A CB2 receptor agonist, A-836339, modulates wide dynamic range neuronal activity in neuropathic rats: Contributions of spinal and peripheral CB2 receptors

@article{McGaraughty2009ACR,
  title={A CB2 receptor agonist, A-836339, modulates wide dynamic range neuronal activity in neuropathic rats: Contributions of spinal and peripheral CB2 receptors},
  author={Steve P. McGaraughty and Katharine L. Chu and Michael J. Dart and Betty Bei Yao and Michael D. Meyer},
  journal={Neuroscience},
  year={2009},
  volume={158},
  pages={1652-1661}
}
We investigated the systemic and site-specific actions of a selective CB(2) receptor agonist, A-836339 on mechanically evoked (10 g von Frey hair) and spontaneous firing of spinal wide dynamic range (WDR) neurons in neuropathic (L5 and L6 ligations) and sham rats. Systemic administration of A-836339 (0.3-3 micromol/kg, i.v.) reduced both evoked and spontaneous WDR neuronal activity in neuropathic, but not sham rats. The effects in neuropathic rats were blocked by pre-administration of a CB(2… Expand
Antagonism of Supraspinal Histamine H3 Receptors Modulates Spinal Neuronal Activity in Neuropathic Rats
TLDR
Blockage of H3 receptors reduces spontaneous firing as well as the responses of spinal nociceptive neurons to mechanical stimulation, indicating that the descending modulatory system has an important role in the H3-related dampening of spinal neuronal activity. Expand
A mixed Ca2+ channel blocker, A-1264087, utilizes peripheral and spinal mechanisms to inhibit spinal nociceptive transmission in a rat model of neuropathic pain.
TLDR
Results indicate that A-1264087 selectively inhibited spinal nociceptive transmission in sensitized states through both peripheral and central mechanisms. Expand
TRPV1-related modulation of spinal neuronal activity and behavior in a rat model of osteoarthritic pain
TLDR
It is demonstrated that blockade of TRPV1 receptors modulates the firing of two important classes of spinal nociceptive neurons in a rat model of OA, and systemic administration of A-889425 reduced the elevated spontaneous firing of WDR neurons in OA rats but did not alter spontaneous firing in sham rats. Expand
Mechanistic insights into the analgesic efficacy of A-1264087, a novel neuronal Ca(2+) channel blocker that reduces nociception in rat preclinical pain models.
TLDR
The present results demonstrate that the neuronal Ca(2+) channel blocker A-1264087 exhibits broad-spectrum efficacy through engagement of nociceptive signaling pathways in preclinical pain models in the absence of effects on psychomotor and cognitive function. Expand
Spontaneous firing and evoked responses of spinal nociceptive neurons are attenuated by blockade of P2X3 and P2X2/3 receptors in inflamed rats
P2X3 and P2X2/3 receptors are selectively expressed on primary afferent nociceptors and have been implicated in modulating nociception in different models of pathological pain, including inflammatoryExpand
A mixed Ca 2 channel blocker , A-1264087 , utilizes peripheral and spinal mechanisms to inhibit spinal nociceptive transmission in a rat model of neuropathic pain
Xu J, Chu KL, Zhu CZ, Niforatos W, Swensen A, Searle X, Lee L, Jarvis MF, McGaraughty S. A mixed Ca channel blocker, A-1264087, utilizes peripheral and spinal mechanisms to inhibit spinal nociceptiveExpand
TRPA1 modulation of spontaneous and mechanically evoked firing of spinal neurons in uninjured, osteoarthritic, and inflamed rats
TLDR
Blockade of TRPA1 receptors disrupts transmission of high-intensity mechanical stimulation to the spinal cord in both uninjured and injured rats indicating that TRPA 1 receptors have an important role in noxious mechanosensation in both normal and pathological conditions. Expand
Tonic Modulation of Spinal Hyperexcitability by the Endocannabinoid Receptor System in a Rat Model of Osteoarthritis Pain
TLDR
The novel control of spinal cord neuronal responses by spinal cord CB2 receptors suggests that this receptor system may be an important target for the modulation of pain in OA. Expand
A selective α2B adrenoceptor agonist (A‐1262543) and duloxetine modulate nociceptive neurones in the medial prefrontal cortex, but not in the spinal cord of neuropathic rats
TLDR
A novel, potent and selective α2B receptor agonist is identified and studied to further explore this adrenoceptor subtype's contribution to pathological nociception. Expand
Metamizol, a non‐opioid analgesic, acts via endocannabinoids in the PAG‐RVM axis during inflammation in rats
TLDR
Results show that endocannabinoids and their CB1 receptor contribute at the LVL‐PAG to the antinociceptive effects of metamizol, and possibly other non‐opioid analgesics; and participate in the PAG‐derived activation of RVM descending antinOCiceptive influences. Expand
...
1
2
3
...

