Effect of resiniferatoxin on the noxious heat threshold temperature in the rat: a novel heat allodynia model sensitive to analgesics

Almási, Róbert; Pethő, Gábor; Bölcskei, Kata; Szolcsányi, Janós

doi:10.1038/sj.bjp.0705234

Cited by 65 publications

(64 citation statements)

References 36 publications

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“…TRPV1 channels in the skin are involved in the so-called hot-plate response to noxious heat (Almasi et al, 2003). To test whether TRPV1 channels in the skin are desensitized, a rat was transferred from its home cage to a hot-plate apparatus (IITC Life Sciences, Woodland Hills, CA), the floor of which was maintained at 55°C.…”

Section: Desensitization Testsmentioning

confidence: 99%

Nonthermal Activation of Transient Receptor Potential Vanilloid-1 Channels in Abdominal Viscera Tonically Inhibits Autonomic Cold-Defense Effectors

Steiner¹,

Turek²,

Almeida³

et al. 2007

J. Neurosci.

202

242

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An involvement of the transient receptor potential vanilloid (TRPV) 1 channel in the regulation of body temperature (T b ) has not been established decisively. To provide decisive evidence for such an involvement and determine its mechanisms were the aims of the present study. We synthesized a new TRPV1 antagonist, AMG0347 [(E)-N-(7-hydroxy-5,6,7,8-tetrahydronaphthalen-1-yl)-3-(2-(piperidin-1-yl)-6-(trifluoromethyl)pyridin-3-yl)acrylamide], and characterized it in vitro. We then found that this drug is the most potent TRPV1 antagonist known to increase T b of rats and mice and showed (by using knock-out mice) that the entire hyperthermic effect of AMG0347 is TRPV1 dependent. AMG0347-induced hyperthermia was brought about by one or both of the two major autonomic cold-defense effector mechanisms (tail-skin vasoconstriction and/or thermogenesis), but it did not involve warmth-seeking behavior. The magnitude of the hyperthermic response depended on neither T b nor tail-skin temperature at the time of AMG0347 administration, thus indicating that AMG0347-induced hyperthermia results from blockade of tonic TRPV1 activation by nonthermal factors. AMG0347 was no more effective in causing hyperthermia when administered into the brain (intracerebroventricularly) or spinal cord (intrathecally) than when given systemically (intravenously), which indicates a peripheral site of action. We then established that localized intra-abdominal desensitization of TRPV1 channels with intraperitoneal resiniferatoxin blocks the T b response to systemic AMG0347; the extent of desensitization was determined by using a comprehensive battery of functional tests. We conclude that tonic activation of TRPV1 channels in the abdominal viscera by yet unidentified nonthermal factors inhibits skin vasoconstriction and thermogenesis, thus having a suppressive effect on T b .

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Section: Desensitization Testsmentioning

confidence: 99%

Nonthermal Activation of Transient Receptor Potential Vanilloid-1 Channels in Abdominal Viscera Tonically Inhibits Autonomic Cold-Defense Effectors

Steiner¹,

Turek²,

Almeida³

et al. 2007

J. Neurosci.

202

242

View full text Add to dashboard Cite

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“…The noxious heat thresholds for heat allodynia were measured using an increasing-temperature hot plate (IITC Life Science, Woodland Hills, CA, USA) that was recently validated. 24 After habituation, the rats were placed onto the plate that was then heated from a starting temperature of 30°C at a rate of 12°CÁmin -1 until the animal showed nocifensive behaviour involving either hindpaw. The typical response was hindpaw licking, shaking, and lifting.…”

Section: Behavioural Testsmentioning

confidence: 99%

Attenuation of neuropathy-induced allodynia following intraplantar injection of pregabalin

Park

Joo

Chang

et al. 2010

Can J Anesth/J Can Anesth

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Purpose Pregabalin exhibits potent anticonvulsant, analgesic, and anxiolytic activity in animal models. However, few studies have evaluated pregabalin's potential peripheral effects on neuropathic pain. The aim of this study was to evaluate the peripheral analgesic effects of pregabalin in a rat model of neuropathic pain. Methods Male Sprague-Dawley rats were prepared by ligating the left L5 and L6 spinal nerves to produce neuropathic pain. Sixty rats with neuropathic pain were randomly assigned to six groups. Normal saline (control) and pregabalin (10,20,30, and 50 mgÁkg -1 ) were administered to the plantar surface of the affected left hind paw. Pregabalin (50 mgÁkg -1 ) was administered into the unaffected contralateral paw in order to determine its systemic effect. Responses to mechanical, cold, and heat stimulation were recorded at 15,30, 60, 90, 120, 150, and 180 min after drug administration. Rotarod performance was measured to detect drug-induced side effects, including sedation and reduced motor coordination. Results Saline injected into the affected paw and a pregabalin dose of 50 mgÁkg -1 injected into the contralateral paw showed no differences for mechanical, cold, and heat allodynia. Administration of pregabalin to the affected left hind paw in the dose range of 10-50 mgÁkg -1 resulted in a dose-dependent increase in thresholds to mechanical, cold, and heat stimulation. Conclusion Peripherally administered pregabalin attenuates mechanical, cold, and heat allodynia in a rat model of neuropathic pain. RésuméObjectif La pre´gabaline de´montre une puissante activiteá nticonvulsivante, analge´sique et anxiolytique dans les mode`les animaux. Ne´anmoins, il n'existe que peu d'e´tudes ayant e´value´les effets pe´riphe´riques potentiels de la pre´gabaline sur la douleur neuropathique. L'objectif de cette e´tude e´tait d'examiner les effets analge´siques pe´riphe´riques de la pre´gabaline dans un mode`le de douleur neuropathique chez le rat. Méthode Des rats Sprague-Dawley maˆles ont e´teṕ re´pare´s en ligaturant les nerfs rachidiens L5 et L6 afin de cre´er une douleur neuropathique. Soixante rats souffrant de douleur neuropathique ont e´te´ale´atoirement re´partis en six groupes. Du se´rum physiologique (te´moin) et de la pre´gabaline (10, 20, 30, et 50 mgÁkg -1 ) ont e´te´administre´s a`la surface plantaire de la patte arrie`re gauche affecte´e. De la pre´gabaline (50 mgÁkg -1 ) a e´te´administre´e à la patte controlate´rale non affecte´e afin de de´terminer son effet syste´mique. Les re´actions aux stimulations me´caniques, au froid et a`la chaleur ont e´te´enregistre´es a1 5, 30, 60, 90, 120, 150 et 180 min apre`s l'administration du me´dicament. La performance au test de la tige tournante a e´te´mesure´e afin de de´pister les effets secondaires provoque´s par le me´dicament, notamment la se´dation et une re´duction de la coordination motrice.This article is accompanied by an editorial. Please see Can J Anesth 2010; 57(7).

