Nalfurafine, the kappa opioid agonist, inhibits icilin-induced wet-dog shakes in rats and antagonizes glutamate release in the dorsal striatum

Werkheiser, Jennifer L.; Cowan, Alan

doi:10.1016/j.neuropharm.2006.10.010

Cited by 14 publications

(12 citation statements)

References 46 publications

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“…This idea is supported by the fact that icilin-induced WDS are blocked by central administration of opioids 31, 33, 35, 36, but not by ICI 20448, a peripherally directed kappa opioid agonists 34. Glutamatergic signaling originating in the periphery is required for i.m.…”

Section: Discussionmentioning

confidence: 97%

Dose-Dependent Effects of Icilin on Thermal Preference in the Hindpaw and Face of Rats

Rossi

Vierck

Caudle

et al. 2009

The Journal of Pain

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Icilin induces wet dog shakes (WDS) in rodents when injected systemically and activates the cold receptor TRPM8 and putative cold receptor TRPA1. It is assumed that WDS reflect an enhanced cold sensitivity; however, none have examined the relationship between WDS and cutaneous cold sensitivity following systemic icilin. In this study, we sought to characterize the effect of systemic and central icilin administration on WDS and thermal preference with either hindpaw or facial stimulation. It was found that a low dose of icilin (0.025mg), which transiently elevated WDS, decreased preference for cold with hindpaw stimulation (15 and 45°C) when administered i.p. or i.t. Intracisternal administration of this dose produced similar results for facial stimulation (10 and 48°C), but had no effect when administered i.p. In contrast a high dose of icilin (0.25mg), which persistently elevated WDS, strongly increased preference for cold with hindpaw stimulation and had no effect on thermal preference with facial stimulation. These findings indicate that at the low concentration, systemic and central icilin enhances cold sensitivity, likely via TRPM8 and TRPA1 activation. In contrast, systemic icilin at the high concentration produces peripheral and/or central effects that diminish cold sensitivity, while WDS is maintained at a persistent rate.Perspective-Icilin is a unique compound that produces dissociable effects on an innate behavior (WDS) and on operant behaviors related to thermal perception. This compound could help clarify the relationship between peripheral cold transduction and the central induction of thermogenesis and nocifensive behaviors, as well as alterations that produce pathological pain.

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Section: Discussionmentioning

confidence: 97%

Dose-Dependent Effects of Icilin on Thermal Preference in the Hindpaw and Face of Rats

Rossi

Vierck

Caudle

et al. 2009

The Journal of Pain

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“…Extracellular-regulated protein kinase (ERK) and PIP2 metabolism by PLC activation have been shown to modulate TRPA1 to alter thermal hypersensitivity (Dai et al, 2007; Katsura et al, 2007; Mizushima et al, 2007). Opioid receptor activation antagonizes icilin-induced wet-dog shaking behavior that may be mediated via TRPA1 and/or TRPM8 (Werkheiser et al, 2007). In certain conditions, TRPA1 may be ubiquitinated that may play a role in cancer (Stokes et al, 2006).…”

Section: Transient Receptor Potential Ankyrin 1 (Trpa1)mentioning

confidence: 99%

TRP channels and analgesia

2013

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Since cloning and characterizing the first nociceptive ion channel Transient Receptor Potential (TRP) Vanilloid 1 (TRPV1), other TRP channels involved in nociception have been cloned and characterized, which include TRP Vanilloid 2 (TRPV2), TRP Vanilloid 3 (TRPV3), TRP Vanilloid 4 (TRPV4), TRP Ankyrin 1 (TRPA1) and TRP Melastatin 8 (TRPM8), more recently TRP Canonical 1, 5, 6 (TRPC1, 5, 6), TRP Melastatin 2 (TRPM2) and TRP Melastatin 3 (TRPM3). These channels are predominantly expressed in C and Aδ nociceptors and transmit noxious thermal, mechanical and chemical sensitivities. TRP channels are modulated by pro-inflammatory mediators, neuropeptides and cytokines. Significant advances have been made targeting these receptors either by antagonists or agonists to treat painful conditions. In this review, we will discuss TRP channels as targets for next generation analgesics and the side effects that may ensue as a result of blocking/activating these receptors, because they are also involved in physiological functions such as release of vasoactive neuropeptides and regulation of vascular tone, maintenance of the body temperature, gastrointestinal motility, urinary bladder control etc.

