Front Matter

Chapter 19 The Prevention and Management of Pain in Canine Patients 481

Neuropharmacology: the tools
in the toolbox

Nonsteroidal anti‐inflammatory drugs

Nonsteroidal anti‐inflammatory drugs (NSAIDs)
are the most commonly used modalities to man-
age pain, and for good reason: they are highly
effective, commonly available, licensed for use in
dogs, and safe with proper use. Because inflam-
mation is a prime pain‐generating physiological
mechanism, NSAIDs are among the most impor-
tant drugs in the veterinarian’s arsenal.
The primary analgesic action of a traditional
NSAID results from inhibition of cyclooxyge-
nase 2 (COX2), the membrane enzyme that
metabolizes arachadonic acid and results in the
production of pro‐inflammatory and vasoac-
tive prostaglandins, most specifically prosta-
glandin E2 (PGE2). NSAIDs also appear to
inhibit central perception of pain by modulat-
ing multiple gene expression pathways (Wang
et al., 2007). Arachadonic acid is also metabo-
lized by lipooxygenase (LOX) to produce
leukotrienes, which attract polymorphonuclear
neutrophils and promote their adherence to
endothelium. The relative roles and molecular

dynamics of COX and LOX enzyme variants

are still being elucidated, and the optimal LOX‐

and COX‐selective/sparing effect that maxi-

mizes effectiveness and limits toxicity remains

unclear.

All veterinary NSAID products are effective,

although individual patient responses vary.

Their main limitation is the potential for

adverse effects. COX enzymes are crucial to the

production of cytoprotective prostaglandins

(COX1 especially in the gastrointestinal (GI)

tract and renal tubules, and PGE2 through

COX2 in the GI mucosa and renal tubules), so

the primary ADEs of NSAIDs include gas-

troduodenal erosion/ulceration and nephro-

toxicity. Additional concerns include rare

idiosyncratic hepatotoxicity and effects on tis-

sue healing, and with some but not all NSAIDs,

platelet function. There is conflicting evidence

whether NSAID ADEs are dependent on lon-

gevity of use, in addition to the known risk fac-

tors of biological predisposition and (especially)

improper use. The single greatest variable in

preventing NSAID‐related ADEs is the veteri-

narian and veterinary team, who must be aware

of concurrent drug use and patient risk factors,

and ensure proper use, patient monitoring, and

Perception: Perception - Anesthetics(cerebral cortex)

• Opioids


• α2 antagonists


• Benzodiazepines


• Phenothiazines


• NSAIDs
  Modulation (spinal cord)


• Local anesthetic


• Tricyclic antidepressants


• Cholinesterase inhibitors


• NMDA antagonists


• Opioids


• NSAIDs


• α2 antagonists


• Anticonvulsants

Transmission (sensory nerves)

• Local anesthetic


• α2 antagonists
  Transduction (sensory nerve endings, nociceptors)


• Local anesthetics


• Opioids


• NSAIDs


• Corticosteroids

3rd order neuron

Modulation:

dorsal horn of spinal cord

Transmission:

Transduction

1st order neuron

(primary afferent)

Figure 19.2 Multimodal approach to pain management. With multiple modalities each affecting different aspects of
pain processing, the requirements for each drug are reduced while achieving superior effect and minimizing adverse
drug effects. Source: Illustration by Marcia Schlehr.