The multiplicity of spinal AA-5-HT anti-nociceptive action in a rat model of neuropathic pain

Małek, Natalia; Kostrzewa, Magdalena; Makuch, Wioletta; Pająk, Agnieszka; Kucharczyk, M.; Piscitelli, Fabiana; Przewłocka, Barbara; Marzo, Vincenzo Di; Starowicz, Katarzyna

doi:10.1016/j.phrs.2016.06.012

Cited by 25 publications

(17 citation statements)

References 92 publications

(95 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In contrast, the dual FAAH inhibitor/TRPV1 antagonist compounds AA-5-HT (Hohmann et al, 2005; Maione et al, 2007) and OMDM-198 (Maione et al, 2013) produce antinociception in the absence of hyperthermia. AA-5-HT has antinociceptive efficacy in the formalin and carrageenan models of inflammation, and the CCI and SNI models of neuropathic pain (Costa et al, 2010; de Novellis et al, 2008; de Novellis et al, 2011; Maione et al, 2007; Malek et al, 2016), whilst OMDM-198 is effective in the formalin and carrageenan models of inflammatory pain (Maione et al, 2013), and a rat model of osteoarthritic pain (Malek et al, 2015). A significant supraspinal component to these effects has been described via microinjection of AA-5-HT into the PAG, resulting in CB 1 -, and TRPV1-dependent analgesia, and a restoration of the excitation-inhibition balance in prefrontal cortex (de Novellis et al, 2008; de Novellis et al, 2011).…”

Section: Blockade Of Ec Metabolism As An Analgesic Approach: Past mentioning

confidence: 99%

The cannabinoid system and pain

et al. 2017

View full text Add to dashboard Cite

Chronic pain states are highly prevalent and yet poorly controlled by currently available analgesics, representing an enormous clinical, societal, and economic burden. Existing pain medications have significant limitations and adverse effects including tolerance, dependence, gastrointestinal dysfunction, cognitive impairment, and a narrow therapeutic window, making the search for novel analgesics ever more important. In this article, we review the role of an important endogenous pain control system, the endocannabinoid (EC) system, in the sensory, emotional, and cognitive aspects of pain. Herein, we briefly cover the discovery of the EC system and its role in pain processing pathways, before concentrating on three areas of current major interest in EC pain research; 1. Pharmacological enhancement of endocannabinoid activity (via blockade of EC metabolism or allosteric modulation of CB1 receptors); 2. The EC System and stress-induced modulation of pain; and 3. The EC system & medial prefrontal cortex (mPFC) dysfunction in pain states. Whilst we focus predominantly on the preclinical data, we also include extensive discussion of recent clinical failures of endocannabinoid-related therapies, the future potential of these approaches, and important directions for future research on the EC system and pain.

show abstract

Section: Blockade Of Ec Metabolism As An Analgesic Approach: Past mentioning

confidence: 99%

The cannabinoid system and pain

et al. 2017

View full text Add to dashboard Cite

show abstract

“…It is also activated by abnormal cannabidiol (abn-CBD) that, when infused into regions of the brainstem, causes reduction in blood pressure in a manner that involves nitric oxide synthase and adiponectin signaling (Penumarti and Abdel-Rahman, 2014a ). As with GPR55 discussed above (section GPR55 in CNS), GPR18 receptor expression is upregulated following spinal cord injury; this suggests that it may mediate some of the analgesic effects of N-arachidonoyl-serotonin (AA-5-HT, Malek et al, 2016 ). Notably, the principal active constituent of Cannabis , THC, is a potent agonist of GPR18 when expressed in HEK293 cells (McHugh et al, 2012 ).…”

Section: Non-cb1/cb2 Receptor Targetsmentioning

confidence: 93%

“…Deletion of GPR55 in mice has subtle effects on motor coordination, but it has shown no significant effect on several learning and memory tests, in contrast to the role of CB1 signaling, and despite dense GPR55 expression in hippocampus, striatum, and cortex (Wu et al, 2013 ). Spinal cord expression of GPR55 is upregulated in a chronic constriction injury model of neuropathic pain; this suggests that it may mediate some of the analgesic effects of N-arachidonoyl-serotonin (AA-5-HT, Malek et al, 2016 ). GPR55 activation by some agonists increases calcium release from intraneuronal stores and inhibits M-type potassium current, both tending to promote neuronal activity (Lauckner et al, 2008 ).…”