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“…Icilin is a cold-inducing compound that produces a behavioral stimulant effect comprised of WDS, hyperthermia, writhing, and excessive grooming in rats following intraperitoneal injection (Collier, 1974; Wei, 1976, 1981; Collier et al, 1981; Cowan and Watson, 1978; Cowan, 1981; Werkheiser et al, 2006, 2007, 2009; Ding et al, 2008). Consistent with prior work, icilin elicited a dose-dependent increase in shaking behavior in rats in the present experiments.…”

Section: Discussionmentioning

confidence: 99%

“…Despite the potential of TRPM8 ligands as analgesic, antipruritic and antiarthritic agents, the endogenous and exogenous substances that modulate their pharmacological effects in vivo are largely unknown. The trademark overt pharmacological effect of icilin in rats is vigorous wet-dog shakes (WDS) (Wei, 1976, 1981; Werkheiser et al, 2006, 2007, 2009), and this shaking behavior provides a sensitive, reproducible, and quantifiable endpoint to investigate TRPM8 pharmacology in vivo and to identify, and exclude, receptor systems that shape the pharmacological response to TRPM8 channel activation.…”

Section: Introductionmentioning

confidence: 99%

Icilin-evoked behavioral stimulation is attenuated by alpha2-adrenoceptor activation

et al. 2011

Self Cite

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Icilin is a transient receptor potential cation channel subfamily M (TRPM8) agonist that produces behavioral activation in rats and mice. Its hallmark overt pharmacological effect is wet-dog shakes (WDS) in rats. The vigorous shaking associated with icilin is dependent on NMDA receptor activation and nitric oxide production, but little else is known about the biological systems that modulate the behavioral phenomenon. The present study investigated the hypothesis that alpha2-adrenoceptor activation inhibits icilin-induced WDS. Rats injected with icilin (0.5, 1, 2.5, 5 mg/kg, i.p.) displayed dose-related WDS that were inhibited by pretreatment with a fixed dose of clonidine (0.15 mg/kg, s.c.). Shaking behavior caused by a fixed dose (2.5 mg/kg) of icilin was also inhibited in a dose-related manner by clonidine pretreatment (0.03–0.15 mg/kg, s.c.) and reduced by clonidine posttreatment (0.15 mg/kg, s.c.). Pretreatment with a peripherally restricted alpha2-adrenoceptor agonist, ST91 (0.075, 0.15 mg/kg), also decreased the incidence of shaking elicited by 2.5 mg/kg of icilin. Pretreatment with yohimbine (2 mg/kg, i.p.) enhanced the shaking induced by a low dose of icilin (0.5 mg/kg). The imidazoline site agonists, agmatine (150 mg/kg, i.p.) and 2-BFI (7 mg/kg, i.p.), did not affect icilin-evoked shaking. These results suggest that alpha2-adrenoceptor activation inhibits shaking induced by icilin and that increases in peripheral, as well as central, alpha2-adrenoceptor signaling oppose the behavioral stimulant effect of icilin.

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Nalfurafine, the kappa opioid agonist, inhibits icilin-induced wet-dog shakes in rats and antagonizes glutamate release in the dorsal striatum

Cited by 14 publications

References 46 publications

Dose-Dependent Effects of Icilin on Thermal Preference in the Hindpaw and Face of Rats

Dose-Dependent Effects of Icilin on Thermal Preference in the Hindpaw and Face of Rats

TRP channels and analgesia

Icilin-evoked behavioral stimulation is attenuated by alpha2-adrenoceptor activation

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