Anxiety appears to contribute directly to the hyperalgesic state through a cholecystokinin-mediated "nocebo" effect.9 That is, pain is to be expected after surgery, but in humans, anxiety and anticipation of pain enhance pain sensitivity.
And in many animal studies, hyperalgesia has been shown to be induced by restraint, novelty, rotation and social defeat10 —all of which occur during a pet's stay in the hospital for surgery. This highlights the important role anxiolytics can play
to mitigate the postoperative pain experience.
From a pharmacological perspective, this refers to phenothiazines such as acepromazine, benzodiazepines such as midazolam
and alpha-2 agonists such as dexmedetomidine. Nonpharmacologically, this can refer to the patient's entire experience, from
the admissions process, to restraint for lab samples and catheter placement, to the environment in which the animal is held.
So the first step in the transoperative pain management process occurs during or shortly after admission: handling the patient
in the most calming manner and place possible and administering anxiolytics as early as feasible during the preoperative timeframe.
The primary mode of action of NSAIDs is to inhibit cyclooxygenase-2 (COX-2), the enzyme that's expressed at the site of inflammation
and results in the production of proinflammatory and vasoactive prostaglandins. Since tissue damage from surgery invariably
leads to inflammatory pain, NSAIDs are clearly indicated. But also, through poorly understood mechanisms (likely by modulating
multiple gene-expression pathways11 ), they appear to inhibit central perception of pain.
Several superior products are now labeled for use in dogs (and some in cats, including the new product robenacoxib), making
them among the most popular pain management medications in veterinary medicine. All seem to be effective, though not all will
be equally effective for every patient.
The main limitation of all NSAIDs revolves around the potential for adverse effects, because both COX-1 and COX-2 enzymes
may be constitutive, that is, consistently present and crucial to the production of cytoprotective prostaglandins (COX-1 in
the gastrointestinal (GI) tract and renal tubules, especially; COX-2 in the renal tubules). Thus, the primary adverse effects
of nonselective NSAIDs may include GI erosion/ulceration and nephrotoxicosis. COX-1–sparing NSAIDs should have a dramatically
diminished GI toxicity profile but will maintain their risk for nephrotoxicosis, especially in low-flow states (COX-2 upregulates
in the renal tubules with local hypotension). Rarely and on an idiosyncratic basis, hepatotoxicosis may occur.
The GI and renal adverse effects can be expected to occur most commonly in higher risk patients, such as those with hypovolemia,
hypotension (including anesthetic procedures, especially those unsupported by intravenous fluids) or preexisting GI or renal
disease; overusage or an inappropriate combination with other NSAIDs or corticosteroids. Notable in this last category is
client administration of aspirin to their pets, which may be unbeknownst to the clinician unless specifically queried in a
thorough history. Unique to aspirin, this NSAID produces a cytoprotective lipoxin through the COX pathway,12 so when COX is inhibited through the use of another concurrently given NSAID, the potential for GI toxicosis is increased
The relative roles and molecular dynamics of COX-1, COX-2 and a possible new variant COX-1b, are still being elucidated. The
final word on the optimal COX-selective or COX-sparing effect to maximize effectiveness and limit toxicity is yet to be heard.
With any use of NSAIDs, the potential for adverse effects needs to be made clear to pet owners (including to withhold the
drug in the event of vomiting or inappetence, usually the first signs of gastropathy), and the avoidance of concurrent NSAIDs
or corticosteroids before and after surgery needs to be a prime point of client education.
Whether to administer NSAIDs preoperatively or postoperatively remains a clinical choice. Evidence of superior efficacy can
be ascribed to dogs when given preoperatively,13 but some clinicians choose to administer in the postoperative period only, out of an abundance of caution to further minimize
the potential for adverse effects. In either event, transoperative intravenous fluids are considered a customary precaution
to take in every anesthetic event.