Nerve damage and pathophysiological mechanisms of neuropathic pain in leprosy

1
Nerve damage and pathophysiological mechanisms of
neuropathic pain in leprosy

• role of vasculitis?
• ongoing inflammation in treated patients?
• small-fiber neuropathy?
• role of pro-inflammatory cytokines?
• role of microglia?

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Delayed vasculitic neuropathy

• Bowen JRC et al. J Neurol Neurosurg Psychiatry
  200068496-500
• case of a treated LL patient with a delayed
  vasculitic neuropathy precipitated by persisting
  M Leprae antigen

3
Nerve damage and pathophysiological mechanisms of
neuropathic pain in leprosy

• role of vasculitis?
• ongoing inflammation in treated patients?
• small-fiber neuropathy?
• role of pro-inflammatory cytokines?
• role of microglia?

4
Ongoing inflammation in leprosy

• 17 patients from Hyderabad, India (chronic
  neuropathic pain and treated leprosy)
• sural nerve biopsy 9/17 in 6 biopsies evidence
  of moderate ongoing inflammation, and in 5
  biopsies scanty intraneural acid-fast bacilli
• inflammation along nerve trunks is able to
  produce ectopic activity in nerves

5
Nerve damage and pathophysiological mechanisms of
neuropathic pain in leprosy

• role of vasculitis?
• ongoing inflammation in treated patients?
• small-fiber neuropathy?
• role of pro-inflammatory cytokines?
• role of microglia?

6
Lack of intraepidermal nerve fibers in leprosy
7
Intraepidermal nerve fibre density in healthy
controls and leprosy patients with pain
8
Nerve damage and pathophysiological mechanisms of
neuropathic pain in leprosy

• role of vasculitis?
• ongoing inflammation in treated patients?
• small-fiber neuropathy?
• role of pro-inflammatory cytokines?
• role of microglia?

9
Role of proinflammatory cytokines

• nerve injury always activates a local immune
  response
• inflammatory mediators enter the nerve from the
  blood stream
• individual ability to react with high or low
  production of pro-inflammatory cytokines upon
  nerve injury may be one reason for the degree of
  pain in peripheral neuropathies
• elevated serum levels of TNF and IL-1ß in leprosy
  patients with severe pain (treatment with
  thalidomide reduces TNF secretion and pain)

10
Nerve damage and pathophysiological mechanisms of
neuropathic pain in leprosy

• role of vasculitis?
• persistent inflammation in treated patients?
• small-fiber neuropathy?
• role of pro-inflammatory cytokines?
• role of microglia?

11
Role of microglia
12
Obrigado!