Antihyperalgesic effects of spinal cannabinoids

Richardson, Jennelle Durnett; Aanonsen, Lin; Hargreaves, Kenneth M.

doi:10.1016/s0014-2999(97)01621-x

Cited by 253 publications

(125 citation statements)

References 18 publications

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“…Intrathecal administration of the non-selective cannabinoid receptor agonist anandamide blocks the thermal hyperalgesia caused by carrageenan injection into the rat hindpaw (Richardson et al, 1998a). Similarly, intrathecal administration of another non-selective cannabinoid receptor agonist, WIN55,212-2, reverses the mechanical allodynia or hyperalgesia induced by injection of complete Freund's adjuvant into the rat hindpaw (Martin et al, 1999) or partial ligation of the sciatic nerve (Fox et al, 2001).…”

Section: Antinociceptive Effect Of Cannabinoid Receptor Agonistsmentioning

confidence: 99%

Modulation of pain transmission by G-protein-coupled receptors

Pan

Zhou

et al. 2008

Pharmacology & Therapeutics

169

116

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The heterotrimeric G protein-coupled receptors (GPCRs) represent the largest and most diverse family of cell surface receptors and proteins. GPCRs are widely distributed in the peripheral and central nervous systems and are one of the most important therapeutic targets in pain medicine. GPCRs are present on the plasma membrane of neurons and their terminals along the nociceptive pathways and are closely associated with the modulation of pain transmission. GPCRs that can produce analgesia upon activation include opioid, cannabinoid, α 2 -adrenergic, muscarinic acetylcholine, γ-aminobutyric acid B (GABA B ), group II and III metabotropic glutamate, and somatostatin receptors. Recent studies have led to a better understanding of the role of these GPCRs in the regulation of pain transmission. Here, we review the current knowledge about the cellular and molecular mechanisms that underlie the analgesic actions of GPCR agonists, with a focus on their effects on ion channels expressed on nociceptive sensory neurons and on synaptic transmission at the spinal cord level.

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Section: Antinociceptive Effect Of Cannabinoid Receptor Agonistsmentioning

confidence: 99%

Modulation of pain transmission by G-protein-coupled receptors

Pan

Zhou

et al. 2008

Pharmacology & Therapeutics

169

116

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“…A CB 2 -mediated effect exists, consisting in the indirect stimulation of opioid receptors located in primary afferent pathways [67], as will be described in more detail in the next section. Thus, cannabinoid compounds can modulate hyperalgesia of various origins and they are effective even in inflammatory and neuropathic pain [10,133], which are conditions often refractory to treatment. In the CNS, although CB 2 receptor mRNA has not been detected in the neuronal tissue of human or rat brain, a role in antinociception in inflammatory processes of the nervous system cannot be excluded due to its presence in activated microglia [166].…”

Section: Activation Of Cannabinoid Receptorsmentioning

confidence: 99%

Role of the Cannabinoid System in Pain Control and Therapeutic Implications for the Management of Acute and Chronic Pain Episodes

Manzanares¹,

Julián²,

Carrascosa

2006

231

148

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Cannabis extracts and synthetic cannabinoids are still widely considered illegal substances. Preclinical and clinical studies have suggested that they may result useful to treat diverse diseases, including those related with acute or chronic pain. The discovery of cannabinoid receptors, their endogenous ligands, and the machinery for the synthesis, transport, and degradation of these retrograde messengers, has equipped us with neurochemical tools for novel drug design. Agonist-activated cannabinoid receptors, modulate nociceptive thresholds, inhibit release of pro-inflammatory molecules, and display synergistic effects with other systems that influence analgesia, especially the endogenous opioid system. Cannabinoid receptor agonists have shown therapeutic value against inflammatory and neuropathic pains, conditions that are often refractory to therapy. Although the psychoactive effects of these substances have limited clinical progress to study cannabinoid actions in pain mechanisms, preclinical research is progressing rapidly. For example, CB 1 -mediated suppression of mast cell activation responses, CB 2 -mediated indirect stimulation of opioid receptors located in primary afferent pathways, and the discovery of inhibitors for either the transporters or the enzymes degrading endocannabinoids, are recent findings that suggest new therapeutic approaches to avoid central nervous system side effects. In this review, we will examine promising indications of cannabinoid receptor agonists to alleviate acute and chronic pain episodes. Recently, Cannabis sativa extracts, containing known doses of tetrahydrocannabinol and cannabidiol, have granted approval in Canada for the relief of neuropathic pain in multiple sclerosis. Further double-blind placebo-controlled clinical trials are needed to evaluate the potential therapeutic effectiveness of various cannabinoid agonists-based medications for controlling different types of pain.