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“…For mechanical pain threshold evaluation, we determined 50% mechanical paw withdrawal thresholds for the left hindpaw to plantar stimulation with von Frey monofilaments (North Coast Medical) according to an up-down algorithm (Chaplan et al, 1994). We assessed thermal pain thresholds on a hotplate device (WPI; Almási et al, 2003). Briefly, rats were placed in a Plexiglas chamber on the plate at 30°C for 5 min for habituation, and plate temperature was raised at a rate of 6°C/min until the animal exhibited paw licking or withdrawal behaviors (cutoff temperature 50°C).…”

Section: Methodsmentioning

confidence: 99%

“…4). A probable underlying mechanism may be a rise in spinal dopamine release following SNL analogous to that observed after intraplantar carrageenan injections (Gao et al, 2001), because D1R responds to prolonged exposure to dopamine by rapid recycling with high rates of repositioning to the cell membrane (Ariano et al, 1997;Bartlett et al, 2005).…”

Section: Upregulation Of D1lrs Increases Met-enkephalin Availabilitymentioning

confidence: 99%

Dopamine D1-like Receptors Regulate Constitutive, μ-Opioid Receptor-Mediated Repression of Use-Dependent Synaptic Plasticity in Dorsal Horn Neurons: More Harm than Good?

et al. 2016

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The current study reports on a synaptic mechanism through which D1-like receptors (D1LRs) modulate spinal nociception and plasticity by regulating activation of the -opioid receptor (MOR).D1LR stimulation with agonist SKF 38393 concentration-dependently depressed C-fiber-evoked potentials in rats receiving spinal nerve ligation (SNL), but not in uninjured rats. Depression was prevented by MOR-but not GABA-receptor blockade. Neurons expressing the D1 subtype were immunopositive for met-enkephalin and vesicular glutamate transporter VGLUT2, but not for GABAergic marker vGAT.Nerve ligation was followed by increased immunoreactivity for D1 in synaptic compartment (P3) in dorsal horn homogenates and presynaptic met-enkephalin-containing boutons. SNL led to increased immunoreactivity for met-enkephalin in dorsal horn homogenates, which was dose-dependently attenuated by selective D1LR antagonist SCH 23390. During blockade of either D1R or MOR, lowfrequency (0.2 or 3 Hz) stimulation (LFS) to the sciatic nerve induced long-term potentiation (LTP) of C-fiber-evoked potentials, revealing a constituent role of both receptors in repressing afferent-induced synaptic plasticity. LFS consistently induced NMDA receptor-dependent LTP in nerve-injured rats. The ability of MOR both to prevent LTP and to modulate mechanical and thermal pain thresholds in behavioral tests was preserved in nerve-ligated rats that were postoperatively treated with SCH 23390. D1LR priming for 30 min sufficed to disrupt MOR function in otherwise naive rats via a mechanism involving receptor overuse.The current data support that, whereas D1LR-modulated MOR activation is instrumental in antinociception and endogenous repression of synaptic plasticity, this mechanism deteriorates rapidly by sustained use, generating increased vulnerability to afferent input.

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Effect of resiniferatoxin on the noxious heat threshold temperature in the rat: a novel heat allodynia model sensitive to analgesics

Cited by 65 publications

References 36 publications

Nonthermal Activation of Transient Receptor Potential Vanilloid-1 Channels in Abdominal Viscera Tonically Inhibits Autonomic Cold-Defense Effectors

Nonthermal Activation of Transient Receptor Potential Vanilloid-1 Channels in Abdominal Viscera Tonically Inhibits Autonomic Cold-Defense Effectors

Attenuation of neuropathy-induced allodynia following intraplantar injection of pregabalin

Dopamine D1-like Receptors Regulate Constitutive, μ-Opioid Receptor-Mediated Repression of Use-Dependent Synaptic Plasticity in Dorsal Horn Neurons: More Harm than Good?

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