Approaches to studying injury-induced sensitization and the potential role of an endocannabinoid transmitter

Jorgensen, Megan; Burrell, Brian D.

doi:10.1007/s00359-021-01540-z

Cited by 6 publications

(6 citation statements)

References 48 publications

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“…2 (referred to as non-injured–day 1), an injured group of animals tested on the same day as injury (injured–day 1; N =10), and a group that was injured but not tested until 7 days later (injured–day 7; N =6). The injury consisted of a piercing of the posterior sucker using a -pin, which has been validated in a previous H. verbana study as producing non-nociceptive sensitization that lasts 7 days as well as short-term (<1 day) nociceptive sensitization ( Jorgensen and Burrell, 2022 ).…”

Section: Resultsmentioning

confidence: 99%

“…NMDA receptors are known to contribute to wind-up sensitization in mammals and repeated high-frequency stimulation of Hirudo nociceptors is known to produce NMDA receptor-dependent synaptic potentiation in nociceptive and non-nociceptive synapses ( Franzen et al, 2023 ; Yuan and Burrell, 2019 ). Other physiological mechanisms potentially contributing to sensitization in Hirudo include decreases in GABAergic tone (disinhibition) ( Baca et al, 2008 ; Paulsen and Burrell, 2022 ), endocannabinoid-based modulation ( Jorgensen and Burrell, 2022 ; Wang and Burrell, 2018 ) and serotonergic modulation ( Burrell and Sahley, 2005 ; Burrell et al, 2001 ; Ehrlich et al, 1992 ; Lockery and Kristan, 1991 ; Zaccardi et al, 2004 ).…”

Section: Discussionmentioning

confidence: 99%

“…Immediately after injury, H. verbana were transferred to the Petri dish with room temperature pond water. This approach has been shown to elicit a consistent level of sensitization to subsequent mechanical stimuli applied to the sucker lasting at least 7 days ( Jorgensen and Burrell, 2022 ). Following the acclimation period in the Petri dish, the leeches received repetitive stimulation with the 25 gauge needle ( Fig.…”

Section: Methodsmentioning

confidence: 99%

“…Our group has used the medicinal leech, Hirudo verbana , to study neuromodulation in nociceptive and non-nociceptive synapses and the impact of such modulation on behavior ( Hanson and Burrell, 2018 ; Jorgensen and Burrell, 2022 ; Paulsen and Burrell, 2019 ; Wang and Burrell, 2018 ; Yuan and Burrell, 2013 ). Hirudo possess a complement of somatic sensory neurons similar to those found in vertebrates ( Smith and Lewin, 2009 ).…”

Section: Introductionmentioning

confidence: 99%

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Repetitive nociceptive stimulation elicits complex behavioral changes in Hirudo: evidence of arousal and motivational adaptations

Hoynoski,

Dohn,

Franzen

et al. 2023

Journal of Experimental Biology

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Appropriate responses to real or potential damaging stimuli to the body (nociception) are critical to an animal's short- and long-term survival. The initial goal of this study was to examine habituation of withdrawal reflexes (whole-body and local shortening) to repeated mechanical nociceptive stimuli (needle pokes) in the medicinal leech, Hirudo verbana, and assess whether injury altered habituation to these nociceptive stimuli. While repeated needle pokes did reduce shortening in Hirudo, a second set of behaviors changes was observed. Specifically, animals began to evade subsequent stimuli by either hiding their posterior sucker underneath adjacent body segments or by engaging in locomotion (crawling). Animals differed in terms of how quickly they adopted evasion behaviors during repeated stimulation, exhibiting a multi-modal distribution for early, intermediate, and later evaders. Prior injury had a profound effect on this transition, decreasing the time frame in which animals began to carry out evasion and increasing the magnitude of these evasion behaviors (more locomotory evasion). The data indicate the presence in Hirudo of a complex and adaptive defensive arousal process to avoid noxious stimuli that is influenced by differences in internal states, prior experience with injury of the stimulated areas, and possibly learning-based processes.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Repetitive nociceptive stimulation elicits complex behavioral changes in Hirudo: evidence of arousal and motivational adaptations

Hoynoski,

Dohn,

Franzen

et al. 2023

Journal of Experimental Biology

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“…Transient receptor potential (TRP) channels have been observed as potential endocannabinoid receptors in Drosophila and Hirudo verbana [15,23,24]. Previous work in our laboratory has used the medicinal leech (Hirudo verbana) to study endocannabinoid modulation of nociception at the physiological and behavioral level [12,[24][25][26][27], including characterizing critical proteins such as MAGL [20]. In this study we identify a gene encoding the Hirudo orthologue of FAAH, assessing its biochemical activity, pharmacology, and potential physiological/synaptic role.…”

