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A critical period in the supraspinal control of pain: opioid-dependent changes in brainstem rostroventral medulla

Gareth J Hathway1, David Vega-Avelaira, Maria Fitzgerald

  • 1UCL Neuroscience, Physiology and Pharmacology, University College London, London, UK School of Biomedical Sciences, The University of Nottingham, Nottingham, UK.

Pain
|February 14, 2012
PubMed

Insights

Pain control pathways in young rats switch from facilitation to inhibition. This developmental switch in descending brainstem control is mediated by micro-opioid receptors in the rostroventral medulla (RVM) during a critical periadolescent period.

Area of Science:

  • Neuroscience
  • Developmental Biology
  • Pain Research

Background:

  • Descending brainstem pathways modulate spinal nociceptive reflexes.
  • Developmental changes in pain modulation are not fully understood.
  • Micro-opioid receptors in the rostroventral medulla (RVM) play a role in pain control.

Purpose of the Study:

  • To investigate the role of micro-opioid receptors in the RVM during the developmental switch of descending pain control.
  • To determine the critical developmental period for the transition from pain facilitation to inhibition.
  • To elucidate the involvement of central opioid networks in this developmental process.

Main Methods:

  • Microinjections of micro-opioid receptor agonists (DAMGO) and antagonists (CTOP) into the RVM of adult and preadolescent rats.
  • Administration of naloxone hydrochloride to block tonic opioidergic activity during specific developmental windows.
  • Chronic morphine administration to enhance opioidergic activity at different postnatal ages.
  • Measurement of hindlimb mechanical nociceptive reflex electromyographic activity.

Main Results:

  • Microinjections of DAMGO facilitated nociceptive reflexes in preadolescent rats but inhibited them in adults.
  • Blockade of tonic opioidergic activity from postnatal day 21 to 28 prevented the normal development of inhibitory control.
  • Enhancing opioidergic activity earlier (postnatal day 7-14) accelerated the development of inhibitory control.
  • RVM microinjections of delta-opioid or GABA(A) receptor agonists caused reflex depression at both ages.

Conclusions:

  • Descending facilitation of spinal nociception in young animals is mediated by micro-opioid receptor pathways in the RVM.
  • The developmental transition from RVM descending facilitation to inhibition of pain is determined by activity in central opioid networks.
  • A critical periadolescent period exists for the development of descending inhibitory pain control.

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