Pain management for laminitis is critically important in prevention of suffering. In addition, good pain control can enable treatment without causing further injuries to the horse. Owners often elect euthanasia because of severe and continuous pain. Both local and systemic analgesic techniques can be of benefit, the goal being a comfortable patient and minimal systemic effects.
The pain associated with laminitis is a result of three mechanisms: inflammation, facilitation of central pain transmission, and neuropathic pain. Inflammation is an important component of laminitic pain. Many of the chemical mediators of inflammation, such as complement, kinins, cytokines, and eicosanoids, that have been identified in the laminitic hoof can enhance the responsiveness of the high-threshold C nociceptive fibers through two mechanisms. First, the normally high threshold of nociceptors is decreased during inflammation; and second, the frequency of activation increases in proportion to the local concentration of inflammatory mediators. This increase in peripheral nociceptor responsiveness is often termed peripheral sensitization. Central sensitization is the facilitation of pain transmission within the central nervous system. This is a result of the increased excitability of spinal synapses caused by release of excitatory chemicals such as glutamate, substance P, prostaglandins, cytokines, and others. Neuropathic pain is indicated by the presence of chemical markers of nerve injury in the lateral digital nerves of laminitic horses. The dorsal root ganglia associated with these nerves also have increased expression of activating transcription factor and neuropeptide Y, which results in increased autonomous activity of these spinal nerves through a variety of mechanisms, including loss of normal dorsal horn inhibition, increased coupling of sympathetic and nociceptive activity (stress potentiates the pain), increased expression of sodium channels in the dorsal root ganglion, and increased sensitivity to localized excitatory products.
It is also important to consider the progression of the source of pain during the disease. In the first 48 to 72 hours of clinical signs, the pain is primarily caused by inflammation and primary nociceptive receptor stimulation. As the disease progresses and becomes more chronic, peripheral and central sensitization and neuropathic pain become progressively more important. With these mechanisms in mind, it is important to consider how different analgesics can be used to ameliorate laminitic pain.
Systemically Administered Analgesics
Systemic administration of analgesic drugs is often the mainstay of laminitis pain control. Several classes of drugs are commonly used: nonsteroidal antiinflammatory drugs (NSAIDs), α2-receptor agonists, opioids, lidocaine, gabapentin, and ketamine. α2-Receptor agonist drugs are not usually used as long-term systemic analgesics because of their undesirable adverse effects.
Nonsteroidal Antiinflammatory Drugs
Nonsteroidal antiinflammatory drugs are a critical component of analgesia in horses, and their use is well understood, so discussion of this class of drugs will be limited to a few specific comments. Stacking, the concurrent use of multiple NSAIDs, does not improve the effectiveness of NSAIDs and may potentiate the undesirable effects. Generally, cyclooxygenase-2–specific drugs such as firocoxib should elicit fewer adverse effects, especially in the face of stress and chronic administration. In reality, this distinction is not clear-cut, and different horses may have different responses with regard to drug efficacy and severity of side effects.
Opioids modulate pain transmission through activation of a G-protein-coupled receptor family in the central nervous system. Binding of an opioid agonist to a receptor ultimately results in decreased neuronal excitability, which results in attenuation of the nociceptive signal as it is transmitted centrally. This decrease in excitability occurs both presynaptically and postsynaptically. Opioids work within the brain to decrease pain perception and activate various descending antinociceptive pathways. There is also increasing evidence of peripheral opioid receptor activity in injured tissue that is probably triggered, at least in part, by inflammation. The activity of these peripheral opioid receptors increases in the first 1 to 3 days after injury, through either increased activity of receptors already present or migration of receptors down afferent neurons.
Opioids can be used intermittently or as a continuous intravenous infusion, with the latter administration route yielding superior analgesia with fewer undesirable systemic effects. The most commonly used opioid is butorphanol, which is administered at the rate of 13 to 24 µg/kg/hour after a loading dose of 18 µg/kg has been given. Buprenorphine has also been useful when administered twice daily at a dose of 0.005 mg/kg, intravenously or intramuscularly. At this dose of buprenorphine, some mild excitement and decreased gastric motility occurs. Other opioids such as fentanyl or morphine have been used primarily as an adjunct to general anesthesia or in sedation protocols used in the standing horse. One other opioid delivery system, transdermal fentanyl patches, has been used as a chronic analgesic delivery system. Results are variable. Typically, one 100-µg/hour patch is used for each 150 kilograms of body weight. The patches are applied to dry, clean, clipped or shaved areas. It takes several hours for the patches to yield effective plasma levels, and patches last for 48 to 72 hours.
Epidural administration of opioids works well in inducing analgesia in the hind limbs, and an epidural typically provides 12 to 18 hours of analgesia. Morphine is the opioid most commonly used and is given at a dosage of 0.1 to 0.2 mg/kg. Epidural buprenorphine has also been used in horses at a dosage of 0.005 mg/kg. The addition of 15 to 30 µg/kg of detomidine may increase the effectiveness and duration of analgesia provided by the morphine or buprenorphine. If repeated doses are to be administered, an epidural catheter can be placed. The introducer needle is placed in a manner similar to a conventional caudal epidural, and when the tip of the Touhy needle enters the epidural space, the catheter is advanced cranially for a distance of about 10 cm. The catheter is then secured to the patient. The author prefers to use the non–coil-reinforced catheters because they can be shortened to ease maintenance.