Introduction

  • The growth in scientific knowledge of the pathophysiology of pain Pain  Pain: assessment in small animals allows us to select a wide variety of pharmaceutical agents combined with other techniques for pain management. Pain management can be divided into 2 very broad categories: acute and chronic pain control. This article primarily discusses pain management drugs and includes recent information and developments. 
  • The goal of pain management for trauma patients is to immediately alleviate the intensity of pain by administering appropriate primary analgesics. This usually involves opioids in combination with sedatives.
  • The goal of acute pain management for patients undergoing elective surgery is to prevent pain by using analgesics Analgesia: overview pre-emptively, intra-operatively, and postoperatively according to need. This usually involves one, or a combination of the following: opioids Analgesia: opioid; local anesthetics Local anesthesia: overview; constant rate of infusion with an NMDA (N-methyl-D-aspartate) receptor antagonist, opioids, and local anesthetics; and NSAIDs (non-steroidal anti-inflammatory drugs) Analgesia: NSAID.
  • The goal of managing non-malignant chronic pain is not only to alleviate pain daily but also to improve the function of the patient over time and improve quality of life. This may involve the use of opioids, NSAIDs, tramadol, and drugs used to treat neuropathetic pain, such as amantadine Amantadine, gabapentin Gabapentin, and NMDA receptor antagonists.
  • The goal of managing malignant pain is to provide comfort and may involve using the whole spectrum of analgesics and sedative agents over the course of the disease.
  • Using various analgesic agents at different times or in different combinations may drastically improve the quality of pain management. Strategies such as pre-emptive analgesia and balanced analgesia (or multimodal analgesia) are frequently used. 
  • Pre-emptive analgesia operates on the principle of administering analgesic drugs before the painful stimulation occurs, thereby preventing central nervous system sensitization (or wind up), which amplifies the sensation of pain. The use of the balanced analgesic technique allows practitioners to use the various mechanisms of action of the different analgesic agents to provide pain control, minimizing the side-effects of a single large-dose of any one analgesic agent. The use of various low-dose analgesic agents may also provide synergistic analgesic effects, benefiting the patient more than a single analgesic agent.

Pre-emptive analgesia and premedication

  • Opioids remain the most commonly used analgesic agents. 
  • Opioids such as butorphanol Butorphanol tartrate (0.2 mg/kg), buprenorphine Buprenorphine (10-20 µg/kg), morphine Morphine (0.25-0.5 mg/kg), methadone Methadone (0.1-0.5 m g/kg), hydromorphone Hydromorphone (0.05-0.1 mg/kg), and fentanyl Fentanyl (parenteral) (5-10 µg/kg) are commonly used in dogs and cats.
  • The advantages of using these opioids as part of a premedication protocol are:
  • To provide mild-to-moderate sedation Anesthetic premedication: overview in addition to the analgesic effect.
  • To help reduce the  induction and maintenance anesthetic requirements Anesthetic induction: overview.
  • Administering these opioids intravenously following induction of anesthesia will have a sparing effect on the maintenance anesthetic agents. 
  • A neuroleptic analgesic combination can be used in dogs and cats before induction of anesthesia. The opioids can be combined with either acepromazine Acepromazine maleate (0.025-0.1 mg/kg, IM); medetomidine Medetomidine (0.008-0.04 mg/kg, IM), dexmedetomidine Dexmedetomidine (0.004-0.02 mg/kg IM); or midazolam Midazolam (0.2-0.4 mg/kg, IM). The use of acepromazine and (dex)medetomidine should be reserved for healthy patients. For diseased or depressed patients, the use of an opioid alone or in combination with midazolam will provide reasonable sedation with analgesia. A micro-dose of medetomidine (3-5 µg/kg, IM) or dexmedetomidine (1-2 µg/kg, IM or IV) can be administered to enhance sedation induced by a midazolam-opioid combination.

Combination of opioids and NSAIDs for pre-emptive analgesia

  • It has been well documented that combining opioids and NSAIDs produces analgesia that is far greater than either drug used alone.
  • Injectable NSAIDs, such as robenacoxib Robenacoxib, carprofen Carprofen, meloxicam Meloxicam, or ketoprofen Ketoprofen offer several significant advantages over oral NSAIDs in acute pain management Therapeutics: musculoskeletal system.
  • Injectable NSAIDs can be used as part of the premedication administered with other neuroleptic-analgesic premedicants prior to anesthesia induction.
  • Alternatively, injectable NSAIDs can be administered in dogs and cats either after anesthesia induction but prior to surgical stimulation or after the surgery but prior to extubation.
  • Oral NSAIDs, such as cimicoxib, deracoxib, firocoxib, etodolac (all licensed for administration to dogs) can only be used prior to the premedication when the patient is conscious and able to swallow. When administering an oral NSAID for premedication in dogs and cats, caution should be taken to prevent a vomiting response following opioid premedication. The NSAID administered orally may be regurgitated before taking its full action.
    Practitioners can use injectable NSAIDs for acute pain management while the patient is in the hospital and then follow up with oral NSAIDs postoperatively as part of the take-home medication.
  • Several precautions should be taken when using NSAIDs as pre-emptive analgesics with anesthesia and surgery.
    Avoid NSAIDs in patients with dehydration or in anticipation of significant blood loss. 
    Some NSAIDs may potentate intra-operative bleeding, as well as induce renal damage when combined with general anesthetic agents in the face of hypotension.
    Therefore, using NSAIDs with general anesthetics should be limited to the patients that do not have a bleeding disorder or renal dysfunction. 
  • Other precautions when using NSAIDs as part of the pain management protocol include avoiding their use in dogs and cats with liver, kidney, and gastrointestinal (GI) dysfunctions.
    Patients recently receiving steroid drugs should not receive NSAIDs as part of their pain management for fear of potential GI ulceration-perforation.
    If there is any doubt regarding the contraindications of using NSAIDs, other alternatives, such as opioids, should be used instead.

