The framework of effective pain management systems rests solidly on the foundation of recognition/assessment, pre-emption,
and using multiple modalities. Multiple modalities allow for intervention at several different places of the nociceptive
pathway, increasing effectiveness and minimizing the need for high or protracted doses of any one particular drug. It is
well-established in human medicine, for example, that the use of adjunct medications will minimize the use of PCA (patient-controlled
analgesia) opioids with a resultant decreased incidence of adverse effects such as nausea and constipation.
Chronic pain is not merely acute pain of extended duration. Rather, it is a maladaptive state whereby the discomfort transcends
the original injury or stimulus, and becomes instead an innate feature of the central nervous system. Normal nociception
is replaced by a constellation of microanatomic, physiologic, and molecular changes both centrally and peripherally, which
result in an increased sensitivity to both noxious and non-noxious stimuli.
A phencyclidine dissociative anesthetic, the evidence is building for its pre-emptive and preventive effects when given at
subanesthetic doses in an intravenous constant rate infusion. Ketamine binds to a phencyclidine receptor inside the NMDA
receptor, i.e. the calcium channel would already have to be open and active for ketamine to exert its effect. However, once
bound, it decreases the channel's opening time and frequency, thus reducing Ca+ ion influx and dampening secondary intracellular
signaling cascades. Hence it is unlikely (and has not been shown) to be truly analgesic in nature. Rather, it appears to
be protective against hyperalgesia and central hypersensitization in the post-operative setting, including in the dog.
Local anesthetics were once a mainstay of pain management in veterinary medicine, and may now be one of the most under-utilized
modalities. They exert their action by binding to a hydrophilic site within sodium channels, thereby blocking it and disallowing
the Na+ influx; thus neurons may not depolarize and thus the effect can be complete anesthesia to a site rather than mere
analgesia. Various local anesthetics will have variable onsets and duration of action, and they may be combined for a rapid
and extended effect. The locality of administration is often limited only by the clinician's ability to learn various utilities
and anatomic landmarks; few are outside the scope of any clinician to master. They include, but are not limited to local
line or paraincisional blocks, regional blocks such as carpal ring, dental nerve, and intercostal blocks, subcutaneous diffusion
blocks, testicular blocks, intra-articular blocks, epidurals, transdermals (EMLA, Lidoderm). Lidocaine administered intravenously
has been shown in humans to speed the return of bowel function, decreases postoperative pain, minimize opioid consumption,
and shorten the hospital stay after abdominal surgery; Systemic, intravenous infusion of lidocaine has also been shown to
elicit a sustained effect on neuropathic pain in humans, and may have a specific point of action in the brain.
Gabapentin is labeled for use as an anti-convulsant drug but is in widespread human use for its analgesic properties. While
structurally similar to GABA, it is not a direct agonist, although it may have indirect effects on GABA metabolism such as
increasing intracellular stores. Another leading hypothesis is that it exerts effect through interaction with the alpha-2-delta
subunit of the voltage gated calcium channel. In a study of women undergoing hysterectomy, only the patients receiving both
NSAID and gabapentin were completely satisfied with their post-operative pain management, when compared to women receiving
either NSAID or gabapentin alone, and in a meta-analysis of 896 patients undergoing a variety of surgical procedures, gabapentin
significantly reduced pain at both 4 and 24 hours post-op when compared to placebo. Pharmacokinetic studies in dogs reveal
that it may have a half-life of 3-4 hours in the dog, suggesting a TID administration schedule. The primary adverse effect
in dogs appears to be somnolescence (as in humans) which usually will spontaneously resolve over a few days acclimation time.
Gabapentin has become a popular in human medicine since its introduction in 1994 for many chronic and neuropathic pain conditions.
However, a TID administration schedule may be difficult to sustain long-term, and no veterinary studies are currently published
on its use. However, anecdotally, BID administration does appear to achieve a clinical effect in dogs. Interestingly, in
a rat model there is recent evidence a gabapentin-like analog has reduced the development of experimental osteoarthritis.
The adverse effect of somnolescence can be mitigated by starting off at quite low doses and tapering upwards. Pregabelin
(Lyrica) is new generation compound, labeled for use in diabetic neuropathy and post-herpetic neuralgia; its utility in animals
remains unknown at this time.