References

SHOWING 1-10 OF 53 REFERENCES
Systemic and site-specific effects of A-425619, a selective TRPV1 receptor antagonist, on wide dynamic range neurons in CFA-treated and uninjured rats.
TLDR
Noxious thermal stimulation triggers the transmission of TRPV1-related signals to spinal WDR neurons in both inflamed and uninjured animals, which may be the result of changes to the distribution/sensitization of peripheral TRpV1 receptors. Expand
Inhibitory effects of CB1 and CB2 receptor agonists on responses of DRG neurons and dorsal horn neurons in neuropathic rats
TLDR
At the level of the spinal cord, CB2 receptors have inhibitory effects in neuropathic, but not sham‐operated rats suggesting that spinal CB2 may be an important analgesic target. Expand
CB2 receptor‐mediated antihyperalgesia: possible direct involvement of neural mechanisms
TLDR
It is suggested that CB2 agonists may elicit their analgesic effect by acting not only at non‐neuronal peripheral sites but also at neural level, making CB2 an attractive target for chronic pain treatment. Expand
Contributions of central and peripheral TRPV1 receptors to mechanically evoked and spontaneous firing of spinal neurons in inflamed rats.
TLDR
The current data demonstrate that TRPV1 receptors have an enhanced role after an inflammatory injury, impacting both low-intensity mechanotransmission and possibly spontaneous pain. Expand
A Selective Nav1.8 Sodium Channel Blocker, A-803467 [5-(4-Chlorophenyl-N-(3,5-dimethoxyphenyl)furan-2-carboxamide], Attenuates Spinal Neuronal Activity in Neuropathic Rats
TLDR
The systemic effects of A-803467 in SNL rats were not altered by spinal transection or by systemic pretreatment with the transient receptor potential vanilloid type 1 (TRPV 1) receptor agonist, resiniferatoxin, at doses that impair the function of TRPV1-expressing fibers. Expand
P2X7-related modulation of pathological nociception in rats
TLDR
ATP, acting through the P2X7 receptor, exerts a wide-ranging influence on spinal neuronal activity following a chronic injury and is likely mediated through immuno-neural interactions that affect the release of endogenous cytokines. Expand
Effect of the cannabinoid CB1 receptor antagonist, SR141716, on nociceptive response and nerve demyelination in rodents with chronic constriction injury of the sciatic nerve
TLDR
The present findings suggest that SR141716 is effective not only in alleviating neuropathic pain but also in favouring the nerve myelin repair and consequently promote long‐lasting functional recovery. Expand
Cannabinoid CB2 receptor activation inhibits mechanically evoked responses of wide dynamic range dorsal horn neurons in naïve rats and in rat models of inflammatory and neuropathic pain
TLDR
It is demonstrated that activation of peripheral CB2 receptors attenuates both innocuous‐ and noxious‐evoked responses of WDR neurons in models of acute, inflammatory and neuropathic pain. Expand
Activation of cannabinoid CB2 receptors suppresses C-fiber responses and windup in spinal wide dynamic range neurons in the absence and presence of inflammation.
TLDR
It is demonstrated that activation of cannabinoid CB2 receptors is sufficient to suppress neuronal activity at central levels of processing in the spinal dorsal horn and this findings are consistent with the ability of AM1241 to normalize nociceptive thresholds and produce antinociception in inflammatory pain states. Expand
Activation of CB2 cannabinoid receptors by AM1241 inhibits experimental neuropathic pain: Pain inhibition by receptors not present in the CNS
  • M. Ibrahim, H. Deng, +8 authors T. Malan
  • Chemistry, Medicine
  • Proceedings of the National Academy of Sciences of the United States of America
  • 2003
TLDR
AM1241 dose-dependently reversed tactile and thermal hypersensitivity produced by ligation of the L5 and L6 spinal nerves in rats, demonstrating a mechanism leading to the inhibition of pain, one that targets receptors localized exclusively outside the CNS. Expand
...
1
2
3
4
5
...