Are the persistent effects of “gate control” stimulation on nociception a form of generalization of habituation that is endocannabinoid-dependent?

Alex Hanson, Brian D Burrell

Research output: Contribution to journalArticle

Abstract

Repetitive activation of non-nociceptive afferents is known to attenuate nociceptive signaling. However, the functional details of how this modulatory process operates are not understood and this has been a barrier in using such stimuli to effectively treat chronic pain. The present study tests the hypothesis that the ability of repeated non-nociceptive stimuli to reduce nociception is a form of generalized habituation from the non-nociceptive stimulus-response pathway to the nociceptive pathway. Habituation training, using non-nociceptive mechanosensory stimuli, did reduce responses to nociceptive thermal stimulation. This generalization of habituation to nociceptive stimuli required endocannabinoid-mediated neuromodulation, although disrupting of endocannabinoid signaling did not affect “direct” habituation of to the non-nociceptive stimulus. Surprisingly, the reduced response to nociceptive stimuli following habituation training was very long-lasting (3–8 days). This long-term habituation required endocannabinoid signaling during the training/acquisition phase, but endocannabinoids were not required for post-training retention phase. The implications of these results are that applying principles of habituation learning could potentially improve anti-nociceptive therapies utilizing repeated non-nociceptive stimulation such as transcutaneous nerve stimulation (TENS), spinal cord stimulation (SCS), or electro-acupuncture.

Original languageEnglish (US)
Pages (from-to)361-370
Number of pages10
JournalNeurobiology of Learning and Memory
Volume155
DOIs
StatePublished - Nov 1 2018

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Endocannabinoids
Nociception
Spinal Cord Stimulation
Transcutaneous Electric Nerve Stimulation
Aptitude
Acupuncture
Chronic Pain
Hot Temperature
Learning
Therapeutics

Keywords

  • Endocannabinoid
  • Habituation
  • Leech
  • Nociception
  • Pain
  • TRPV

ASJC Scopus subject areas

  • Experimental and Cognitive Psychology
  • Cognitive Neuroscience
  • Behavioral Neuroscience

Cite this

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title = "Are the persistent effects of “gate control” stimulation on nociception a form of generalization of habituation that is endocannabinoid-dependent?",
abstract = "Repetitive activation of non-nociceptive afferents is known to attenuate nociceptive signaling. However, the functional details of how this modulatory process operates are not understood and this has been a barrier in using such stimuli to effectively treat chronic pain. The present study tests the hypothesis that the ability of repeated non-nociceptive stimuli to reduce nociception is a form of generalized habituation from the non-nociceptive stimulus-response pathway to the nociceptive pathway. Habituation training, using non-nociceptive mechanosensory stimuli, did reduce responses to nociceptive thermal stimulation. This generalization of habituation to nociceptive stimuli required endocannabinoid-mediated neuromodulation, although disrupting of endocannabinoid signaling did not affect “direct” habituation of to the non-nociceptive stimulus. Surprisingly, the reduced response to nociceptive stimuli following habituation training was very long-lasting (3–8 days). This long-term habituation required endocannabinoid signaling during the training/acquisition phase, but endocannabinoids were not required for post-training retention phase. The implications of these results are that applying principles of habituation learning could potentially improve anti-nociceptive therapies utilizing repeated non-nociceptive stimulation such as transcutaneous nerve stimulation (TENS), spinal cord stimulation (SCS), or electro-acupuncture.",
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N2 - Repetitive activation of non-nociceptive afferents is known to attenuate nociceptive signaling. However, the functional details of how this modulatory process operates are not understood and this has been a barrier in using such stimuli to effectively treat chronic pain. The present study tests the hypothesis that the ability of repeated non-nociceptive stimuli to reduce nociception is a form of generalized habituation from the non-nociceptive stimulus-response pathway to the nociceptive pathway. Habituation training, using non-nociceptive mechanosensory stimuli, did reduce responses to nociceptive thermal stimulation. This generalization of habituation to nociceptive stimuli required endocannabinoid-mediated neuromodulation, although disrupting of endocannabinoid signaling did not affect “direct” habituation of to the non-nociceptive stimulus. Surprisingly, the reduced response to nociceptive stimuli following habituation training was very long-lasting (3–8 days). This long-term habituation required endocannabinoid signaling during the training/acquisition phase, but endocannabinoids were not required for post-training retention phase. The implications of these results are that applying principles of habituation learning could potentially improve anti-nociceptive therapies utilizing repeated non-nociceptive stimulation such as transcutaneous nerve stimulation (TENS), spinal cord stimulation (SCS), or electro-acupuncture.

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