Pain recognition and treatment has come to the center of Veterinary Science in the last ten years.

Acute pain is often studied and discussed in the perioperative setting, and chronic or neuropathic pain is often discussed in the osteoarthritis setting. As a result, these important aspects of pain management are the most comfortable for most practitioners. Some of the less mainstream conditions of importance are in need of more comfort and confidence. This is especially true in the ICU, where both surgical and medical sources of pain abound, and immune systems are taxed even without the additional burden of unmanaged pain.

Pain is often categorized into three categories that tend to be experienced differently and respond to treatments differently. These three categories are nociceptive, inflammatory, and neuropathic. Often, especially in longer-lasting or chronic pain there is overlap between these categories. There is no predictable link between duration or intensity of injury that will then progress to chronic or neuropathic pain. Even the 'simplest' surgical procedures can sometimes progress to chronic pain in people, and we have to be vigilant for the same phenomenon in dogs and cats. At the current time, the best approach we have toward combating chronic or neuropathic pain is in dealing aggressively with pain at the time of sickness and injury.

Ill and injured patients are often metabolically and cardiovascularly challenged, so treating pain becomes more risky. These patients may be extremely susceptible to sedative and other systemic side effects of medication, and yet treating their pain is critically important to avoid further depression of their immune system and healing capacity. As such, individualized pain assessment and carefully titrated application of integrated methods of pain control are vital. This is not the situation where a protocol (such as NSAIDs and tramadol after a TPLO) is an effective or safe option.

The first step in defining an analgesic plan for critically ill patients lies in assessing the pain. While pain behaviors are fairly well described in dogs and cats (see Guidelines for Recognition, Assessment and Treatment of Pain. J Small Anim Pract. 2014, http://onlinelibrary.wiley.com/doi/10.1111/jsap.12200/abstract) critically ill patients may have other reasons for expressing many of these behaviors. For instance, hemodynamically unstable patients and patients with brain injury are unlikely to be appropriately interactive, and this is a major component of pain assessment. It is therefore critically important to have a sense of the level of pain associated with different conditions, gathered both from experienced clinicians and also from extrapolation from the speaking primates. The list below attempts to gather conditions into a broad category of level of pain, and it is also printed in the WSAVA global pain treatise (referenced above).

Perceived Level of Pain Associated with Various Conditions

The designation of conditions into categories below is intended to serve only as a guide. Pain may vary according to the patient and the condition. Each patient should be assessed individually.

Severe-to-Excruciating

 Central nervous system infarction/tumors

 Meningitis

 Fracture repair where extensive soft-tissue injury exists

 Spinal surgery

 Ear canal ablation

 Burn injury

 Articular or pathological fractures

 Limb amputation

 Necrotizing pancreatitis or cholecystitis

 Thrombosis/ischemia

 Bone cancer

 Hypertrophic osteodystrophy

 Aortic saddle thrombosis

 Neuropathic pain (nerve entrapment/inflammation, acute intervertebral disc herniation)

 Inflammation (extensive e.g., peritonitis, fasciitis - especially streptococcal, cellulitis)

Moderate-to-Severe (Varies with Degree of Illness or Injury)

 Immune-mediated arthritis

 Panosteitis

 Capsular pain due to organomegaly

 Hollow organ distension

 Traumatic diaphragmatic rupture

 Pleuritis

 Trauma (i.e., orthopaedic, extensive soft tissue, head)

 Frostbite

 Ureteral/urethral/biliary obstruction

 Glaucoma

 Corneal abrasion/ulceration

 Uveitis

 Early or resolving stages of soft-tissue injuries/inflammation/disease

 Intervertebral disc disease

 Mesenteric, gastric, testicular or other torsions

 Peritonitis with septic abdomen

 Mucositis

 Oral cancer

 Mastitis

 Dystocia

 Extensive resection and reconstruction for mass removal and corrective orthopaedic surgery (osteotomies, cruciate surgery, open arthrotomies)

Moderate

 Soft-tissue injuries (i.e., less severe than above)

 Urethral obstruction

 Ovariohysterectomy

 Cystitis

 Diagnostic arthroscopy and laparoscopy

 Osteoarthritis

Mild-to-Moderate

 Dental disease

 Otitis

 Superficial lacerations

 Mild cystitis

 Chest drains

 Abscess lancing

 Castration

When treating pain in the critical care environment, it is imperative to titrate medications, assess the response to the treatment, and then repeat (ad nauseam, if necessary). Patient assessment includes physiological (not reducing respiratory or cardiac function too excessively, avoiding predictable toxicity and side effects) and behavioural (reducing agitation, improving sleep, controlling dysphoria) parameters.

A brief summary of the pharmacologic options for treating pain in the ICU is below, but an understanding of the drugs, side effects and reactions is vitally important and cannot be covered in detail in this lecture.

 Opioids are the cornerstone of pain treatment in the hospitalized patient. There are several different drugs to choose between that all come with individual pros and cons, onsets and durations. Major considerations for using opioids in the ICU include the good things (easy to titrate, reversible, minimal cardiovascular depression, effective, mildly sedating) and the bad things (sedating, difficulty in discerning pain from opioid dysphoria, respiratory depression, increased glial reactivity with possible contribution to neuroinflammatory chronic pain when used alone).

