Opiate antagonists in the treatment of chronic pain

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Opiate antagonists in the treatment of chronic
pain

• Dmitry M. Arbuck, MD
• Assistant Professor of Psychiatry and Medicine,
  Indiana University School of Medicine

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Tolerance to opioids

• May be prevented by non-competitive NMDA receptor
  antagonist MK-801 (1)
• The same is true about competitive NMDA receptor
  antagonists (ketamine, dextromethorphan)
  prevention and reversal of tolerance. (2)
• Tx doses of opiates shorten DRG action potential.
  Ultra low doses on another hand do the opposite.
  Ultra low doses of naloxone and naltrexone block
  this effect (3)
• 1.Trujillo K.A. and Akil H. Science
  199125185-87
• 2. Elliot K, N Minami et al., Pain
  1994(56)69-75
• 3. CrainSM, K-F Shen Pain 2000121-131

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Excitation vs. inhibition

• Excitatory effects of opioids have been observed
  with opioids with affinities for different
  receptor subtypes (mu, delta, kappa) (1)
• Inhibitory effects occur at the same time
  (bimodal effect) (2)
• Ultra-low doses of opioid antagonists result in
  blockade of excitatory effects (hyperalgesia) and
  potentiate inhibitory effects (analgesia) (3)
• 1. Cruciani RA, Pasternak GW Abstract. Soc.
  Neuros. 1999 (25)1478
• 2. Crain SM Shen K-F Trends in Parmacol. Sci
  19901177-81
• 3. Cruciani RA, Arbuck DM Jor. Of Pain and Syndr.
  Manag. 2003256491-494

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Cruciani RA, Arbuck DM ad al. Journal Of Pain and
Syndr. Manag. 2003256491-494
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OPIATE RECEPTOR

• Increase in tolerance Pain control
• Agitation Sedation
• Hallucinations Mental slowing
• Irritability Fatigue
• Insomnia Weight gain
• Edema Constipation
• Muscle twitching Weakness
• Sweating Urinary retention
• Rash Dry skin
• Nausea Dry mouth
• HA Respiratory depr.

Excitatory
Inhibitory
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Case report

• 61 y.o. male with painful diabetic peripheral
  neuropathy
• 9/10 burning, constant pain in hands and half way
  up the shins on Methadone 240mg/d and oxycodone
  10mg QID prn
• Naltrexone 11mu 1cc BID
• Pain 3/10 chronic nausea stopped, methadone
  decreased to 200mg /d

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Case report

• 58 y.o. female with R leg RSD.
• 4 low leg edema on any narcotic with repeated
  cellulitis and multiple admissions for IV
  antibiotics
• Naltrexone 11mu 3cc po BID
• Complete resolution of edema on same dose of
  narcotic medication (Kadian)
• Naltrexone discontinuation trial ended up in
  another cellulitis hospitalization
• Reinstitution of naltrexone controls edema for
  over 1.5 years

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Case report

• 42 y.o. male with CLBP controlled with Oxycontin.
  Severe profuse sweating not responding to Hytrin,
  Atarax, Doxepine, DrySol, etc
• Naltrexone 11 mu 2cc po BID
• Minimal controlled sweating.
• Repeated discontinuation trials cause return of
  disabling sweating

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Two patients types

• A. Pts. with more sensitivity to excitation on
  narcotics more excitatory AE, faster tolerance
  development, drug seeking, less pain control, may
  have pain increase
• B. Pts. with more sensitivity to inhibition
  better pain control, slower development of
  tolerance, but severe sedation and other
  inhibitory AE
• A B Pts. are on the continuum from A to B
  with an infinite variations of individual
  sensitivity to narcotics in general and to
  individual medications in particular

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