'Dying is nothing, but pain is a very serious matter.' (Henry Jacob Bigelow, 1871)

What is Pain?

 Humans: an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage.

 The inability to communicate in no way negates the possibility that an individual is experiencing pain.

 Animals: an aversive sensation and feeling associated with actual or potential tissue damage.

Do Animals Feel Pain?

The Bible forbids cruelty to animals in terms of inflicting pain. Descartes said; 'The greatest of all the prejudices we have retained from our infancy is that of believing that the beasts think.' BUT animals react to painful stimuli and experimentally animals choose to self-administer analgesics.

My approach is--'If it hurts us it will hurt them'

Why Treat Pain?

It causes release of catecholamines, pituitary hormone and therefore catabolic state, leading to weight loss and wound breakdown. It leads to glycosemia and insulin resistance, neutrophil leukocytosis, cytokine production (SIRS), poor immune function, poor appetite and an increase in post-op complications.

Pain Pathways--A Simple Approach

 Nociceptors (+inflammatory mediators)

 A fibres (fast) C fibres (slow--dull pain)

 Substantia gelatinosa of dorsal spinal cord

 Modulation, gating (wind up/suppression)

 Spinothalamic and spinoreticular tracts to brain (including cortex) plus local reflex arcs

 Descending control.

 All can be targeted by analgesics

Some Definitions

How to Recognize Animal Pain

Signs include: abnormal posture (hunched, statue-like), abnormal gait, abnormal movement ('restless'), vocalization (or silence), looking/licking painful area, trembling or shaking, depressed response to handling/aggression, sitting alone, anorexia.

Objective Assessment of Pain

Try using the Glasgow Short Form Pain Score for in-patients. Find it at http://www.gla.ac.uk/vet/research/cascience/painandwelfare/cmps.htm. It is very useful in practice and was developed for dogs. In a busy clinic, palpation of the surgical site is the best way to assess post-operative pain.

Despite all this, dogs and cats are still under-analgesed! In a 1999 survey for exploratory laparotomy, 71% of dogs and 56% of cats were given analgesia.

Analgesics

The ideal compound is:

 Easy to administer

 Has reasonable dosing volumes

 Has low dosing frequency

 Is highly effective

 Is safe--no side effects

 Is inexpensive

 Allows good owner compliance

It doesn't exist!

NSAIDs

NSAIDs block cyclo-oxygenase action therefore reduce prostaglandin (PG) synthesis. Considerations:

 PG's are also involved in blood flow regulation--renal and GI systems--side effects

 Good reduction in local inflammation

Use them in young, fit animals, but with care in older or debilitated animals.

Avoid them in renal/hepatic disease, gastrointestinal ulceration, or if steroids already given. There may be potential problems with long term use.

Opioids

They are safe if dosed correctly with minimal side effects! In cats opioids cause marked mydriasis therefore place in a darkened room and approach making a noise! Commonly euphoria may be seen in cats--kneading, purring etc. Vomiting is possible--especially following morphine subcutaneously.

 Morphine: IM, SC or IV (slowly because of histamine release) 0.1-0.2 mg/kg (cats), 0.2-0.5 mg/kg (dogs). Easily titrated to effect. Morphine is given every 4 hours (dogs) and every 6 hours (cats) in UVH, or as required.

 Pethidine: IM or SC only 2-5 mg/kg. It has a short duration of action, requiring re-dosing every 1½-2 hours at least. There may be pain on injection.

 Buprenorphine: Reliable in dogs and excellent in cats. It is a partial mu agonist with very few side effects. Administer SC or IM; or the buccal route is very effective (at least in cats--no controlled dog studies), with 98% bio-availability and faster onset compared with IM route. A dose of 0.02 mg/kg po every 8 hours provides good long-lasting analgesia--can be given at home. It has a slow onset time--up to 45 minutes, but is good for mild to moderate pain.

 Butorphanol: This weak opioid agonist/antagonist is a poor choice as an analgesic, with recent studies showing very limited effect but prolonged sedation.

Local Anesthetics

These are the only true 'an'algesics--prevent wind up and block all afferent pain pathways. Can be given by specific nerve blocks/ring blocks, infiltration, into abdominal / thoracic cavities, wound catheters, brachial plexus for forelimb surgery, epidural for hind limb surgery. Should be applied prior to surgery.

 Lidocaine up to 4 mg/kg--duration 1-2 hours

 Bupivacaine up to 2mg/kg--duration 4-6 hours

 Also EMLA cream (lidocaine and prilocaine)--for skin biopsies, etc.

