenced by cerebrospinal fluid in the hub of the needle.  Opioid alone is used and the dose is reduced.

To avoid prolonged recovery to consciousness Aafter surgery, wait until the animal is extubated to give the first dose of post-operative pain medication, so as to not prolong extubation.  If the recovery is poor, give a sedative in addition to analgesia, rather than more analgesic drug alone.  If an opioid has been used for analgesic, administration of a minute amount of medetomidine (0.25 – 1.0 mcg/kg, 5-10 mcg totalrepeated to titrate the effect) will enhance provide both sedation and analgesia, due to synergistic actions.

The schedule of post-operative pain medication depends on the nursing care available and the level of post-operative pain anticipated.  If the animal is likely to be unattended for 8-12 hours, a nonsteroidal anti-inflammatory drug will provide control of moderate pain.  Drugs which that cannot be used pre-operatively, such as ketoprofen, can be used safely once surgery is completed.  Buprenorphine lasts 6 hours and also provides control of moderately painful conditions.  Hydromorphone or morphine last 3-4 hours and can be titrated to control severe pain.  Alternatively, very low dose medetomidine (1-5 mcg/kg/hour5-10 mcg) can be added to IV fluids for synergistic pain control.  If a fentanyl patch was placed before surgery, no additional therapy may be needed.   If placed applied after surgery, pain should be treated using other drugs until analgesic blood levels of fentanyl are likely to be present (12 hours).  Some animals never absorb fentanyl from a patch, and some absorb subtherapeutic amounts.  Thus, animals treated with a fentanyl patch should be monitored carefully for signs of pain and treated with additional medications.

Most owners are less anxious about taking their animals home after surgery if they have access to oral pain control drugs that can be administered as needed.  For dogs, a nonsteroidal anti-inflammatory drug is usually prescribed.  For more intense pain, a combination of acetaminophen 300 mg/codeine 60 mg is administered.  For cats, either a fentanyl patch is placed or the liquid form of buprenorphine is dispensed for oral administration (0.01-0.03 mg/kg PO q 8-12 hours).  Aspirin may be administered to cats at a dosage of 10 mg/kg q 48 – 72 hours.

Treatment of trauma patients is no different from the treatment of surgery patients, except that the early opportunity to prevent treatment to prevent spinal cord wind-up postinjury facilitation and sensitization of the central nervous system is lostnot possible.  Higher doses of analgesics are therefore needed.  If cardiovascular shock is present, non-steroidal anti-inflammatory drugs are avoided until blood pressure is stable and renal function is normal.  If head trauma is present, and consciousness is altered, treat for the assumed level of pain until assessment is possible.

4.       Chronic pain

                        The most common reasons causes of for chronic pain in animals probably include are degenerative joint disease, vertebral disc disease, and cancer.  Neuropathic pain resulting from lesions within the central or peripheral nervous system is much less common.  Degenerative joint disease is present in 20% of the geriatric population, but many animals will disguise lameness and pain in the veterinarian’s office.  An analgesic trial is always indicated if the owner or veterinarian suspects chronic pain.  If the animal responds to analgesic therapy, it is critical to rule out cancer as a cause of pain.  Once degenerative joint disease is confirmed as the cause of pain, a decision must be made regarding surgical or medical therapy.  If medical therapy is chosen, the owner must be educated that 1) therapy is life-long, 2) weight control is critical to preventing advancement of disease, and  3) controlled daily exercise is critical to maintaining range of motion within the affected joints.  Medical therapy may be multi-modal or single agent therapy.  No one agent works for every patient, but combinations of glucosamine, chondroitin sulphatesulfate, and a nonsteroidal anti-inflammatory agent area nonsteroidal anti-inflammatory agent is usually effective for dogs.  There are no non-steroidal anti-inflammatory agents approved for use in cats, necessitating the use of corticosteroids or oral opioids.  Corticosteroids are reserved for the treatment of animals that have failed other pain control methods, because their use will hasten the progression of degenerative joint disease.

                        Vertebral disc pain is a form of neuropathia produced by direct compression of the segmental nerve root, combined with local meningitis from the extradural inflammation.  It is not related to compression of the spinal cord itself, which instead produces upper motor neuron signs due to reduced function.  Animals with pain only can be treated medically; those with severe loss of spinal cord function may require surgical decompression. unless deep pain sensation is decreased .  Because of their efficacy at reducing nerve root compression from local inflammation, The most effective pain control agents are corticosteroids are effective pain-relieving agents.  They are indicated primarily for cervical disk disease, after ruling out spinal meningitis.  Cage rest and treatment with non-steroidal anti-inflammatory drugs are often effective treatments for thoracolumbar disc pain. Muscle relaxants such as methocarbamol are very useful adjunct analgesics for both cervical and thoracolumbar pain accompanying muscle spasm.  Non-steroidal anti-inflammatory drugs should be used only in dogs that have not been treated with corticosteroids.  Administration , but their use of analgesic drugs is dangerous without complete cage rest and repeated observation for progression of neurologic deficits is dangerous.  Since many owners will not reliably confine their animals, nonsteroidal inflammatory agents are more safely used to treat pain in animals with vertebral disc pain.  Alternatively, oral opioids can be used to treat painful episodes.

            Cancer pain is best treated by removal of the painful part.  If this is not possible, use the World Health Organization pain control ladder: First, treat with nonsteroidal anti-inflammatory drugs.  Then treat with with a combination of non-steroidal anti-inflammatory drugs and weak opioids (codienecodeine, buprenorphine).  Switch to stronger opioids (morphine, fentanyl) when weaker opioids fail.  Add in drugs that potentiate the opioids (oral low dose ketamine, or IV ketamine or medetomidine in a hospice situation).  As the end of life approaches, give opioids in sufficient doses to control pain, even if sedative side effects are present.   Find out which compounding pharmacies in your area work with Hospice, then use these pharmacies when prescribing oral schedule-2 narcotics, since they are familiar with the needed paperwork and monitoring.  It is becoming more common to encounter owners who will refuse to euthanizeatize a terminal patient, making the provision of veterinary hospice a necessity.