Section: Non-cb1/cb2 Receptor Targetsmentioning

confidence: 99%

Cannabinoids Modulate Neuronal Activity and Cancer by CB1 and CB2 Receptor-Independent Mechanisms

2017

View full text Add to dashboard Cite

Cannabinoids include the active constituents of Cannabis or are molecules that mimic the structure and/or function of these Cannabis-derived molecules. Cannabinoids produce many of their cellular and organ system effects by interacting with the well-characterized CB1 and CB2 receptors. However, it has become clear that not all effects of cannabinoid drugs are attributable to their interaction with CB1 and CB2 receptors. Evidence now demonstrates that cannabinoid agents produce effects by modulating activity of the entire array of cellular macromolecules targeted by other drug classes, including: other receptor types; ion channels; transporters; enzymes, and protein- and non-protein cellular structures. This review summarizes evidence for these interactions in the CNS and in cancer, and is organized according to the cellular targets involved. The CNS represents a well-studied area and cancer is emerging in terms of understanding mechanisms by which cannabinoids modulate their activity. Considering the CNS and cancer together allow identification of non-cannabinoid receptor targets that are shared and divergent in both systems. This comparative approach allows the identified targets to be compared and contrasted, suggesting potential new areas of investigation. It also provides insight into the diverse sources of efficacy employed by this interesting class of drugs. Obtaining a comprehensive understanding of the diverse mechanisms of cannabinoid action may lead to the design and development of therapeutic agents with greater efficacy and specificity for their cellular targets.

show abstract

“…Because an increase in AEA by an FAAH inhibitor can also act on TRPV1, which has been implicated in the development of neuropathic pain, a dual FAAH and TRPV1 inhibitor, AA-5-HT (N-arachidonoyl-serotonin) has been tested in a neuropathic pain model [207,208]. The compound produced enhanced anti-nociceptive effects in neuropathic pain models in rats compared with separate use of an FAAH inhibitor (PF3845) or a TRPV1 inhibitor (iodoresiniferatoxin) [207].…”

Section: Dual Faah and Trpv1 Inhibitorsmentioning

confidence: 99%

Targeting Peripherally Restricted Cannabinoid Receptor 1, Cannabinoid Receptor 2, and Endocannabinoid-Degrading Enzymes for the Treatment of Neuropathic Pain Including Neuropathic Orofacial Pain

Hossain

Ando

Unno

2020

IJMS

View full text Add to dashboard Cite

Neuropathic pain conditions including neuropathic orofacial pain (NOP) are difficult to treat. Contemporary therapeutic agents for neuropathic pain are often ineffective in relieving pain and are associated with various adverse effects. Finding new options for treating neuropathic pain is a major priority in pain-related research. Cannabinoid-based therapeutic strategies have emerged as promising new options. Cannabinoids mainly act on cannabinoid 1 (CB1) and 2 (CB2) receptors, and the former is widely distributed in the brain. The therapeutic significance of cannabinoids is masked by their adverse effects including sedation, motor impairment, addiction and cognitive impairment, which are thought to be mediated by CB1 receptors in the brain. Alternative approaches have been developed to overcome this problem by selectively targeting CB2 receptors, peripherally restricted CB1 receptors and endocannabinoids that may be locally synthesized on demand at sites where their actions are pertinent. Many preclinical studies have reported that these strategies are effective for treating neuropathic pain and produce no or minimal side effects. Recently, we observed that inhibition of degradation of a major endocannabinoid, 2-arachydonoylglycerol, can attenuate NOP following trigeminal nerve injury in mice. This review will discuss the above-mentioned alternative approaches that show potential for treating neuropathic pain including NOP.

show abstract

The multiplicity of spinal AA-5-HT anti-nociceptive action in a rat model of neuropathic pain

Cited by 25 publications

References 92 publications

The cannabinoid system and pain

The cannabinoid system and pain

Cannabinoids Modulate Neuronal Activity and Cancer by CB1 and CB2 Receptor-Independent Mechanisms

Targeting Peripherally Restricted Cannabinoid Receptor 1, Cannabinoid Receptor 2, and Endocannabinoid-Degrading Enzymes for the Treatment of Neuropathic Pain Including Neuropathic Orofacial Pain

Contact Info

Product

Resources

About