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“…In acute pain in particular, cannabinoids inhibit responses to noxious thermal and mechanical stimuli, as well as nociceptive behaviour in the formalin test [50,62,81,88,99]. In more persistent nociceptive states, cannabinoids reduce thermal and mechanical hyperalgesia and mechanical allodynia following peripheral inflammation [61,80], capsaicin injection [47] or peripheral nerve injury [35]. Both the analgesic and hyperalgesic effects of cannabinoids are mediated by CB 1 receptors [9,80], because they are blocked by the selective CB 1 receptor antagonist, SR141716A [82].…”

Section: Cannabinoids and Painmentioning

confidence: 99%

“…In more persistent nociceptive states, cannabinoids reduce thermal and mechanical hyperalgesia and mechanical allodynia following peripheral inflammation [61,80], capsaicin injection [47] or peripheral nerve injury [35]. Both the analgesic and hyperalgesic effects of cannabinoids are mediated by CB 1 receptors [9,80], because they are blocked by the selective CB 1 receptor antagonist, SR141716A [82]. More recently, an inhibition of pain responses mediated by CB 2 receptors has been reported [14,56]; this is relevant from a therapeutical standpoint because selective CB 2 receptor agonists shuould not produce the typical psychoactive effects associated with CB 1 receptor activation.…”

Section: Cannabinoids and Painmentioning

confidence: 99%

Metabotropic Glutamate and Cannabinoid Receptor Crosstalk in Periaqueductal Grey Pain Processing

Palazzos

Novellis²,

Marabese³

et al. 2006

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Metabotropic glutamate (mGlu) and cannabinoid receptors are G-protein coupled receptors which have shown synaptic co-operation through small lipid messengers in the central nervous system (CNS). A functional interaction between these two receptor families could have a relevant potential in the treatment of CNS disorders, including chronic pain. Indeed, both mGlu and cannabinoid receptors play a crucial role in the neurobiology of pain and their simultaneous manipulation could lead to novel strategies in pain management. In particular, as both mGlu and cannabinoid receptors have been found in the periaqueductal gray (PAG), a crucial station in the pain modulatory system, these receptors could be a substrate for producing analgesia at this level. In this review we aim to briefly illustrate the role of mGlu and cannabinoid receptors in controlling nociceptive processes, some points of convergence, and their functional interaction in pain processing. Further insights into this functional linkage between the mGlu and cannabinoid receptors could pave the way to a new strategy for pain relief, such as a drug cocktail acting on cannabinoid/metabotropic glutamate receptors.Key Words: Periaqueductal grey, metabotropic glutamate receptors; cannabinoid receptors, pain. METABOTROPIC GLUTAMATE RECEPTORS AND PAINMetabotropic glutamate (mGlu) receptors play an important role in the modulation of nociceptive processing and central sensitisation associated with persistent and chronic pain at several levels in the CNS [29,42,67,68].Several studies have shown that mGlu receptors modulate nociception from peripheral terminals [5,10,67,98,104]. This may stimulate the search for peripherally active mGlu receptor ligands, which are devoid of central adverse effects [30]. A role for mGlu receptors in spinal nociceptive processing has been reported, with particular emphasis on group I mGlu receptors [13,20,69,70,100,101,102,103]. Stimulation of group I mGlu receptors at spinal level generally produces pro-nociceptive effects [31,100], although functional differences between mGlu 1 and mGlu 5 receptors in modulating pain are recently emerging at the same rate as new selective mGlu receptor ligands are developed [69,90,101]. Spinal group I mGlu receptors also play an important role in nociceptive hypersensitivity associated with inflammation [8,69,101]. Intrathecal application of group II and group III agonists inhibit nociceptive responses [20,70,91], which may reflect the inhibition of glutamate release from nerve endings. Upregulation of mGlu 3 mRNA in the spinal cord following hind paw inflammation has also been reported [6]. A role for supraspinal mGlu receptors in the modulation of pain is also emerging, mGlu receptors modulate nociceptive responses at the level of ventrobasal thalamus [83][84][85], dorsal raphe [72] and amygdala [32,33,48]. This review will *Address correspondence to these authors at Department of Experimental Medicine, Section of Pharmacology "L. Donatelli"-Faculty of Medicine and Surgery, Second Universi...

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Antihyperalgesic effects of spinal cannabinoids

Cited by 253 publications

References 18 publications

Modulation of pain transmission by G-protein-coupled receptors

Modulation of pain transmission by G-protein-coupled receptors

Role of the Cannabinoid System in Pain Control and Therapeutic Implications for the Management of Acute and Chronic Pain Episodes

Metabotropic Glutamate and Cannabinoid Receptor Crosstalk in Periaqueductal Grey Pain Processing

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