Alpha 2 Agonists

Avoid xylazine--cardiotoxicity. Medetomidine and atipamezole are licensed. Major cardiovascular side effects occur but these are reversible--use in healthy patients only. They provide good visceral analgesia and are synergistic with ketamine. Use low doses; as low as 2.5 μg/kg. Can spray onto fractious animal mucous membranes!

Ketamine

This is a non-competitive NMDA (N-methyl D-aspartate) antagonist; NMDA receptors in dorsal horn of spinal cord are responsible for 'wind up'. Ketamine when used for general anesthesia provides some post-op analgesia compared to thiopentone and halothane; therefore it acts as pre-emptive analgesic. It is a safe drug for sedation with midazolam in cats. Often is used for general anesthesia with diazepam (dogs) or medetomidine (cats). Infusions of 2-20 μg/kg/min with a syringe pump intra-operatively provides analgesia.

Analgesics--Other Techniques

 Fentanyl transdermal administration: This is a useful technique in dogs where repeat dosing of analgesics is difficult. It may be a useful technique in fractious cats. Patches deliver a set amount of drug; dose: 2-4 μg/kg/hr but takes up to 12 hr to take effect. As yet no controlled studies have been conducted in cats. The patch must be applied to shaved skin and bandaged securely. ?safety of home use?

 Epidural: Lumbosacral space: remember that the spinal cord in cats extends further caudally than dogs, so take care--always check for cerebrospinal fluid and inject half calculated volumes if CSF is seen. Pull hind legs cranially, in sternal or lateral recumbency. Aseptic skin preparation is essential. Dose: 0.1 mg/kg morphine plus 1 mg/kg bupivacaine gives surgical analgesia for 6 hours and analgesia for up to 24 hours. This is a relatively simple technique, but is contraindicated if sepsis, skin infection or pelvic/spinal column trauma is present.

 Tricyclic anti-depressants: e.g., amitriptyline at 0.25-2 mg/kg PO SID. This is used in humans for neuropathic pain. Few side effects occur when used for feline cystitis. There are anecdotal reports of effects for cancer and neuropathic pain management; it is possibly useful as part of multi-modal approach? Can increase the risk of arrhythmias if administered concurrently with anesthetics.

 Gabapentin: Anticonvulsant: uncertain mechanism of action but interacts with the NMDA receptor. Possibly good for neuropathic and bone cancer pain. It is not licensed but suggested doses are 5-35 mg/kg/day divided into 2 or 3 doses (dogs) and 1-4 mg/kg PO SID (cats) as initial level.

 Tramadol: Weak opioid action (analogue of codeine) but devoid of side effects. Acts centrally. Is used for moderate to severe pain. Suggested dose 1-2 mg/kg iv pre-operatively.

 Amantadine: Human anti-viral drug but an NMDA receptor antagonist. Used in cats. Is useful for opioid tolerant cats and synergistic with opioids. Liquid (10mg/ml) formulation. Long duration of action in renal insufficiency. Suggested dose 3-5 mg/kg PO SID.

 Benzodiazepines: Diazepam 2-10 mg/dog PO every 8 hours has been used to alleviate muscle spasm and pain in dogs with spinal injury. It is not analgesic in itself. Repeated benzodiazepine use has been associated with liver toxicity in cats.

Nursing

The role of adequate post-operative nursing is vital--most veterinary patients are comforted by physical contact and reassurance as well as ensuring that physiological functions are adequately maintained.

References

1.  Barnhart MD, Hubbell JAE, Muir WW, Sams RA, Bednarski RN (2002). Pharmacokinetics, Pharmacodynamics and Analgesic Effects of Morphine after Rectal, Intramuscular and Intravenous Administration in Dogs. AJVR 61 (1), 24-2

2.  Booth NH (1988). Veterinary Pharmacology and Therapeutics. Eds N.H. Booth, L.E. MacDonald. Ames, Iowa State University Press

3.  Flecknell P, Waterman-Pearson (Eds) (2000). Pain Management in Animals. WB Saunders, London, UK.

4.  Gaynor JG, Muir WW (2002). Handbook of Veterinary Pain Management. Mosby USA.

5.  Hall LW, Clarke KW, Trim CM. (2001). Veterinary Anaesthesia. W.B. Saunders, London.

6.  Muir W, Hubbell JAE, Skarda RT, Bednarski RM. (2000). Handbook of Veterinary Anaesthesia. Mosby, Missouri.

7.  Peck TE, Hill SA, Williams M. (2004). Pharmacology for Anaesthesia and Intensive Care. Greenwich Medical Media Ltd, London.

8.  Seymour C, Gleed R. (Eds). (1999). BSAVA Manual of Small Animal Anaesthesia and Analgesia. BSAVA, Cheltenham, UK.

9.  Tenant B. (2003). BSAVA Small Animal Formulary 4th Edition. BSAVA, Cheltenham, UK.