Regional anesthesia-analgesia techniques and local infiltration

  • Local anesthetics can play a vital role in small animal pain management.  Regional anesthesia techniques Local anesthesia: overview for soft-tissue, orthopedic, and dentistry cases have practical applications. For hindquarter soft-tissue and orthopedic surgical procedures in dogs and cats, epidural Anesthesia: epidural administration of preservative-free morphine and bupivacaine Bupivacaine at the lumbo-sacral junction prior to the surgical procedure will alleviate pain both intraoperatively and postoperatively. For any front-limb orthopedic (radial or ulna fracture repair) or toe amputation or soft-tissue (tumor or growth removal) surgery, a brachial plexus nerve block using bupivacaine (0.5%-0.75%) provides extensive analgesia to the front limb from the shoulder distal to the toe. 
  • Another technique is called the Bier block Local anesthesia: intravenous regional anesthesia (IVRA) which utilizes a tourniquet applied proximal to the surgical site, preventing blood circulation distal to the extremity. Lidocaine Lidocaine is then injected into the vein of the extremity distal to the tourniquet. The lidocaine is "retained" in the local blood circulation and eventually diffuses across blood vessels to desensitize the local nerves. This technique should not be used in the diabetic patient. The duration of surgery should be limited to approximately 60 mins, and the local anesthetic used should be free of epinephrine to avoid ischemia of the local tissue. 
  • A combination of lidocaine (2%) and bupivacaine (0.5%) in a syringe at equal volumes provides a faster onset of effect than lidocaine and a longer analgesic duration (6-8 hours) than bupivacaine. This lidocaine-bupivacaine mixture at approximately 0.2 ml per site can be used to perform a ring block or specific blocks for cat declaws or dental blocks at the mental and infra-orbital foramens to provide a long duration of analgesia.
  • For thoracotomy Thorax: thoracotomy (intercostal) pain relief, 3 injections of 0.5% bupivacaine or a combination of lidocaine (2%) and bupivacaine (0.5%) at 0.2-0.5 ml per site should be administered at the intercostal space where the nerves come out of the lateral spinal process. One injection should be at the incision site, the second should be anterior to and the third should be posterior to the incision line. These will desensitize the intercostal nerves and alleviate incisional pain.  
  • For other types of soft tissue surgeries, a combination of bupivacaine and lidocaine can be used for an infiltration block either prior to surgery or after completion of the surgical closure. 

Constant rate of infusion

  • Fentanyl, morphine, ketamine, and/or lidocaine have been used for constant rate of infusion (CRI) perioperatively. Opioid CRI provides pre-emptive analgesia, reduces the total general anesthetic required and provides postoperative analgesia. The sparing effect is especially useful for critically ill patients, when the cardiovascular depressive effects of an inhalant can be alleviated with lower doses of inhalant.  
    Be aware that lidocaine given by CRI during anesthesia is noted to cause significant cardiovascular depression in cats and is not recommended. 
  • The use of a low-dose ketamine infusion (2-10 µg/kg/min) intraoperatively improves postoperative analgesia. The analgesic mechanism of this is presumably because ketamine is an NMDA receptor antagonist that inhibits central sensitization. This concept has lead to the recent use of a low-dose ketamine infusion with or without an opioid in veterinary pain management. A combination of ketamine and opioids for CRI is another example of balanced analgesia or multimodal analgesia, in which a combination of both drugs work additively or synergistically to provide a more profound analgesia than either drug alone.
  • Morphine (60 mg) can be mixed with ketamine (60 mg) in 1000 ml of a balanced electrolyte solution and administered as a CRI (at a rate of 1-2 µ/kg/min) from the beginning of the surgery to the conclusion of anesthesia.  In some painful surgery cases, the CRI may be continued into the recovery period for up to several days post surgery. 
  • The use of micro-dose medetomidine (50 µg in 500 ml balanced electrolyte) for CRI adds an additional dimension to the ketamine, morphine, ketamine-morphine combination CRI. The principle of adding a micro-dose of medetomidine to either ketamine or morphine CRI is to induce sedation and further enhance the analgesic action of ketamine and morphine. Using ketamine or morphine CRI for an extensive period frequently induces dysphoria in some dogs and cats. Adding medetomidine as part of the CRI, greatly reduces the frequency of dysphoria and keeps the animal calm. Micro-dose medetomidine CRI also reduces the inhalant requirement during the surgery and provides a smooth recovery in both dogs and cats. Medetomidine can be substituted with dexmedetomidine at 50% of the medetomidine dose rate.