What's new in small animal analgesia? (Proceedings)

Pain management in small animal medicine is one of the fastest growing areas of revenue. Veterinarians should be knowledgeable about pain management because not only is it good medicine, clients think we already know about it and are doing something for their pets, our technicians are talking to each other about pain and our treatment of it, It is become standard of care in most setting, for example the American Animal Hospital Association has standards that address it, and animal law will start to impact how we treat our patients.ttorneys think clients care about it.

Analgesia is complete absence of pain. Clinically, the analgesia that we are trying to achieve is a reduction in perceived pain. Pain has a very complex pathophysiology and treatments can be different for different types of pain. For example, an analgesic plan for a patient with acute surgical pain may be very different from an animal with chronic osteoarthritic pain. It is also important to recognize that anesthesia is not pain control. Although the brain does not perceive inflicted pain, central sensitization of the spinal cord still occurs and can result in a chronic pain state.

Multimodal Analgesia is the use of two or more classes of analgesic drugs to target multiple mechanisms or pathways in the pain experience to reduce the overall amount of pain perceived by a patient. At a type of pain increases or persists, additional medications can be added.

Non-steroidal anti-inflammatory drugs (NSAIDs) is one of the fastest growing areas of research, use, and revenue generation in veterinary medicine. Many NSAIDs are available for labeled and off label use. Care must be taken with patient selection, NSAID selected, and washout periods between use. The introduction of COX-1 sparing NSAIDs does not improve their overall safety profile and may come down to patient individual response.

Tramadol is centrally acting synthetic opioid whose mechanism of action is not completely understood. The parent compound has low affinity to µ opioid receptor, however the O-demethylated metabolite M1 has higher affinity and is 6 times more potent as an analgesic with 200 times more potent binding to µ receptor. Tramadol also acts as a weak inhibition of re-uptake of norepinephrine and serotonin and its analgesic effect seems to be independent of opioid action. Tramadol has a bioavailabliltiy of 65% and oral dosages of 5 mg/kg q6h and 2.5 mg/kg q4h resulted in tramadol and M1 plasma concentrations consistent with analgesia in humans. More efficacy studies at these doses needed. Tramadol can have pronounced effect in cats causing euphoria, dilated pupils, and sedation. At a dose of 1 mg/kg, tramadol did not produce thermal or mechanical antinociception in cats. Tramadol is indicated for mild to moderate pain in dogs.

Gabapentin has gained popularity as an analgesic in dogs and cats, however its exact mechanism for analgesia is unknown. Its therapeutic action on neuropathic pain is thought to involve voltage-gated N-type calcium ion channels. It binds to the α2δ subunit of the voltage-dependent calcium channel in the central nervous system. Gabapentin has a structure similar to GABA and was originally designed for anti-epileptic use. As an analgesic it prevents allodynia and hyperalgesia and inhibits signaling in the dorsal horn of the spinal cord in a dose-dependent fashion. It is best suited for combination therapy in chronic pain states or neuropathic pain at dosages in dogs at 2-10 mg/kg PO BID to QID and in cats at 2-5 mg/kg PO BID.

Amantadine was originally developed as an antiviral drug. It has also been shown to be a NMDA antagonist activity in spinal cord and may be suitable for use in patients with allodynia and opioid tolerance. When used in patients with chronic pain, it can lower opioid doses and can also be used in treatment of neuropathic pain. Dosages used in dogs include 3 to 5 mg/kg PO q 24h. Bhavioral changes occur at doses greater than 15 mg/kg and the toxic dose in cats is 30 mg/kg.

Dextramethorphan is a common over-the-counter cough suppressant that also inhibits NMDA receptors in the spinal cord. It was thought that it could be used similar to amantadine. However, rapid metabolism in dogs may limit its usefulness.

Fentanyl Patches provide a highly lipid soluble, short-acting opioid released at a constant rate. The patches are designed for human skin and uptake in veterinary patients in highly variable. Hair, skin thickness, temperature, and skin preparation can all affect uptake. Additionally, fentanyl patches are not appropriate as a sole treatment for acute surgical pain.

Liposomal encapsulated opioids allow for a slow efflux of drug, which is controlled via the drugs lipid solubility and polarity. Over time degradation of liposome occurs through lipases and the degraded material is removed by phagocytes. The end result is the slow release of drug into systemic circulation and avoids peaks and troughs of plasma levels. Both oxymorphone and hydromorphone have been used experimentally and shown promising results. A three day duration of action encapsulated fentanyl is rumored to be entering the market soon. DepoDur™ is a liposomal encapsulated morphine that has FDA approved for epidural use in humans. It provided greater than 48 hours of analgesia after hip or knee surgery in humans. It also provides up to 3 days of analgesia after epidural use in rats and dogs. Up to 6 days of analgesia in rats has been demonstrated after SC injection. However, at this time it is cost prohibitive in veterinary patients. Long acting buprenorphine is currently available.

The use of Opioid in cats has always been somewhat controversial. Opioid mania, or paradoxical excitement has been an issue in the past but is probably related to high doses causing the altered behavior. Morphine doses less than 0.2 mg/kg tends to limit these behavior effects while still providing analgesia. The combined use of butophanol and hydormorphone in interesting because although it does not result in profound sedation, it can elicit at behavior change in cats that is calming. Analgesia is not a strong as hydromorphone alone but lasts up to 8 hours. Opioid associated hyperthermia is a known side effect in cats and most commonly associated with Hydromorphone. It is thought to be dysregulation of thermoregulatory center and results in elevated post anesthetic temperature as high as 107°F. This elevated temperature is non-responsive to NSAIDs and tends to normalized over time. In general, the elevated temperature peaks at 2 hours post anesthesia and can be treated by reversal of opioid. Buprenorphine is a partial mu agonist opioid that provides adequate analgesia for mild to moderate pain. The duration of action is 6 to 8 hours. It can be administered IV, IM, SQ, but in cats, it has a unique buccal administration with almost 100% bioavailability.

Future areas of analgesia include a ketamine patch the use of the neurotoxins resiniferatoxin (RTX) and a substance P – saporin conjugate.

Maropitant Citrate (Cerenia™) is a drug indicated for acute canine emesis. It is available in tablet and injectable formulations. It can be used to help reduce vomiting associated with opioid administration and may have some analgesic properties. Its mechanism of action involves binding NK-1 receptors in the emetic center and chemoreceptor trigger zone (CRTZ). It has also been shown to reduce the MAC of sevoflurane 24 to 30% when administered at a 1 mg/kg loading dose and a 30 µg/kg/hr IV infusion.

Nonpharmacologic approaches to analgesia should also be considered and include physical medicine modalities such as nursing care, acupuncture (TENS), laser therapy, massage therapy (trigger point), joint mobilization / exercise therapy, thermotherapy, ultrasound therapy, hydrotherapy, and environmental analgesia.