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Addiction Medicine: State of the Art 2003 Is There a Common Neural Substrate for Analgesia and Reward? PowerPoint Presentation
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Addiction Medicine: State of the Art 2003 Is There a Common Neural Substrate for Analgesia and Reward?. Robert W. Gear, D.D.S., Ph.D. Alternative Title. “Is it possible to develop an effective analgesic medication that does not have abuse potential?”. Reward Pathway. Opioids Amphetamine.

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Addiction Medicine: State of the Art 2003 Is There a Common Neural Substrate for Analgesia and Reward?


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slide1

Addiction Medicine: State of the Art 2003Is There a Common Neural Substrate for Analgesia and Reward?

Robert W. Gear, D.D.S., Ph.D.

alternative title
Alternative Title

“Is it possible to develop an effective analgesic medication that does not have abuse potential?”

slide4
Opioids

Amphetamine

Cocaine

Nicotine

All these substances

  • Release dopamine in nucleus accumbens
  • Have high abuse potential
  • Produce analgesia in humans or animals

Is nucleus accumbens important for analgesia?

pain induced analgesia
Pain-Induced Analgesia
  • Noxious Stimulus-Induced Antinociception
  • Induced by
    • Capsaicin (spicy component of chili peppers)
    • Thermal stimulation
measuring analgesia in the rat
Measuring Analgesia in the Rat

Trigeminal jaw-opening reflex (JOR)

  • Electrically stimulate mandibular incisor
  • Measure amplitude of digastric EMG
  • “Analgesia” = decrease in JOR
slide7

Pre-treatment

30 min post-treatment

Subcutaneous

morphine

10 mg/kg

mV

Intraplantar capsaicin

250 mg

mV

msec

msec

methods
Methods
  • To identify receptor subtypes mediating an effect, selective antagonists are administered.
  • To isolate an effect to a particular brain region, agents are microinjected (0.5 µl). The region of interest is targeted with a stereotaxic device.
  • We targeted nucleus accumbens and microinjected selective antagonists for opioid, dopamine, and nicotinic receptors.
nucleus accumbens experiments
Nucleus Accumbens Experiments
  • Antagonists for opioid receptors subtypes:
    • Non-selective: naloxone
    • Mu selective: CTOP
    • Delta selective: naltrindole
    • Kappa selective: nor-binaltorphimine
  • Acetylcholine nicotinic receptors: mecamylamine
  • Dopamine receptors: flupenthixol
opioid receptor subtypes
Opioid Receptor Subtypes

capsaicin alone

+ kappa

+ delta

+ mu

recap
Noxious stimuli can produce analgesia equivalent to high dose morphine

This analgesic effect is mediated in nucleus accumbens

Opioid, dopamine and nicotinic receptors are all involved

Recap
summary intra accumbens receptors
Opioids

Cocaine, amphetamine

Nicotine

Noxious stimulation

Mu, delta, kappa receptors

Dopamine receptors

Acetylcholine nicotinic rec.

Mu, delta, dopamine, nicotine receptors

Summary: Intra-accumbens Receptors
summary intra accumbens dopamine
Summary: Intra-accumbens Dopamine

Dopamine in nucleus accumbens increases in response to administration of

  • Opioids
  • Cocaine/amphetamine
  • Nicotine
  • Noxious stimulation
conclusion
Conclusion

Nucleus accumbens appears to be a neural substrate for both behavioral reinforcement and analgesia.

so

It may not be possible to separate analgesic effects from abuse potential.

but an intriguing unanswered question remains:

Can noxious stimuli be rewarding?

slide20

Jon Levine

Brian Schmidt

Claudia Tambeli

Lei Luo