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Δ9-Tetrahydrocannabinol and Cannabinol Activate Capsaicin-Sensitive Sensory Nerves via a CB1 and CB2 Cannabinoid Receptor-Independent Mechanism

Zygmunt, Peter M. LU orcid ; Andersson, David A. LU and Högestätt, Edward D. LU (2002) In The Journal of Neuroscience 22(11). p.4720-4727
Abstract

Although Δ9-tetrahydrocannabinol (THC) produces analgesia, its effects on nociceptive primary afferents are unknown. These neurons participate not only in pain signaling but also in the local response to tissue injury. Here, we show that THC and cannabinol induce a CB1/CB 2 cannabinoid receptor-independent release of calcitonin gene-related peptide from capsaicin-sensitive perivascular sensory nerves. Other psychotropic cannabinoids cannot mimic this action. The vanilloid receptor antagonist ruthenium red abolishes the responses to THC and cannabinol. However, the effect of THC on sensory nerves is intact in vanilloid receptor subtype 1 gene knock-out mice. The THC response depends on extracellular... (More)

Although Δ9-tetrahydrocannabinol (THC) produces analgesia, its effects on nociceptive primary afferents are unknown. These neurons participate not only in pain signaling but also in the local response to tissue injury. Here, we show that THC and cannabinol induce a CB1/CB 2 cannabinoid receptor-independent release of calcitonin gene-related peptide from capsaicin-sensitive perivascular sensory nerves. Other psychotropic cannabinoids cannot mimic this action. The vanilloid receptor antagonist ruthenium red abolishes the responses to THC and cannabinol. However, the effect of THC on sensory nerves is intact in vanilloid receptor subtype 1 gene knock-out mice. The THC response depends on extracellular calcium but does not involve known voltage-operated calcium channels, glutamate receptors, or protein kinases A and C. These results may indicate the presence of a novel cannabinoid receptor/ion channel in the pain pathway.

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author
; and
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Calcitonin gene-related peptide, Cannabinoids, Cannabinol, Cannabis, Capsaicin, Nociceptors, Pain, Receptors, sensory, Tetrahydrocannabinol
in
The Journal of Neuroscience
volume
22
issue
11
pages
8 pages
publisher
Society for Neuroscience
external identifiers
  • pmid:12040079
  • scopus:0036617759
ISSN
0270-6474
DOI
10.1523/JNEUROSCI.22-11-04720.2002
language
English
LU publication?
no
id
710cd5a7-4970-44ca-8a33-63e0284dcf08
date added to LUP
2019-05-30 16:01:38
date last changed
2024-03-03 12:20:26
@article{710cd5a7-4970-44ca-8a33-63e0284dcf08,
  abstract     = {{<p>Although Δ<sup>9</sup>-tetrahydrocannabinol (THC) produces analgesia, its effects on nociceptive primary afferents are unknown. These neurons participate not only in pain signaling but also in the local response to tissue injury. Here, we show that THC and cannabinol induce a CB<sub>1</sub>/CB <sub>2</sub> cannabinoid receptor-independent release of calcitonin gene-related peptide from capsaicin-sensitive perivascular sensory nerves. Other psychotropic cannabinoids cannot mimic this action. The vanilloid receptor antagonist ruthenium red abolishes the responses to THC and cannabinol. However, the effect of THC on sensory nerves is intact in vanilloid receptor subtype 1 gene knock-out mice. The THC response depends on extracellular calcium but does not involve known voltage-operated calcium channels, glutamate receptors, or protein kinases A and C. These results may indicate the presence of a novel cannabinoid receptor/ion channel in the pain pathway.</p>}},
  author       = {{Zygmunt, Peter M. and Andersson, David A. and Högestätt, Edward D.}},
  issn         = {{0270-6474}},
  keywords     = {{Calcitonin gene-related peptide; Cannabinoids; Cannabinol; Cannabis; Capsaicin; Nociceptors; Pain; Receptors, sensory; Tetrahydrocannabinol}},
  language     = {{eng}},
  month        = {{06}},
  number       = {{11}},
  pages        = {{4720--4727}},
  publisher    = {{Society for Neuroscience}},
  series       = {{The Journal of Neuroscience}},
  title        = {{Δ9-Tetrahydrocannabinol and Cannabinol Activate Capsaicin-Sensitive Sensory Nerves via a CB1 and CB2 Cannabinoid Receptor-Independent Mechanism}},
  url          = {{http://dx.doi.org/10.1523/JNEUROSCI.22-11-04720.2002}},
  doi          = {{10.1523/JNEUROSCI.22-11-04720.2002}},
  volume       = {{22}},
  year         = {{2002}},
}