How Neuropathic pain is an issue for Veterinarians

By Justin Bauer

Neuropathic pain occurs after a primary lesion or disease of the somatosensory nervous system (QUOTE). It can also develop due to mechanisms such as peripheral sensitization, central sensitization, impaired inhibitory modulation and pathologic activation of microglia. Many conditions affecting organs or tissue that possess nerve ending can also be the cause. The most common conditions reported include peripheral neuropathy, spinal cord disease, chronic musculoskeletal conditions, and brain lesions (Cavalli et al, 2019). The symptoms of neuropathic pain can include allodynia, hyperalgesia and paresthesia. The perceived pain occurs spontaneously and can manifest itself without any stimuli. Due to the lack of agreement on the definition of neuropathic pain, it is difficult to estimate the number of people affected by it, but it seems to be more prevalent among women and older people.

In general, somatosensory system disorders, such as neuropathic pain, are quite common in people with chronic neurologic and musculoskeletal diseases, however, these conditions are deadly to veterinary patients such as canines. Humans are easily able to self-report neuropathic pain whereas animals cannot do this. In addition to that, veterinarians have a limited background on neuropathic pain which makes recognizing these problems in patients difficult.

The peripheral aspect of neuropathic pain is characterized by a reduced threshold and the increased intrinsic excitability of peripheral nociceptor terminals. Typically, peripheral sensitization will resolve on its own as healing occurs. In certain scenarios it can persist and lead to physical alterations of function in primary afferent neurons. The focus lies on sodium channels, where an increased number of sodium channels will lower the stimulus threshold and result in neuropathic pain. Ectopic afferent activity references injury induced hyperexcitability which, unfortunately, generates aberrant action potentials in primary afferent neurons or in other sites in the nociceptive pathway. People affected by this mechanism often report spontaneous pain or paroxysmal shooting pain in the absence of an external stimulus. This type of activity is caused by sub-threshold oscillations in a resting membrane potential and result in bursts of rhythmic nerve depolarization without an appropriate stimulus. Many neuroinflammatory mechanisms such as microglial activations are implicated in the induction and maintenance of a chronic neuropathic pain state. Through an injury, microglia in the central nervous system become pathologically activated and subsequently respond by releasing inflammatory mediators. These in turn activate astrocytes and enhance the production of other inflammatory mediators.

Diagnosing neuropathic pain in animals is a huge part of the problem veterinarians face. Neuropathic pain in rodents can be assessed with quantitative sensory testing (QST), however, this technique is more common in laboratories than in actual clinical assessments. In order to diagnose a patient with this disorder, veterinarians will have to observe certain clinical signs either visually or through a report by an owner. Since the owners themselves might be unaware, veterinarians should inquire about possible signs that would indicate the patient is at risk. Certain signs could include “altered reaction to touch, vocalization in the absence of an overt painful stimulus, phantom scratching, excessive licking or self-mutilation, and persistent lameness/diminished weight-bearing on a limb”. However, subtle signs, such as decreased general activity level, general reluctance to climb or descend downstairs, changes in body posture, and altered appetite are also possible indications.

How is one able to treat this pain in animals? The effects of neuromodulatory drugs (such as the TCA) in managing neuropathic pain are distinct from their antidepressant effects (Attal , 2015). Amitriptyline for example, is a first-line therapy for humans, demonstrating efficacy in diseases like postherpetic neuralgia, poststroke pain, and chronic low back pain. TCA’s are able to exert analgesic effects in multiple ways, such as through inhibition of serotonin and norepinephrine reuptake, antagonism of voltage-gaited sodium channels, and ultimately antagonism of NMDA receptors. Unfortunately, no conclusive studies have been conducted yet to assess their use in dogs, with only mixed results reported so far. Another possible solution that had only shown mixed results is Amantadine, a NDMA antagonist. It can decrease central sensitization and opioid tolerance for some patience and is suspected of enhancing effects of NSAIDS, gabapentin, and opioids (Lamont, 2008).

To sum it up, neuropathic pain is an under-recognized condition in many veterinary patients with a lot of neuromusculoskeletal diseases. Certain drugs, such as gabapentin and pregabalin need controlled studies to evaluate their efficiency before they are implemented. All veterinarians can do at this time is to take the time to assess this disorder as a possible issue in patients. A broader approach to neuropathic pain in veterinary school would also help more veterinarians accurately assess and recognize patients’ symptoms.

References:

Moore, S., 2016. Managing Neuropathic Pain in Dogs. Frontiers in Veterinary Science, 3(2297-1769).

Attal N, Bouhassira D., (2015) . Pharmacotherapy of neuropathic pain: which drugs, which treatment algorithms? Pain 156(S1):S104–14.

Lamont L, (2008). Adjunctive analgesic therapy in veterinary medicine. Vet Clin North Am Small Animal Practice 38:1187–203.

Cavalli, Eugenio et al. “The neuropathic pain: An overview of the current treatment and future therapeutic approaches.” International journal of immunopathology and pharmacology vol. 33 (2019): 2058738419838383. doi:10.1177/2058738419838383

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