Pain issues and management in veterinary dentistry and oral surgery: Part 2 (Proceedings)
Part II discusses some of the common agents used for managing pain associated with oral surgery in dogs and cats. There are six classes of agents discussed and they are the opiods (opiates), the cox-2 selective NSAID’s, the 5-Lox selective NSAID’s, the alpha-2 agonists, the NMDA receptor antagonists and the serotonin norepinephrine reuptake inhibitors.
The most effective analgesia available for pre, peri and postoperative pain control in dogs and cats is provided by the opiod group. It is important to understand several characteristic of opiods to enable the clinician to make decisions on which agents would best be suited for use in a particular patient. Drugs in this class produce variable clinical effects based upon stimulation of a particular opiod receptor subtype. Selective effects of common opiods on different receptors vary as well. An individual opiate’s ability to bind preferentially to a given receptor is termed receptor affinity. The characteristics of individual opiods determine their effect at a given receptor. (Table 1). These different classes of opiates are listed in decreasing order of receptor affinity: antagonist > partial agonist/mixed agonist antagonist > agonist.
Table 1: Definitions of Opiod Receptor Activity with Examples of Common Agents in Each Class
Pure Mu Agonist = Produces an optimal effect by binding to a given receptor.
Morphine, hydromorphone, fentanyl.
Partial Mu Agonist = Binds to the opiate receptor and produces a less profound effect than a pure agonist. Buprenorphine
Mu Antagonist = Causes no effect at the opiate receptor Naloxone, naltrexone, butorphanol
A full understanding of these concepts aids the clinician in choosing the correct opiate or combination of opiates based upon the species and the degree and duration of the anticipated pain. Opiate receptors are located throughout the body and are concentrated in the central and peripheral nervous system making the agents that bind to them invaluable analgesics.
It is widely understood that mu opiod receptor stimulation results in the most significant analgesic effect beyond that of any other receptor subtype. Research in this field has led to the ability to clone the mu, kappa and delta opiate receptors. Knockout mice that lack specific opiate receptor genes give researchers the ability to study the effects of different opiates on receptor subtypes.
The prototype agent in the opiod category is morphinea . It is the drug of choice for severe acute pain in dogs. Cats have been known to experience more of the undesirable effects at the sigma receptor (Table 1) with administration of morphinea 1 . Studies now suggest that it is likely that the dysphoric effects were due to unusually high doses used in research settings. Evidence now suggests that opiates actually convey euphoric effects in cats when used at lower doses.2.3 In the author’s extensive experience with preoperative morphinea in cats, dysphoria and excitation appear to be an issue mostly postoperatively. In that respect consideration must be given to the combination of agents administered in the preoperative, induction and intraoperative periods combining to exacerbate the expected degree of recovery disillusionment.
Hyperthermia in cats with the use of opiates is predicatble and therefore monitoring is essential.4 Patients should be monitored during the anesthetic periodand up to five hours during post procedure. If hyperthermia becomes significant, reversal agents that are mu antagonists can be administered. Butorphanolb and nalbuphinec are kappa receptor agonists. That property provides some residual analgesia when they are used as mu antagonists to reverse morphine.a Naloxoned is an antagonist at the mu, kappa and gamma receptors so administration of this reversal agent provides no residual analgesia.
Morphinea , in particular will cause vomiting in a significant number of patients. A decrease in incidence occurs with intravenous administration. Histamine release is a problem with rapid administration so morphine given IV must be given slowly over a period of 30 seconds. An alternative to morphinec in cats is hydromorphonee which is an excellent analgesic in this species. Intravenous administration of hydromorphonee in cats provides quicker onset, increased intensity and longer duration with a decreased incidence of vomiting than IM or SQ administration.5 Again hyperthermia is a concern so monitoring temperature is essential.
Oral surgery patients may be painful and difficult to medicate postoperatively per os. Fentanylf transdermal patches are viable options for managing postoperative pain in dogs and cats undergoing oral surgical procedures. The onset of effect in dogs and cats is 18-24 hours and 6-12 hours respectively.6 If using fentanylf patches, the void between placement and onset of action should be adequately covered with additional analgesics.
Butorphanolb is a mu antagonist allowing for only minimal control of somatic pain. It is expensive and frequent dosing is required due to its short half life. Consequently it is a poor choice for managing pain associated with oral surgery.
Buprenorphineg has partial agonist activity at the mu receptor and consequently less profound analgesic properties than would a pure agonist. However it is a safe and effective analgesic and is a great option for use in cats sublingually and transdermally. It is a good choice when anticipating mild to moderate postoperative pain.
Cox-2 Selective NSAIDs
The breakdown of arachidonic acid by cyclooxygenase (Cox) enzymes produces prostaglandins. These proinflammatory compounds are released from various cell types at the site of tissue injury. Other compounds including cytokines and growth factors aid in stimulating the production of additional prostaglandins. Prostaglandins sensitize afferent neurons to noxious chemical, thermal and mechanical stimuli7, 8 and play a major role in the process of maintaining inflammation. Prostaglandins are involved at the site of inflammation and play at significant role at the spinal level.9 Peripheral inflammation upregulates cyclooxygenase enzyme expression in the spinal cord .10 Therefore drugs that can prevent the prostaglandin production can be used to decrease this phenomenon. This may be particularly effective when given preoperatively prior to surgical stimulation.
The non-steroidal anti-inflammatory drugs (NSAIDs) inhibit Cox enzymes. Their use allows for effective treatment of pain and hyperalgesia associated with inflammation.11 Cyclooxygenase-2 (Cox-2) selective NSAIDs have been widely utilized in veterinary medicine as analgesics. Adverse effects consistently experienced with earlier NSAID’s are nowhere near as significant with these newer agents. Adverse effects are still possible however. NSAIDs as sole agents for analgesia can be effective12 however using multiple agents in a multimodal approach offers safety and efficacy beyond that of single agents. An NSAID in combination with an opiate in humans has demonstrated opiod sparing effects in the range of 20-30%.13 At the date of publication no Cox-2 selective NSAID approved for use in veterinary medicine has been show to demonstrate significant advantages over another.