Introduction

Understanding and treating pain in animals is one of the most challenging tasks in veterinary medicine. In the last decade there has been a growing interest in research aiming to understand the mechanisms underlying animal pain, its diagnosis and methods to improve the therapeutic options. One of the most common obstacles concerning pain therapeutics is the treatment of refractory patients to conventional therapies. Effective pain relief requires some basic understanding of pain itself. It is important to understand that there are different types of pain that a patients can experience, necessitating different approaches to therapy. The purpose of this lecture is to describe the mechanisms of pain as well as a systematic approach to "refractory" patients management, including the practical aspects of pain assessment and the use of new drugs and dosage regimens.

Analgesics for Chronic Pain in Dogs

 Paracetamol (acetaminophen)

 10–15 mg/kg PO q 8 hr for 5 days.

 Long-term therapy: up to 10 mg/kg every 12 hours.

 Seems to be associated with less gastrointestinal side effects than regular NSAIDs, and not been noted to be associated with renal toxicity.

 Can be combined with regular NSAIDs (e.g., meloxicam or carprofen) in severe cancer pain.

 Paracetamol (acetaminophen 300 mg) and codeine (30 or 60 mg)

 Dose on 10–15 mg/kg of acetaminophen.

 Above doses that correspond to 2 mg/kg of codeine, sedation can be seen as a side effect.

 Amantadine

 1.0–4.0 mg/kg PO q 24 hrs.

 This drug is an NMDA antagonist (although originally marketed as an antiviral agent) and seems to produce significant level of analgesia when given in combination with a NSAID.

 Loose stools and excess GI gas can be seen at higher doses for a few days.

 Amitriptyline

 0.5–2.0 mg/kg PO q 24 hrs.

 This drug augments the descending serotonergic system that is one of the body's endogenous analgesic mechanisms.

 It is not a 'strong' analgesic, but, like amantadine and tramadol and codeine, is useful when combined with a NSAID or paracetamol.

 Codeine

 0.5–2.0 mg/kg PO q 24 hrs.

 Sedation can be seen at the higher doses.

 Carprofen

 2 mg/kg PO q 12 hrs; 4 mg/kg PO q 24 hrs.

 Is a COX-1 sparing NSAID and a moderate preferential COX-2 inhibitor.

 Deracoxib

 3–4 mg/kg PO q 24 hrs for 7 days, then 1–2 mg/kg PO q 24 hrs long-term.

 Specific COX-2 inhibitor approved for use in dogs.

 As a very specific COX-2 inhibitor, laboratory evidence suggests it should not be used in animals with existing gastrointestinal ulcers as it may inhibit healing.

 No safer in renal compromise.

 Fentanyl, transdermal

 2–5 mcg/kg/hr

 Can be very useful in the short-term control of cancer pain. For long-term therapy, usefulness is limited due need to change the patch every 4 to 5 days, and the expense thus involved.

 Firocoxib

 5 mg/kg PO q 24 hrs.

 Specific COX-2 inhibitor approved for use in dogs.

 No safer in renal compromise.

 Gabapentin

 3–10 mg/kg PO q 24 hrs.

 The best effects are seen when used in combination with other analgesics such as NSAIDs or paracetamol (acetaminophen).

 Glucosamine and chondroitin sulfate

 13–15 mg/kg chondroitin sulfate PO q 24 hrs.

 Can be used in a variety of cancer pains due to its mild antiinflammatory and analgesic effects. Best used in combination with a NSAID or other analgesic.

 Meloxicam

 0.2 mg/kg PO day 1, then 0.1 mg/kg q 24 hr

 Is a preferential COX-2 inhibitor.

 Morphine, liquid

 0.2–0.5 mg/kg PO q 6–8 hrs.

 Can be useful for dosing smaller dogs where the morphine tablets are not suitable.

 Sedation and (particularly) constipation are side effects that are seen as the dose is increased.