Section: Introductionmentioning

confidence: 99%

Characterization of a Fatty Acid Amide Hydrolase (FAAH) in Hirudo verbana

Kabeiseman,

Paulsen,

Burrell

2024

Preprint

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The endocannabinoid system plays a critical role in modulating both peripheral and central nervous system function. Despite being present throughout the animal kingdom, there has been relatively little investigation of the endocannabinoid system beyond the traditional animal model systems. In this study, we report on the identification and characterization of a fatty acid aminohydrolase (FAAH) in the medicinal leech, Hirudo verbana. FAAH is the primary enzyme responsible for metabolizing the endocannabinoid signaling molecule arachidonoyl ethanolamide (anandamide or AEA) and therefore plays a critical role in regulating AEA levels in the nervous system. This Hirudo FAAH (HirFAAH) is expressed in the leech central nervous system (CNS) and is an orthologue of FAAH-2 observed in vertebrates. Functionally, HirFAAH has serine hydrolase activity based on activity-based protein profiling (ABPP) studies using the fluorophosphonate probe TAMRA-FP. HirFAAH also hydrolyzes arachidonyl 7-amino, 4-methyl coumarin amide (AAMCA), a substrate specific to FAAH. Hydrolase activity during both the ABPP and AAMCA assays was eliminated by mutation at a conserved activity-binding site. Activity was also blocked by the known FAAH inhibitor, URB597. Treatment of Hirudo ganglia with URB597 potentiated synapses made by the pressure-sensitive mechanosensory neuron (P cell), mimicking the effects of exogenously applied AEA. The Hirudo CNS has been a useful system in which to study properties of endocannabinoid modulation of nociception relevant to vertebrates. Therefore, this characterization of HirFAAH is an important contribution to comparative studies of the endocannabinoid system.

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Characterization of a Fatty Acid Amide Hydrolase (FAAH) in Hirudo Verbana

Kabeiseman,

Paulsen,

Burrell

2024

Neurochem Res

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The endocannabinoid system plays a critical role in modulating both peripheral and central nervous system function. Despite being present throughout the animal kingdom, there has been relatively little investigation of the endocannabinoid system beyond traditional animal models. In this study, we report on the identification and characterization of a putative fatty acid amide hydrolase (FAAH) in the medicinal leech, Hirudo verbana. FAAH is the primary enzyme responsible for metabolizing the endocannabinoid signaling molecule arachidonoyl ethanolamide (anandamide or AEA) and therefore plays a critical role in regulating AEA levels in the nervous system. mRNA encoding Hirudo FAAH (HirFAAH) is expressed in the leech central nervous system (CNS) and sequence analysis suggests that this is an orthologue of FAAH-2 observed in vertebrates. Functionally, HirFAAH has serine hydrolase activity based on activity-based protein profiling (ABPP) studies using the fluorophosphonate probe TAMRA-FP. HirFAAH also hydrolyzes arachidonyl 7-amino, 4-methyl coumarin amide (AAMCA), a substrate specific to FAAH. Hydrolase activity during both the ABPP and AAMCA assays was eliminated by a mutation at a conserved catalytic serine. Activity was also blocked by the known FAAH inhibitor, URB597. Treatment of Hirudo ganglia with URB597 potentiated synapses made by the pressure-sensitive mechanosensory neuron (P cell), mimicking the effects of exogenously applied AEA. The Hirudo CNS has been a useful system in which to study properties of endocannabinoid modulation of nociception relevant to vertebrates. Therefore, this characterization of HirFAAH is an important contribution to comparative studies of the endocannabinoid system.

show abstract

Approaches to studying injury-induced sensitization and the potential role of an endocannabinoid transmitter

Cited by 6 publications

References 48 publications

Repetitive nociceptive stimulation elicits complex behavioral changes in Hirudo: evidence of arousal and motivational adaptations

Repetitive nociceptive stimulation elicits complex behavioral changes in Hirudo: evidence of arousal and motivational adaptations

Characterization of a Fatty Acid Amide Hydrolase (FAAH) in Hirudo verbana

Characterization of a Fatty Acid Amide Hydrolase (FAAH) in Hirudo Verbana

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