 Nonsteroidal anti-inflammatory drugs have a Jekyll and Hyde personality in the ICU. A tremendous number of conditions have an inflammatory component that contributes vastly to the pain (both acute and chronic conditions). Providing anti-inflammatory relief is highly effective and is actually the first tier of treatment in the human medical paradigm. These drugs also do not generally increase sedation, which is a very valuable tool in patients where sedation is an important confounder to metabolic/cardiovascular/neurologic decline. However, the potential for organ damage (GI, renal, hepatic) is a hugely important consideration and inevitably limits the number of ill or injured dogs and cats that can safely be administered NSAIDs. Once cardiovascular stability and GI health are stabilized and deemed likely to remain stable, NSAIDs can (and should) be considered.

 Alpha₂ adrenoceptor agonists are profound sedative and analgesic drugs. The utility of dexmedetomidine (in particular) to be used as a constant rate infusion in some critically ill patients has been increasingly reported. As with NSAIDs, the decision to use these medications on a particular patient has to be thoroughly evaluated, as the cardiovascular depressant effects of α₂ agonists are marked. Microdosing is absolutely required when used in this environment, but can be extremely effective at augmenting analgesia. Significant sedation is expected with the use of these drugs, but where appropriate this is an advantage, especially because dysphoria is not seen and can be mitigated by their use. A further consideration for the use of α₂ agonists is that, although they are reversible, the reversal drugs have been associated with independent cardiovascular effects that can be catastrophic in severely compromised patients, so reversal is not always an option when a crisis occurs.

 Local anesthetics are generally used peripherally/regionally, but lidocaine has also been used systemically. These drugs are generally quite safe within defined dosage ranges, and have the advantage of being both anti-inflammatory (perhaps even radical scavenging) and analgesic. Used within these limits, local anesthetics are extremely safe and should be considered in every patient. Disadvantages include increased vigilance to prevent burns/wounds to insensitive regions, vasodilation when large regions are blocked, and need to repeat administration frequently. Some tissues are sensitive to repeated doses of local anesthetics and should not be included in repeated administrations of local blocks (cornea, intra-articular, and immediately perineural).

 Adjunctive medications can be extremely helpful for managing the critically ill patient. At the top of this list is NMDA receptor antagonists (ketamine, amantadine, methadone). These medications are generally cardiovascular sparing, reduce or eliminate opioid-induced hyperalgesia (glial-mediated neuroinflammation) and have limited impact on mentation.

 Gabapentin is another medication that is generally more established for use in chronic pain. Patients that have a component of chronic or neuropathic pain to their presentation are excellent candidates for gabapentin or pregabalin. Furthermore, increasing data support some mild to moderate efficacy for more acute conditions, although there are still a lot of controversy and mixed data for this use. Cardiovascular sparing, these medications do change mentation and may contribute to ataxia. Therefore, as with all medications in this population (except perhaps the opioids), individual decision making is imperative. A few other medications may augment analgesia in certain groups of patients. This includes maropitant (antiemetic) which may have some visceral analgesic qualities (insufficient to be used as a sole analgesic) and serotonin/norepinephrine modifiers such as amitriptyline, clomipramine and tramadol. Drugs in this category are generally insufficient when used alone, but may be useful to supplement analgesia in difficult cases.

Finally, every patient has an intrinsic pharmacopeia in their innate physiology, and non-drug techniques to augment analgesia tend to have minimal side effects and may be markedly effective when combined with drug modalities. No patient in the ICU should go without a menu of physical medicine adjuvants to their chemical protocols.

 Acupuncture is understood to work through neuromodulation along the majority of innate pain-modifying and immune-modifying pathways. In trained hands, acupuncture has virtually no negative side effects and can be a potent tool for promoting analgesia, gastrointestinal motility and immune modulation.

 Laser therapy is a safe and noninvasive tool for increasing local blood flow, providing local and regional analgesia and increasing the rate of tissue healing.

 Touch and massage have been shown to provide comfort and analgesia across species, while improving local blood flow and relieving secondary sources of pain from medical conditions, recumbency, and procedures.

 Heat improves local tissue blood flow and helps release soft-tissue restrictions.

 Cooling decreases pain sensation, edema formation, and peripheral hypersensitivity.

 Motion (titrated carefully by trained individuals) such as walking, supported standing, range of motion, swimming, etc. have been shown to augment analgesia; improve fluid dynamics in soft tissues such as intervertebral disks, joints, tendons, ligaments, muscles and fascia; reduce soft-tissue contracture and speed recoveries.

 Nursing and supportive care to provide regular rotation during recumbency, warmth, touch, interaction, and comfort are also critical to recovery and should be considered a chartable form of therapy, similar to any medication.

In the end, multimodal analgesia in the injured dog or cat involves a deep understanding of pain physiology, pathophysiology of the patient's condition, a strong grasp of pharmacology and the inherent challenges posed by the use of different drugs, and a strong program of empathetic and responsive physical medicine applications. The outcomes from this comprehensive approach are phenomenal, and the least that we can do to help augment short-term recovery and also reduce the incidence of long-term pain and dysfunction in our patients.