 Morphine, sustained release

 0.5–3.0 mg/kg PO q 8–12 hrs.

 Doses higher than 0.5–1.0 mg/kg are often associated with unacceptable constipation according to owners, so suggest using 0.5 mg/kg several times a day.

 Pamidronate (one of the bisphosphonate class of drugs)

 1–1.5 mg/kg slowly intravenously, probably once a month (although this has not been defined yet).

 This drug inhibits osteoclast activity, and thus only provides analgesia in cases suffering from a primary or metastatic bone tumour that is causing osteolysis.

 Piroxicam

 0.3 mg/kg PO q 48 hrs.

 Despite its widespread use as a mild 'chemotherapeutic agent' for epithelial tumours, the incidence of side effects in dogs is not known.

 Prednisolone

 0.25–1 mg/kg PO q 12–24 hrs; taper to q 48 hrs. if possible after 14 days.

 Do not use concurrently with NSAIDs. Can be particularly useful in providing analgesia when there is a significant inflammatory component associated with the tumour.

 Tepoxalin

 10–20 mg/kg PO on day 1, followed by 10 mg/kg daily.

 This NSAID is a 'dual inhibitor,' that is, it inhibits both cyclooxygenase and lipoxygenase enzymes.

 It is likely to be particularly useful in cancer pain where there is a significant inflammatory component.

 Tramadol

 4–6 mg/kg PO q 8–12 hrs.

Analgesics for Chronic Pain in Cats

 Amantadine

 3.0 mg/kg PO q 24 hr

 This drug has not been evaluated for toxicity but is well tolerated in dogs and humans, with occasional side effects of agitation and GI irritation.

 May be a useful addition to NSAIDs in the treatment of chronic cancer pain conditions.

 The 100-mg capsules need to be re-compounded for cats.

 Buprenorphine

 0.02 mg/kg sublingual q 6–7 hrs.

 Feedback from owners indicates that after 2–3 days dosing at this dose, anorexia develops.

 Smaller doses (5–10 mcg/kg) may be more appropriate for "long-term" administration, especially in combination with other drugs.

 Flunixin meglumine

 1 mg/kg PO single dose.

 Glucosamine/Chondroitin sulphate combinations

 15 mg/kg chondroitin sulphate PO q 12 to 24 hrs.

 This combination appears to produce mild antiinflammatory and analgesic effects in cats more predictably than in dogs. Can be used in conjunction with NSAIDs, opioids and amantadine.

 Meloxicam

 0.2 mg/kg PO on day 1, followed by 0.1 mg/kg PO daily for 4 days, then 0.05 mg/kg daily for 10 days, then 0.025 mg/kg daily.

 This drug is particularly well received by cats due to its formulation as a honey syrup. Also, the drop formulation makes it very easy to gradually and accurately decrease the dose.

 Morphine (oral liquid)

 0.2–0.5 mg/kg PO TID–QID.

 Best compounded into palatable flavoured syrup; however, cats usually strongly resent this medication. Morphine may not be as effective in cats as it is in dogs.

 Prednisolone

 0.25–0.5 mg/kg PO q 24 hrs.

 Can be particularly effective in cancers associated with significant inflammation (such as squamous cell carcinoma of the oral cavity in cats). Not to be combined with concurrent NSAID administration.

 Tramadol

 4 mg/kg twice daily.

 Transdermal fentanyl patch

 2–5 µg/kg/hrs.

 A 25-µg/hr patch can be applied to an "average" cat (3.5–5.0 kg). In smaller cats, other methods of providing analgesia should be sought as it is not recommended to cut patches in half and covering half of the patch gives unpredictable results. The decay in plasma levels following patch removal is slow.

Adapted from: Lascelles D. Relief of chronic pain in cats and dogs: multimodal drug therapy. In: Otero P, ed. Dolor. Evaluación y Tratamiento en Pequeños Animales. Buenos Aires, Argentina: Editorial Intermedica; 2004.