Long-term depression of nociceptive synapses by non-nociceptive afferent activity: Role of endocannabinoids, Ca2+, and calcineurin

Yuan, Sharleen; Burrell, Brian D.

doi:10.1016/j.brainres.2012.04.030

Cited by 17 publications

(35 citation statements)

References 71 publications

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“…The concentration of SB366791 was chosen based on the elevated concentrations of capsaicin required to elicit a response in the lN cell. However, lower concentrations of SB366791 (10 μmol l −1 ) have been shown previously to be effective at blocking the effects of capsaicin (10 μmol l −1 ) on central synapses (Yuan and Burrell, 2012). These results are consistent with the hypothesis that peripheral and central responses to capsaicin are mediated by a TRPV-like receptor.…”

supporting

confidence: 89%

“…The endocannabinoids and endovanilloids AEA and 2-AG are present in the leech CNS (Matias et al, 2001), yet the leech and other protostomal invertebrates lack orthologs to the CB1 and CB2 receptors (Elphick, 2012). There is, however, evidence that central TRPV-like channels mediate synaptic plasticity in the leech via mechanisms that are similar to those observed in vertebrates (Li and Burrell, 2010;Yuan and Burrell, 2010;Li and Burrell, 2011;Yuan and Burrell, 2012; Higgins et al, 2013;Yuan and Burrell, 2013). …”

mentioning

confidence: 97%

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Physiological and behavioral evidence of a capsaicin sensitive TRPV-like channel in the medicinal leech

Summers

Holec

Burrell

2014

Journal of Experimental Biology

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Transient receptor potential vanilloid (TRPV) channels are found throughout the animal kingdom, where they play an important role in sensory transduction. In this study, we combined physiological studies with in vivo behavioral experiments to examine the presence of a putative TRPV-like receptor in the medicinal leech, building upon earlier studies in this lophotrochozoan invertebrate. The leech polymodal nociceptive neuron was activated by both peripheral and central application of the TRPV1-activator capsaicin in a concentration-dependent manner, with 100 μmol l −1 being the lowest effective concentration. Responses to capsaicin were inhibited by the selective TRPV1 antagonist SB366791. The polymodal nociceptive neuron also responded to noxious thermal stimuli (>40°C), and this response was also blocked by SB366791. Capsaicin sensitivity was selective to the polymodal nociceptor with no direct response being elicited in the mechanical nociceptive neuron or in the nonnociceptive touch-or pressure-sensitive neurons. Capsaicin also elicited nocifensive behavioral responses (withdrawals and locomotion) in a concentration-dependent manner, and these behavioral responses were significantly attenuated with SB366791. These results suggest the presence of a capsaicin-sensitive TRPVlike channel in the medicinal leech central nervous system and are relevant to the evolution of nociceptive signaling. KEY WORDS: Leech, TRPV, Invertebrate, Nociception INTRODUCTIONTransient receptor potential (TRP) channels are a diverse class of non-specific cation channels that are found throughout the animal kingdom (Damann et al., 2008). TRP channels are typically associated with sensory transduction and are often polymodal, such as the mammalian TRP-vanilloid 1 (TRPV1) channel, which responds to noxious thermal (>42°C), mechanical and chemical (low pH, capsaicin) stimuli (Szallasi and Blumberg, 1999). Capsaicin sensitivity varies greatly throughout metazoans, with mammals displaying the greatest response to capsaicin. Birds, once thought to be capsaicin insensitive, have been shown to respond to capsaicin at increased concentrations (30 μmol l −1 ) compared with mammals (Kirifides et al., 2004). Even among mammals, capsaicin sensitivity varies greatly between species, and this variance is further complicated by ontogentic shifts in capsaicin sensitivity within specific strains of mice (Holzer, 1991). Invertebrate sensitivity to capsaicin is no less complicated because ecdysozoans, such as Drosophila (Vriens et al., 2004) and Caenorhabditis elegans (Tobin RESEARCH ARTICLECenter for Brain and Behavior Research, Division of Basic Biomedical Sciences, Sanford, School of Medicine, University of South Dakota, Vermillion, SD 57069, USA. *Author for correspondence (bburrell@usd.edu)Received 23 June 2014; Accepted 7 October 2014 et al., 2002), are reported to be capsaicin insensitive, whereas lophotrochozoans, specifically the gastropod Megalobulimus (KalilGaspar et al., 2007) and the medicinal leech (Hirudo verbana, Carena 1820) (Pasto...

