Managing chronic pain

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When it comes to pain, understanding the different types is the first step to targeting and treating patients. Acute pain, if left unmanaged, can become chronic, which can lead to changes in the neuronal system and a constant state of nociceptive input, even in the absence of a noxious stimulus. S. Bryce Dooley, DVM, MS, DACVAA, founder of Allied Veterinary Anesthesia Associated in Philadelphia, Pennsylvania, broke down the options available to veterinary professionals for targeting multiple aspects of pain in her lecture “Beyond the NSAIDS – A Multimodal Approach to Chronic Pain,” delivered at the 2023 Directions in Veterinary Medicine symposium in Miami, Florida.

NMDA antagonists-ketamine and amantadine

Dooley informed attendees that the NMDA antagonists ketamine and amantadine are helpful to pets suffering from acute, chronic, cancer, and neuropathic pain. This class of drugs works by decreasing excitatory neurotransmitters at the spinal cord. They also activate opioid receptors and the endocannabinoid system, all playing a central role in preventing or reducing pain. Dooley also encouraged attendees to not be afraid of using ketamine on patients.

“This would probably be my go-to, whether that's going to be ketamine in hospital for like a wind down infusion for these intractable pain situations. It may not be an osteoarthritis patient, but say, a nerve sheath tumor pain or something that [is] so painful you can't even touch a dog,” explained Dooley.

"We actually just had [a suspected nerve sheath tumor patient] in the hospital the other week, and we put them on ketamine, and it really, really helped. What [the NMDA antagonists ketamine and amantadine] do [is] prevent glutamate binding right at the dorsal horn spinal cord with glutamate [being] one of the big excitatory neurotransmitter that sends the impulses to the CNS [to] help the brain recognize things as pain," she continued.

For chronic pain patients, outpatient ketamine injections are a potential option. When adding amantadine as a treatment for patients, Dooley warned attendees that it may take a little time to kick in, so to wait at least 48 to 72 hours to start seeing effects. For patients that are suffering from osteoarthritis, both dogs and cats have had drastic improvements in their mobility with amantadine.

Alpha2 agonists

Alpha2 Agonists provide analgesia, amnesia, and sedation through decreased norepinephrine release at Alpah2a, b, and c receptors. Alpha2 agonists increase mechanical nociceptive thresholds by augmenting the descending pathway when provided to patients systemically.² According to Dooley, when lower doses and slower infusions are used, the undesirable cardiovascular side effects can be avoided.

“Alpha2s are really, really interesting. They have a multitude of effects. So, you can see that they will inhibit our nociceptive fibers peripherally, but they also have some modulating effects at the dorsal horn of the spinal cord. They also affect the supraspinal perception of pain and again, enhance that descending pain pathway. It can really be used for any type of pain [such as] acute pain, inflammatory pain, chronic pain,” said Dooley.

Dooley continued to explain that with a multimodal approach, alpha2 agonists are an effective way to provide pain relief. However, their use is somewhat limited to in-hospital use until further studies are performed.

Conclusion

Preemptive multimodal analgesia is crucial for patients undergoing surgical procedures to help prevent nociceptive pathways from becoming overactive and causing either hyperalgesia or temporal summation, also known as wind-up pain.³ For patients with chronic pain, therapeutics that can be prescribed on an outpatient basis can help improve their comfort and overall quality of life.

References

1. Dooley S. Beyond the NSAIDS – a multimodal approach to chronic pain. Presented at: Directions in Veterinary Medicine; May 19-20, 2023; Miami, FL.
2. Funai Y, Pickering AE, Uta D, et al. Systemic dexmedetomidine augments inhibitory synaptic transmission in the superficial dorsal horn through activation of descending noradrenergic control: an in vivo patch-clamp analysis of analgesic mechanisms. Pain. 2014;155(3):617-628. doi:10.1016/j.pain.2013.12.018
3. Dydyk AM, Givler A. Central Pain Syndrome. StatPearls Publishing; 2023. Accessed June 20, 2023. https://www.ncbi.nlm.nih.gov/books/NBK553027/