Managing Difficult Pain Cases: Neuropathic Pain & Wind-Up Phenomenon
World Small Animal Veterinary Association World Congress Proceedings, 2013
Nancy Shaffran, CVT, VTS (ECC)
Erwinna, PA, USA

The options for analgesia are ever increasing as our understanding of pain physiology improves. Choosing the correct analgesic therapy requires an understanding of both the pharmacokinetics of a wide range of drugs, as well as the levels or type of pain associated with various conditions. The basic principles of current pain management include preemptive (preventative) analgesia, multimodal (using different classes of drugs simultaneously to interrupt the pain pathway at various points) and appropriate follow-up analgesia (postop and take home).The four traditional categories of drugs, NSAIDs, local anesthetics, opioids and alpha 2 agonists, are still used in various combinations to inhibit the nociceptive process at more than one site. More recently, several classes of drugs have been added to the pain management regime as adjunctive therapy in non-responsive cases. This includes NMDA receptor antagonists, anticonvulsants and antidepressants. No doubt as we learn more about wind-up phenomenon and the specific roles of various receptors, pain management will continue to be refined to allow for strategies, which prevent pain and maximize pain control, while reducing unwanted side effects.

Neuropathic Pain

Pain has traditionally been subdivided into acute and chronic, where acute pain is described as a sharp stabbing sensation, and chronic as dull persistent throbbing. It may be more appropriate to classify pain as inflammatory (with subsets of acute and chronic) or neuropathic (existing in the nerves irrespective of ongoing inflammation). Neuropathic pain can exist along with inflammatory pain or as a separate syndrome and is described as persistent burning, itching or tingling sensation with or without present cause. Treating neuropathic pain has allowed patients to return to a state of normal or near normal by ameliorating these signs. The most common neuropathic pain reliever used in veterinary medicine in Gabapentin (Neurontin®).

Gabapentin (anticonvulsant) plays a role in reducing neuropathic pain and central sensitization in chronic pain patients. Gabapentin is becoming increasingly popular in both human and veterinary medicine as the first choice in patients whose pain does not respond to conventional therapies, especially where nerve involvement is presumed. The primary indication for using gabapentin as an analgesic is to treat neuropathic pain. However, gabapentin has been effective in treating chronic pain, which was not considered to be neuropathic pain in humans & other animals. This suggests that neuropathic pain may be a component of some chronic/complex pain cases. The indications for initiating gabapentin therapy include:

 Chronic degenerative conditions such as osteoarthritis and cancer

 Dermatologic conditions such as lick granuloma, chronic skin or ear infections

 Persistent biting, licking, chewing, scratching at body areas

 Resistance to being touched at unaffected body sites

 Limping or obvious signs of pain not associated with current inflammation

Typical starting dose is 5–10 mg/kg BID to TID PO. Patients should be reevaluated for response frequently and dose adjustments are usually made every 3–5 days. Sleepiness is the side effect most commonly reported at higher doses. Caution: Neurontin® elixir contains xylitol.

Wind-Up Phenomenon

Wind-up phenomenon is a very important, newly understood concept in pain management. The vast majority of patients experiencing acute pain can be managed with conventional analgesics, such as NSAIDs, opioids and local anesthetics, but patients whose pain is unmanaged or who present in preexisting pain states may require additional therapy. Many patients stop responding to common analgesic drugs due to spinal cord wind-up.

The central nervous system adapts adversely to repetitive pain impulses after prolonged stimulation of nociceptors. This can cause a profound effect to the nervous system's architecture, thereby altering pain processing. When spinal neurons are subjected to repeat or high-intensity nociceptive impulses, they become progressively and increasingly excitable even after the stimulus is removed. This condition is known as central sensitization or wind-up phenomenon and leads to nonresponsive or chronic intractable pain. Wind-up is the culmination of two distinct phases of change in the nervous system. First, pain-transmitting nerve fiber threshold is reset. This resetting results in hyperalgesia, where less and less stimulation is required to initiate pain. In the second phase, nerve fibers that normally carry non painful information are recruited and become part of the pain-transmission process. This phase is termed allodynia and results in normally harmless sensations being interpreted as pain. The presence of hyperalgesia and allodynia collectively is considered wind-up phenomenon. This is apparent, for example, in the dachshund with disk disease that cries out in pain when any part of its body is touched, or the cocker spaniel with a chronic ear infection that can no longer tolerate normal petting. This phenomenon highlights the need for preemptive analgesia to treat pain before it begins and at regular intervals postoperatively.

Treatment or Prevention of Wind-up

Preemptive analgesics, prevention of spinal cord wind-up and administration of adequate analgesia early in the pain process are key in preventing long-term, chronic pain states. In addition to NSAIDs, gabapentin and/or amantadine have been quite effective in many patients. N-methyl-D-aspartate (NMDA) receptor antagonists, such as constant rate infusion of ketamine or oral administration of amantadine can enhance analgesia by blocking sensitization of neurons in the spinal cord and are especially useful for managing patients who have experienced wind-up phenomenon. Aggressive use of constant rate infusions before, during, and after painful surgery is essential in correcting or reversing severe spinal cord windup. See proceedings paper on CRIs for more information.


Speaker Information
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Nancy Shaffran, CVT, VTS (ECC)
Erwinna, PA, USA

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