Cannabinoids in anaesthesia and pain therapy

Azad, Shahnaz Christina; Rammes, Gerhard

doi:10.1097/01.aco.0000174959.05383.9c

Cited by 15 publications

(11 citation statements)

References 30 publications

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“…The most important clinically applied cannabinoid is ⌬ 9 -THC. Among others, this substance is known to have analgesic, sedative, and mood improving properties, which are useful in cancer patients suffering from pain and fear (Azad and Rammes 2005). In the present study we found that ⌬ 9 -THC significantly reduces LTD induction.…”

Section: +supporting

confidence: 66%

Activation of CB1 specifically located on GABAergic interneurons inhibits LTD in the lateral amygdala

Azad¹,

Kurz²,

Marsicano³

et al. 2008

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Previously, we found that in the lateral amygdala (LA) of the mouse, WIN55,212-2 decreases both glutamatergic and GABAergic synaptic transmission via activation of the cannabinoid receptor type 1 (CB1), yet produces an overall reduction of neuronal excitability. This suggests that the effects on excitatory transmission override those on inhibitory transmission. Here we show that CB1 activation by WIN55,212-2 and ⌬ 9-THC inhibits long-term depression (LTD) of basal synaptic transmission in the LA, induced by low-frequency stimulation (LFS; 900 pulses/1 Hz). The CB1 agonist WIN55,212-2 blocked LTD via G i/o proteins, activation of inwardly rectifying K + channels (K ir s), inhibition of the adenylate cyclase-protein kinase A (PKA) pathway, and PKA-dependent inhibition of voltage-gated N-type Ca 2+ channels (N-type VGCCs). Interestingly, WIN55,212-2 effects on LTD were abolished in CB1 knock-out mice (CB1-KO), and in conditional mutants lacking CB1 expression only in GABAergic interneurons, but were still present in mutants lacking CB1 in principal forebrain neurons. LTD induction per se was unaffected by the CB1 antagonist SR141716A and was normally expressed in CB1-KO as well as in both conditional CB1 mutants. Our data demonstrate that activation of CB1 specifically located on GABAergic interneurons inhibits LTD in the LA. These findings suggest that CB1 expressed on either glutamatergic or GABAergic neurons play a differential role in the control of synaptic transmission and plasticity.The amygdala integrates inputs from various brain regions such as the hippocampus, the prefrontal cortex, and the thalamus, providing a common output and playing an important role in fear memory, triggered reminders of past aversive experiences, and also pain processing (Le Doux 2000;Davis and Whalen 2001;Neugebauer et al. 2004). We previously showed that endocannabinoids released in the amygdala are important for the extinction of aversive memory (Marsicano et al. 2002). Most behavioral effects of exogenously applied cannabinoids (Manning et al. 2001;Pertwee 2001) . In the amygdala, electrophysiological findings also speak in favor of both glutamatergic and GABAergic localization of CB1 receptors. In the lateral amygdala (LA), the agonist WIN55,212-2 reduced isolated glutamatergic and GABAergic currents ) via activation of CB1 receptors. Although it may be assumed that these effects may compensate each other, the application of WIN55,212-2 induced an overall decrease of basal synaptic transmission. This indicates that in the LA, cannabinoid-induced modulation of neuronal activity is mainly determined by CB1 receptors located on excitatory pyramidal neurons.Earlier studies showed that CB1 receptor activation also modulates synaptic plasticity, since cannabinoids influence long-term potentiation and long-term depression (LTD) of synaptic transmission in different brain regions (Misner and Sullivan 1999;Auclair et al. 2000). However, little is known about the mechanisms and the neuronal sites where these CB1-mediated effects are e...

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Section: +supporting

confidence: 66%

Activation of CB1 specifically located on GABAergic interneurons inhibits LTD in the lateral amygdala

Azad¹,

Kurz²,

Marsicano³

et al. 2008

Learn. Mem.

