Neuropathic pain treated by amitriptyline in two cats

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Neuropathic pain treated by amitriptyline in two
cats
Merial Pain Management Symposium April 22-24,
2009 Tenerife, Spain

• Stephan Mahler DVM, PhD
• Karine Ménier DVM, PhD

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Introduction

• Animal pain and suffering are clinically
  important conditions
• Unrelieved pain does not provide any benefit in
  animals
• Surgical pain, osteoarthritis, traumatic and
  medical pain
• There has been little discussion on neuropathic
  pain

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Case 1

• 4 yo neutered DSH male cat
• Sudden limb paralysis
• Hypertrophic cardiomyopathy
• Benazepril 2,5mg
• Persistent lameness and pain
• Decreased appetite, weight loss, avoiding any
  interaction

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Case 1

• 3 weeks NSAIDs, opioids
• Amitriptyline 3mg/kg SID
• Improvement after 3 days
• Normal exploratory and social behaviour after 3
  weeks
• No side effect, no recurrence (follow-up of 8
  months)

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Case 2

• 1 yo neutered DSH male cat
• Self mutilation at the tail
• Started 3-4 months previously
• Decreased appetite, weight loss
• Increasingly isolated, showed aggressive
  behaviours
• Started crises with increased
  frequency/violence
• Described as a craze attack
• Running around the apartment
• Meow, hiss, growl, muscular tremor
• Attack his tail, scratching and biting it

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Case 2

• Scars and wounds over the entire length of the
  tail
• Hair had been pulled out or was broken
• Palpation allodynia at the level of sacral
  area/tail
• Radiographs and ultrasound examination
• Treatment
• Meloxicam - 0,1mg/kg SID, 1 week
• Amitriptyline - 5mg/kg SID, 1 month
• - 5mg/kg every other day for 2 weeks
• - 2,5mg/kg every other day for 2 weeks

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Case 2

• Improvement after 2-3 days of treatment
• Calmer and normal behaviour after 10 days
• Self-mutilation reappeared at the end of
  treatment
• Treatment (Amitriptyline) was prolonged for 1
  month
• No side effect, no recurrence (follow-up of 2
  years)

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Discussion

• Definiton of neuropathic pain (IASP)
• Pain initiated or caused by a primary lesion or
  dysfunction in the nervous system
• Neuropathic pain ? acute pain

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Discussion

• The development of neuropathic pain
• (Dworkin et al. Arch Neurol 2003)
• Injury/disease that damages the axon
• Central sensitization (Wind-up)
• Sensory-Sympathetic coupling

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Discussion

• The development of neuropathic pain
• Injury/disease that damages the axon
• Ectopic firing tends to occur (tingling,
  prickling, burning)
• Injury/disruption allows electrical and chemical
  cross-excitation between Aß fibers and C-fibers
  (allodynia)

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Discussion

• The development of neuropathic pain
• Central sensitization (Wind-up)
• Release of glutamate in the synaptic cleft
• Activation of NMDA on the post-synaptic membrane.
• Increase excitability of the neurons
• Increased levels of protein production (COX-2)

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Discussion

• The development of neuropathic pain
• Sensory-Sympathetic coupling
• Normally sympathetic activity does not cause pain
• However, nerve injury can induce noradrenergic
  supersensitivity
• Contribute to stimulus-
• independent neuropathic pain

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Discussion

• Origin of the pain in case1
• Spinal cord ischemia caused by the embolism
• Ischemia could have lead to a spinal cord lesion
• Development of a neuroma
• Origin of the pain in case2
• Probable trauma of the tail
• Peripheral deafferentation lesion

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Discussion

• Diagnosis of neuropathic pain (Hayes et al. Acute
  Pain 2002)
• 1. History consistent with nerve injury
• 2. Pain within but not necessarily confined to an
  area of sensory deficit
• 3. Pain in the absence of ongoing tissue damage
• 4. Character of pain burning, pulsing, shooting,
  or stabbing
• 5. Paroxysmal or spontaneous pain
• 6. Associated dysesthesias
• 7. Allodynia, secondary hyperalgesia, or
  hyperpathia
• 8. Associated autonomic features

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Discussion

• Diagnosis of neuropathic pain in animals
• Absence of verbal communication
• Not so well-known/unreported primary conditions
• Neuropathic pain is a chronic pain
• Decreased appetite
• Weight loss
• Decreased social interaction
• Aggressive behaviours

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Discussion

• Diagnosis of neuropathic pain in case1
• Appearance of a chronic pain syndrome
• Several weeks after a clearly identified initial
  neurologic lesion
• Diagnosis of neuropathic pain in case2
• Appearance of a chronic syndrome
• Paroxysmal, dazzling pain ( electric shocks)
• Allodynia

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Discussion
Treatment of neuropathic pain

• Decrease spontaneous neuronal activity
• Inhibit ion channel
• Lidocaine (Valverde et al. Vet Anaesth Anal 2004)
• Gabapentin (Wallace, Curr Pain Headacke Rep 2001)
• Pregabalin (Blommel, Am J Health Syst Pharm 2007)
• Tricyclic antidepressants

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Discussion
Treatment of neuropathic pain

• Inhibiting the neuronal reuptake of 5HT and NE
• Tricyclic antidepressants (Wallace, Curr Pain
  Headache Rep 2001)
• Tramadol (Arbaiza, Clin Drug Investig 2007)

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Discussion
Treatment of neuropathic pain

• Decreasing the glutamate receptor activation NMDA
• Tricyclic antidepressants (Wallace, Curr Pain
  Headache Rep 2001)
• Ketamine (Wagner et al. JAVMA 2002, Sarrau et
  al. JSAP 2007)
• Amantadine (Lascelles et al. J Vet Intern Med
  2008)

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Discussion
Amitriptyline in neuropathic pain

• Effective analgesics for neuropathic conditions
  (Chew et al., JAVMA 1998)
• Analgesic effects occur at lower doses (side
  effects?)
• Clinical improvement occurs within 48h (Mathews,
  Vet Clin Small Anim 2008)
• Administred orally every 24 h

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Conclusion

• Neuropathic pain is a clinical syndrome of pain
• It serves no beneficial purpose
• Complex and incompletely understood.
• Creative, mechanism-specific, multimodal
  treatment
• Amitriptyline is a good first-choice option in
  cat