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supporting

confidence: 89%

mentioning

confidence: 97%

Physiological and behavioral evidence of a capsaicin sensitive TRPV-like channel in the medicinal leech

Summers

Holec

Burrell

2014

Journal of Experimental Biology

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“…Endocannabinoids have been proposed as a potential therapeutic approach for treating epilepsy, presumably due to their ability to elicit persistent depression of glutamatergic synapses (Marsicano et al 2003;Katona and Freund 2008;Izzo et al 2009;Bhaskaran and Smith 2010;Zurolo et al 2010). In the leech, 2-AG and the synthetic cannabinoid CP 55,940 have been observed to induce long-lasting depression in glutamatergic synapses utilizing cellular mechanisms that are remarkably similar to those responsible for endocannabinoid-dependent long-term depression (eCB-LTD) in the mammalian brain Burrell 2009, 2010;Yuan and Burrell 2010;Li and Burrell 2011;Katona and Freund 2012;Yuan and Burrell 2012). One difference is that the leech, like other protostomal invertebrates, lack orthologues to the mammalian CB1 and CB2 receptors (Elphick 2012).…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, it is possible that there is an interaction between the effects of fluoxetine and those of 2-AG. Activation of serotonin receptors has been shown to stimulate endocannabinoid synthesis and to be required for some forms of endocannabinoid-mediated neuroplasticity including in both the mammalian and leech's nervous systems (Iskedjian et al 2007;Li and Burrell 2010;Yuan and Burrell 2012;Hiroi et al 2013). It is possible that fluoxetine-induced increases in serotonin lead to an enhanced levels of 2-AG, which in turn reduce hyperactivity that may lead to seizures.…”

Section: Discussionmentioning

confidence: 99%

“…The leech's central nervous system (CNS) is relatively simple, in terms of number of neurons, and is well characterized with respect to the identity, functional role, and connectivity of many individual cells (Muller et al 1981). The physiological processes of the leech and mammalian nervous system are very similar in terms of the neurotransmitters and their receptors, mechanisms of neuroplasticity, and the organization of neurons into functional circuits (Kristan et al 2005;Mazzoni et al 2007;Grey and Burrell 2010;Li and Burrell 2011;Yuan and Burrell 2012). Consequently, discoveries made about seizure-like activity in the leech are likely to be applicable to the human CNS.…”

Section: Introductionmentioning

confidence: 99%

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Pentylenetetrazol-induced seizure-like behavior and neural hyperactivity in the medicinal leech

Hahn

Burrell

2015

Invert Neurosci

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This study examined the capacity of a known pro-epileptic drug, pentylenetetrazol (PTZ), to elicit seizure-like activity in the medicinal leech, Hirudo verbana. During in vivo experiments, PTZ elicited increased motor activity in a concentration-dependent manner with the highest concentration (10 mM) eliciting episodes of highly uncoordinated exploratory and swimming behavior. Co-application of the anti-epileptic drug, phenytoin, failed to reduce the absolute amount of PTZ-induced motor behavior, but was able to prevent expression of abnormal exploratory and swimming behaviors. During in vitro experiments in which extracellular recordings of connective nerve activity were made, bath application of 1 μM PTZ in Mg(2+)-free saline elicited a significant increase in spontaneous activity. This PTZ-induced increase in activity was completely inhibited by phenytoin. Interestingly, PTZ-induced hyperactivity was also blocked by co-application of the endocannabinoid 2-arachidonoyl glycerol and the selective serotonin re-uptake inhibitor (SSRI) fluoxetine. These findings suggest that the leech can be a useful system in which to study potential anti-epileptic treatments.

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TRPV1 in the Central Nervous System: Synaptic Plasticity, Function, and Pharmacological Implications

Edwards

2014

Capsaicin as a Therapeutic Molecule

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Long-term depression of nociceptive synapses by non-nociceptive afferent activity: Role of endocannabinoids, Ca2+, and calcineurin

Cited by 17 publications

References 71 publications

Physiological and behavioral evidence of a capsaicin sensitive TRPV-like channel in the medicinal leech

Physiological and behavioral evidence of a capsaicin sensitive TRPV-like channel in the medicinal leech

Pentylenetetrazol-induced seizure-like behavior and neural hyperactivity in the medicinal leech

TRPV1 in the Central Nervous System: Synaptic Plasticity, Function, and Pharmacological Implications

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