            Other causes of Nneuropathic pain is are best assessed and treated by an expert in pain control.  Pain in these circumstances is often associated with cancer invading the nervous system, but other causes include painful neuromas and altered transmission within the spinal cord .cord.   If non-cancerous neuropathic pain is found, treatment with a variety of drugs affecting neurotransmission will be suggested. 

5.       The future

            More and more operations in human surgery are being performed under local analgesia.  The anesthesiologist’s dream drug would be a local anesthetic agent that affects only sensory neurons and lasts 3 days.  Drugs of this sort are being actively searched for.  Central nervous system drugs with more specificity are also in development.  Thus, treatment of acute pain in the future will likely involve combinations of drugs that alter first and second order transmission, with less sedation and alteration of consciousness.  Chronic pain drugs will be more tailored to the cause of pain, as specific neurochemical alterations for various conditions are described.

Table: Analgesic drugs used in dogs and cats

(All drugs are available in the United States.  Not all drugs are approved for use in dogs and cats)

Drug 
Dose for Dogs (mg/kg) 
Dose for Cats(mg/kg)
Lidocaine 2 % solution Up to 7, at site q 1.5-2 hr Up to 2,  at site, q 1.5-2 hr
BupivicaineBupivacaine 0.5 % solution Up to 2, at site q 1.5-24-6 hr. Maximum is 6 mg/kg on day 1, 4 mg/kg/day thereafter Up to 2,  at, at site q 1.5-24-6 hr.  Maximum is 4 mg/kg/day
Bupivaicaine preservative-free 0.25% solution 1ml /5 kg epidural q 4-6 hr Not recommended
Morphine 0.05-1 IV q 1-24 hr 0.02-0.051 IV, q 1-24 hr
0.1-0.5/hour  IV infusion  
0.2-2.0 IM, SQ q 2-4 hr 0.2-0.5 SQ, IM q 3-4 hrs
0.1 epidural q 8 h 0.1 epidural q 8 h
Morphine preservative-free 0.05 spinal q 8 h 0.05 spinal q 8 h
0.5-1.0 PO q 6-8 hr 0.2-0.5 PO q 6-8 hr
Morphine, Sustained Release 1.5-3 PO q 8-12 hr  
Oxymorphone 0.05-0.1 IV,IM, SQ q 2-4 hr 0.05-0.1 IV,IM, SQ q 2-4 hr
Hydromorphone 0.05-0.2 IV, IM, SQ q 2-4 hr 0.02-0.05 IV, IM, SQ q 2-4 hr
Fentanyl, Transdermal 2-5 ugmcg/kg/hr 2-5 ug/kg/hr25 mcg patch
Butorphanol Not recommended 0.2-0.4 IV, IM SQ q 2-4 hr
0.5-1.0 PO q 6-8 hr
Buprenorphine 0.01-0.03 IM, IV, SQ q 6-8 hr 0.01-0.03 IM, IV, SQ q 6-8 hr
0.01-0.03 PO q 6-12 hr
Medetomidine (adjunct) 0.001-0.005 IV, IM 0.001-0.005 IV, IM
Xylazine (adjunct) 0.05-0.1 IV 0.05-0.1 IV
Ketamine (prevent wind-up) 0.51-2  IV bolus, then 1-2 mg/kg/hourq 0.51-2  IV bolus, then 1-2 mg/kg/hourq
Dextromethorphan (prevent wind-up) 1-2  PO  q 6-8 h 1-2  PO q 6-8 h
Carprofen 2 PO q 12 hr 4 PO once
4 PO q 24 hr  
Meloxicam Acute pain:
</= 0.2 PO IV SC once, then </= 0.1 PO qq 24 hr

Long-term therapy:
</= 0.1 q 24 hr

Acute pain:
</= 0.2 PO IV SC once, then <= 0.1 PO q 24 hr for 3-4 days

Long-term therapy:
</=, then  0.1mg/cat q 2448-72 hr

Ketoprofen 1-2 IV, SQ q 24 hrs for 3 days, AFTER SURGERY 1-2 IV, SQ q 24 hr for 3 days, AFTER SURGERY
1 PO q 24 hr for 5 days, AFTER SURGERY 1 PO q 24 hr for 3 days, AFTER SURGERY
Etodolac 105 -15 PO q 24 hr  
Acetaminophen 10-15 PO q 6-8 hrs for 5 days
Long-term therapy:
</= 10 mg/kg q 8 h
Toxic
Acetaminophen 300 mg + Codeine 60 mg

Acute pain:
1-2 mg codeine q 6-8

Toxic
Aspirin 10 PO q 12 hr, NOT NEAR SURGERY 10 PO q 48-72 hr, NOT NEAR SURGERY
Piroxicam 0.3 PO q 24-48 hr Controversial
Naproxen 2  PO q 48 hr Toxic
Polysulphated Polysulfated glycosaminoglycan 5 IM weekly No established dose, dog dose used by some
Glucosamine and chondrioitin sulphatesulfate 13-15 chondroitin sulphatesulfate PO q 24-48 hr 15-20 chondroitin sulphate PO q 24-48 hr
Prednisolone 0.5-1 PO q 12-24 hr, taper to q 48 hr 2 PO q 12-24 hr, taper to q 48 hr