Self Cite

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“…Nevertheless, preclinical and clinical data suggest that lower doses of cannabinoids may be effective for the treatment of allodynia and hyperalgesia in neuropathic pain. It seems that cannabinoids should be applied as low-dose co-analgesics to inhibit neuroplasticity and central sensitization rather than as analgesics in acute pain [1] . It is concluded that the stimulation of both CB-1 and CB-2 receptors inhibited transmission of pain stimuli in STZ-induced diabetes.…”

Section: Discussionmentioning

confidence: 99%

“…

development of new experimental methods during the past several decades has made it possible to understand the mechanisms of cannabinoid action [1,2] . The existence of endogenous ligands for cannabinoid receptors, e.g.

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mentioning

confidence: 99%

Effect of Cannabinoid Receptor Agonists on Streptozotocin-Induced Hyperalgesia in Diabetic Neuropathy

Bujalska

2008

Pharmacology

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The effect of CB-1 and CB-2 receptor agonists, as well as an influence of a non-selective inhibitor of nitric oxide synthase (NOS), L-NOArg, and an inhibitor acting preferentially on cyclooxygenase-1 (COX-1), indomethacin, on the action of cannabinoid receptor agonists in a streptozotocin (STZ)-induced neuropathic model was investigated. When administered alone, a non-selective cannabinoid receptor agonist, WIN 55,212-2, a potentially selective CB-1 cannabinoid receptor agonist, Met-F-AEA, and a selective CB-2 cannabinoid receptor agonist, AM1241, dose-dependently reduced STZ-induced hyperalgesia. The results of the present study also demonstrated that inhibitors of COX and NOS increase antihyperalgesic activity of low doses of CB-1 and CB-2 receptor agonists. Hypothetical consequences of this phenomenon are discussed.

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“…In recent years, there has been renewed interest in the use of cannabis for analgesic purposes because of the favorable safety profile of cannabinoids (a group of terpenophenolic compounds present in Cannabis sativa that bind to cannabinoid receptors) [135]. There have been no reported deaths directly attributed to cannabis overdose.…”

Section: Cannabinoidsmentioning

confidence: 99%

“…Although it is not similarly licensed in the UK, it can be imported from Canada for named-patient prescription use. Unfortunately, Review Hill & Schug cannabinoids do not seem to be effective in postoperative pain management being only moderately effective, no different from placebo or even antanalgesic at high doses [135].…”

Section: Cannabinoidsmentioning

confidence: 99%

Recent advances in the pharmaceutical management of pain

Hill

Schug²

2009

Expert Review of Clinical Pharmacology

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Pain is an unpleasant sensory and emotional experience for patients. Management of pain is the most frequent issue encountered by clinicians and treatment is usually with pharmacological therapy. This review discusses recent pharmaceutical advances in pain management with respect to new modes of analgesic delivery, as well as new analgesic agents and adjuvants that are currently being investigated for their analgesic properties. New modes of administration include transdermal delivery in the form of skin patches, transmucosal delivery, inhalational administration, various patient-controlled devices and extended-release analgesic formulations. Up-to-date research is presented on classical analgesics, such as opioids, anti-inflammatory agents, including cyclo-oxygenase-2 inhibitors and paracetamol (acetaminophen), local anesthetics and ketamine. In addition, newer agents such as antidepressants and antiepileptic drugs as well as medicinal cannabinoids are discussed. As our understanding of the multiple pain pathways involved in the pathogenesis of pain expands, further compounds with analgesic properties will be developed.

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Cannabinoids in anaesthesia and pain therapy

Cited by 15 publications

References 30 publications

Activation of CB1 specifically located on GABAergic interneurons inhibits LTD in the lateral amygdala

Activation of CB1 specifically located on GABAergic interneurons inhibits LTD in the lateral amygdala

Effect of Cannabinoid Receptor Agonists on Streptozotocin-Induced Hyperalgesia in Diabetic Neuropathy

Recent advances in the pharmaceutical management of pain

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