Peripheral cannabinoids attenuate carcinoma-induced nociception in mice

Guerrero, André Vinicius Pires; Quang, Phuong N.; Dekker, Nusi P.; Jordan, Richard C.; Schmidt, Brian L.

doi:10.1016/j.neulet.2007.12.053

Cited by 41 publications

(32 citation statements)

References 43 publications

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“…In several studies, local administration of cannabinoids into inflamed tissue attenuated hyperalgesia and allodynia via peripheral CB 1 Rs, at doses that produced only minimal centrally mediated side effects [22,23]. Activation of peripheral CB 1 Rs could reduce mechanical activation of A-δ nociceptors from inflamed skin but not from non-inflamed skin [24] and attenuated hyperalgesia produced by thermal injury [25], nerve injury [26] and cancer [27,28]. Moreover, the crucial role of peripheral cannabinoid receptors in the antihyperalgesic actions of systemically administered cannabinoids was also demonstrated by experiments with conditional peripheral CB 1 R knockout mice.…”

Section: Cannabinoids For the Treatment Of Pain: Preclinical And Animmentioning

confidence: 99%

Is There Any Clinically Relevant Cannabinoid-Induced Analgesia?

Kraft¹

2012

Pharmacology

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Cannabis sativa is one of the oldest crops cultivated for the production of fibers and for medical and recreational purposes. Since the detection of specific cannabinoid receptors and their physiological ligands, the understanding of the cannabinoid signalling system has increased, leading to a recent resurgence of interest in its medicinal properties. In animal studies, cannabinoids exerted significant analgesic and antihyperalgesic effects, suggesting the usefulness of cannabinoids in pain conditions. However, in human experimental or clinical trials, no convincing reduction of acute pain was observed. In contrast, in chronic pain and (painful) spasticity, an increasing number of randomized, double-blind, placebo-controlled studies have shown some efficacy of cannabinoids. Besides pain, cannabinoids consistently improved mood, sleep and coping. Although cannabinoids are not first-line analgesics, they may be useful adjuvants for some special groups of patients.

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Section: Cannabinoids For the Treatment Of Pain: Preclinical And Animmentioning

confidence: 99%

Is There Any Clinically Relevant Cannabinoid-Induced Analgesia?

Kraft¹

2012

Pharmacology

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“…Studies in models of cancer pain have revealed differing effects on the expression of cannabinoid receptors within the CNS, with some groups reporting an upregulation of CB1 receptor in the L5 DRG in mice injected with squamous cell carcinoma into the hindpaw [46], while others studying models of bone cancer report no change in expression [48,60]. Despite these differences, administration of cannabinoid agonists produces robust analgesia in all models of cancer pain via activation of both CB1 [46,50,60] and CB2 receptors [46][47][48][49][50]. Interestingly, antinociceptive effects of both intrathecal and systemic administration of the CB2 receptor selective agonist AM1241 were abolished by intrathecal administration of the CB2 receptor antagonist SR144528, indicating a spinal site of action [48], and the effects of systemic AM1241 were blocked by naloxone [48], indicating a role of endogenous opioids, which warrants further investigation.…”

Section: Cb1 Receptor Modulation Of Pain Processing In Models Of Chromentioning

confidence: 99%

Dynamic changes to the endocannabinoid system in models of chronic pain

Sagar

Burston

Woodhams

et al. 2012

Phil. Trans. R. Soc. B

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The analgesic effects of cannabinoid ligands, mediated by CB1 receptors are well established. However, the side-effect profile of CB1 receptor ligands has necessitated the search for alternative cannabinoid-based approaches to analgesia. Herein, we review the current literature describing the impact of chronic pain states on the key components of the endocannabinoid receptor system, in terms of regionally restricted changes in receptor expression and levels of key metabolic enzymes that influence the local levels of the endocannabinoids. The evidence that spinal CB2 receptors have a novel role in the modulation of nociceptive processing in models of neuropathic pain, as well as in models of cancer pain and arthritis is discussed. Recent advances in our understanding of the spinal location of the key enzymes that regulate the levels of the endocannabinoid 2-AG are discussed alongside the outcomes of recent studies of the effects of inhibiting the catabolism of 2-AG in models of pain. The complexities of the enzymes capable of metabolizing both anandamide (AEA) and 2-AG have become increasingly apparent. More recently, it has come to light that some of the metabolites of AEA and 2-AG generated by cyclooxygenase-2, lipoxygenases and cytochrome P450 are biologically active and can either exacerbate or inhibit nociceptive signalling.

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“…Local administration of cannabinoids have also been shown to attenuate hyperalgesia produced by nerve injury (Fox et al 2001;, cutaneous heat injury (Johanek and Simone 2004), and cancer (Guerrero et al 2008;Potenzieri et al 2008) through activation of peripheral CB 1 receptors.…”

Section: Cannabinoid Attenuation Of Allodynia and Hyperalgesiamentioning

confidence: 99%

Cannabinoid Modulation of Cutaneous Aδ Nociceptors During Inflammation

Potenzieri

Brink

Pacharinsak

et al. 2008

Journal of Neurophysiology

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Previous studies have demonstrated that locally administered cannabinoids attenuate allodynia and hyperalgesia through activation of peripheral cannabinoid receptors (CB(1) and CB(2)). However, it is currently unknown if cannabinoids alter the response properties of nociceptors. In the present study, correlative behavioral and in vivo electrophysiological studies were conducted to determine if peripheral administration of the cannabinoid receptor agonists arachidonyl-2'-chloroethylamide (ACEA) or (R)-(+)-methanandamide (methAEA) could attenuate mechanical allodynia and hyperalgesia, and decrease mechanically evoked responses of Adelta nociceptors. Twenty-four hours after intraplantar injection of complete Freund's adjuvant (CFA), rats exhibited allodynia (decrease in paw withdrawal threshold) and hyperalgesia (increase in paw withdrawal frequency), which were attenuated by both ACEA and methAEA. The antinociceptive effects of these cannabinoids were blocked by co-administration with the CB(1) receptor antagonist N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophen yl)-4-methyl-1H-pyrazole-3-carboxamide (AM251) but not with the CB(2) receptor antagonist 6-iodo-2-methyl-1-[2-(4-morpholinyl)ethyl]-1H-indol-3-y l](4-methoxyphenyl)methanone (AM630). ACEA and methAEA did not produce antinociception under control, non-inflamed conditions 24 h after intraplantar injection of saline. In parallel studies, recordings were made from cutaneous Adelta nociceptors from inflamed or control, non-inflamed skin. Both ACEA and methAEA decreased responses evoked by mechanical stimulation of Adelta nociceptors from inflamed skin but not from non-inflamed skin, and this decrease was blocked by administration of the CB(1) receptor antagonist AM251. These results suggest that attenuation of mechanically evoked responses of Adelta nociceptors contributes to the behavioral antinociception produced by activation of peripheral CB(1) receptors during inflammation.

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Peripheral cannabinoids attenuate carcinoma-induced nociception in mice

Cited by 41 publications

References 43 publications

Is There Any Clinically Relevant Cannabinoid-Induced Analgesia?

Is There Any Clinically Relevant Cannabinoid-Induced Analgesia?

Dynamic changes to the endocannabinoid system in models of chronic pain

Cannabinoid Modulation of Cutaneous Aδ Nociceptors During Inflammation

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