Antinociceptive effect of intrathecal cannabinoid receptor agonist WIN 55,212-2 in a rat bone tumor pain model

Cui, Jinghua; Kim, Woong Mo; Lee, Hyung Gon; Kim, Ye Ok; Kim, Chang Mo; Yoon, Myung Ha

doi:10.1016/j.neulet.2010.12.052

Cited by 26 publications

(20 citation statements)

References 31 publications

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“…On the other hand, it has been reported that several neurochemicals appear to be involved in bone tumor pain in the spinal cord [3,4]. Moreover, animal models of bone tumor pain have been developed [8,20]. These advances may accelerate the study of bone tumor pain.…”

Section: Discussionmentioning

confidence: 99%

“…Syngeneic MRMT-1 rat mammary gland carcinoma cells were cultured in media and then media or 1 × 10 5 tumor cells were injected into the medullary cavity of the right tibia to induce bone tumor according to a previously described method [8]. Under sevoflurane anesthesia, a 1/4 FG 0.5-mm round dental bur was used for intramedullary canalling.…”

Section: Methodsmentioning

confidence: 99%

“…Thus, we did experiments at this time [8]. The rats were placed the plastic cages and allowed to acclimate for a period of 20-30 min for the behavioral experiment.…”

Section: Methodsmentioning

confidence: 99%

“…Previous studies have shown that spinal CB receptor agonists decreased carrageenan-induced thermal hyperalgesia and bone cancer pain [6,7]. Recently, we demonstrated that intrathecal WIN 55,212-2, a CB receptor agonist, reduced bone-tumor-related pain behavior and that both CB1 and CB2 receptor antagonists reversed the effect at the spinal level [8]. …”

Section: Introductionmentioning

confidence: 92%

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Pharmacology of Cannabinoid Receptor Agonists and a Cyclooxygenase-2 Inhibitor in Rat Bone Tumor Pain

Cui

Yoon

2013

Pharmacology

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We evaluated the pharmacology of spinal selective cannabinoid (CB) receptor agonists and a cyclooxygenase-2 (COX-2) inhibitor on bone tumor pain. MRMT-1 tumor cells were injected into the tibia of female Sprague-Dawley rats. MRMT-1 tumor cells produced a bone tumor confirmed by radiologic and histological findings. Intrathecal CB1 (ACEA) and CB2 receptor (AM 1241) agonists and a COX-2 inhibitor (DuP 697) dose-dependently increased the withdrawal threshold. The calculated ED₅₀ (nmol/l) values for ACEA, AM 1241 and DuP 697 were 0.007, 2.3 and 76.1, respectively. Reverse transcriptase polymerase chain reaction and Western blot showed that COX-2 mRNA and protein, but not CB1 or CB2 receptor, were increased in the spinal cords of rats with bone tumors. Spinal CB1 receptor and CB2 receptor agonists and COX-2 inhibitor may be useful in the management of bone tumor pain. Furthermore, CB2 receptor agonist may be more potent than CB1 receptor agonist and COX-2 inhibitor.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

“…Thus, we did experiments at this time [8]. The rats were placed the plastic cages and allowed to acclimate for a period of 20-30 min for the behavioral experiment.…”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 92%

See 2 more Smart Citations

Pharmacology of Cannabinoid Receptor Agonists and a Cyclooxygenase-2 Inhibitor in Rat Bone Tumor Pain

Cui

Yoon

2013

Pharmacology

Self Cite

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“…Spinally, CB1 receptors are expressed in neurons while CB2 receptors are expressed on microglia, where the CB1 agonists reduce excitatory transmitter release and CB2 receptors attenuate microglial activation [359,360]. Intrathecal delivery of both CB1 and CB2 preferring ligands reduced facilitated states such as the formalin model, hyperpathia in neuropathy models and in tumor bone pain in rodents [361][362][363]. As many of these ligands have very high cLogPs, appropriate formulation in spinally compatible vehicles is an important consideration in their development for spinal use.…”

Section: Cannabinoidsmentioning

confidence: 99%

Current and Future Issues in the development of spinal agents for the management of pain

Yaksh¹,

Fisher²,

Hockman³

et al. 2016

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Targeting analgesic drugs for spinal delivery reflects the fact that while the conscious experience of pain is mediated supraspinally, input initiated by high intensity stimuli, tissue injury and/or nerve injury is encoded at the level of the spinal dorsal horn and this output informs the brain as to the peripheral environment. This encoding process is subject to strong upregulation resulting in hyperesthetic states and downregulation reducing the ongoing processing of nociceptive stimuli reversing the hyperesthesia and pain processing. The present review addresses the biology of spinal nociceptive processing as relevant to the effects of intrathecally-delivered drugs in altering pain processing following acute stimulation, tissue inflammation/injury and nerve injury. The review covers i) the major classes of spinal agents currently employed as intrathecal analgesics (opioid agonists, alpha 2 agonists; sodium channel blockers; calcium channel blockers; NMDA blockers; GABA A/B agonists; COX inhibitors; ii) ongoing developments in the pharmacology of spinal therapeutics focusing on less studied agents/targets (cholinesterase inhibition; Adenosine agonists; iii) novel intrathecal targeting methodologies including gene-based approaches (viral vectors, plasmids, interfering RNAs); antisense, and toxins (botulinum toxins; resniferatoxin, substance P Saporin); and iv) issues relevant to intrathecal drug delivery (neuraxial drug distribution), infusate delivery profile, drug dosing, formulation and principals involved in the preclinical evaluation of intrathecal drug safety.Keywords: Adenovirus transfection, dorsal horn, neurotoxins, pain pathways, spinal drug delivery, spinal analgesics, toxicity. RATIONALETargeting analgesic drugs for direct spinal delivery reflects the fact that while the conscious experience of pain is mediated supraspinally, input initiated by high intensity stimuli, tissue injury and/or nerve injury is encoded at the level of the spinal dorsal horn. Thus, high intensity (e.g., nociceptive) stimulation activates populations of small primary afferents, generating an intensity-dependent increase in activity of second order dorsal horn projection neurons. This excitation is transmitted through spinofugal projection pathways to higher centers, such as the somatosensory thalamus -somatosensory cortex, and to the medial thalamus -limbic cortices that are respectively believed to underlie the sensory-discriminative and affectivemotivational components of the pain experience [1-3]. The dorsal horn encoding process reflects a remarkable plasticity wherein the input-output function of the spinal dorsal horn is subject to pronounced regulation by local neuronal and nonneuronal circuits as well as supraspinal (bulbospinal) input. Thus, following tissue or nerve injury there is an enhanced neuronal response to moderate or low intensity stimuli, e.g., *Address correspondence to this author at the University of California, San Diego, Anesthesia Research Lab 0818, 9500 Gilman Dr. LaJolla, CA 92093, USA; ...

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Cancer pain: news about animal models

Lefèvre

Voisin

2013

Douleur analg

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Antinociceptive effect of intrathecal cannabinoid receptor agonist WIN 55,212-2 in a rat bone tumor pain model

Cited by 26 publications

References 31 publications

Pharmacology of Cannabinoid Receptor Agonists and a Cyclooxygenase-2 Inhibitor in Rat Bone Tumor Pain

Pharmacology of Cannabinoid Receptor Agonists and a Cyclooxygenase-2 Inhibitor in Rat Bone Tumor Pain

Current and Future Issues in the development of spinal agents for the management of pain

Cancer pain: news about animal models

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