Unilateral hot plate test: a simple and sensitive method for detecting central and peripheral hyperalgesia in mice

Menéndez, Luis; Lastra, Ana; Hidalgo, Agustı́n; Baamonde, Ana

doi:10.1016/s0165-0270(01)00483-6

Cited by 126 publications

(64 citation statements)

References 18 publications

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“…For detailed methods refer to SI Material and Methods. Briefly, thermal nociceptive responses were assessed by using the unilateral hot plate test, as described (38). Mechanical sensitivity was assessed using a modification of the Randall-Selitto test (39) and von Frey filaments as described (40).…”

Section: Methodsmentioning

confidence: 99%

Metalloproteinase MT5-MMP is an essential modulator of neuro-immune interactions in thermal pain stimulation

Folgueras

Valdés-Sánchez²,

Llano³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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Peripheral interactions between nociceptive fibers and mast cells contribute to inflammatory pain, but little is known about mechanisms mediating neuro-immune communication. Here we show that metalloproteinase MT5-MMP (MMP-24) is an essential mediator of peripheral thermal nociception and inflammatory hyperalgesia. We report that MT5-MMP is expressed by CGRP-containing peptidergic nociceptors in dorsal root ganglia and that Mmp24-deficient mice display enhanced sensitivity to noxious thermal stimuli under basal conditions. Consistently, mutant peptidergic sensory neurons hyperinnervate the skin, a phenotype that correlates with changes in the regulated cleavage of the cell-cell adhesion molecule N-cadherin. In contrast to basal nociception, Mmp24 ؊/؊ mice do not develop thermal hyperalgesia during inflammation, a phenotype that appears associated with alterations in N-cadherin-mediated cell-cell interactions between mast cells and sensory fibers. Collectively, our findings demonstrate an essential role of MT5-MMP in the development of dermal neuro-immune synapses and suggest that this metalloproteinase may be a target for pain control.inflammation ͉ mast cell ͉ N-cadherin

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Section: Methodsmentioning

confidence: 99%

Metalloproteinase MT5-MMP is an essential modulator of neuro-immune interactions in thermal pain stimulation

Folgueras

Valdés-Sánchez²,

Llano³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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“…To further determine the contribution of RAGE to diabetes-induced loss of pain perception, indicative of long-standing diabetic neuropathy, mice were tested for thermonociception using the hot-plate test at 50-55°C (38,39). When healthy β-globin transgenic mice (see also Figure 2C) were compared with littermates that had had STZinduced diabetes for 3 months, pain perception in diabetic mice was significantly reduced (Figure 5), and lifting, licking, and jump latency at 55°C declined from 7.3 ± 2.1 seconds to 11.4 ± 4.6 seconds (P = 0.0005).…”

Section: Figurementioning

confidence: 99%

“…Thermal nociception was studied using the hot-plate test with an electronically controlled hot-plate analgesia meter (Columbus Instruments) at 50°C and 55°C (38,39). Each mouse was removed from the hot plate when a jumping escape response occurred or hind paws were licked, or after a maximal cutoff time of 60 seconds (50°C) or 50 seconds (55°C) was reached.…”

Section: Measurement Of Pain Perceptionmentioning

confidence: 99%

Loss of pain perception in diabetes is dependent on a receptor of the immunoglobulin superfamily

Bierhaus¹,

Haslbeck²,

Humpert³

et al. 2004

J. Clin. Invest.

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Molecular events that result in loss of pain perception are poorly understood in diabetic neuropathy. Our results show that the receptor for advanced glycation end products (RAGE), a receptor associated with sustained NF-κB activation in the diabetic microenvironment, has a central role in sensory neuronal dysfunction. In sural nerve biopsies, ligands of RAGE, the receptor itself, activated NF-κBp65, and IL-6 colocalized in the microvasculature of patients with diabetic neuropathy. Activation of NF-κB and NF-κB-dependent gene expression was upregulated in peripheral nerves of diabetic mice, induced by advanced glycation end products, and prevented by RAGE blockade. NF-κB activation was blunted in RAGE-null (RAGE -/-) mice compared with robust enhancement in strain-matched controls, even 6 months after diabetes induction. Loss of pain perception, indicative of long-standing diabetic neuropathy, was reversed in WT mice treated with soluble RAGE. Most importantly, loss of pain perception was largely prevented in RAGE -/-mice, although they were not protected from diabetes-induced loss of PGP9.5-positive plantar nerve fibers. These data demonstrate, for the first time to our knowledge, that the RAGE-NF-κB axis operates in diabetic neuropathy, by mediating functional sensory deficits, and that its inhibition may provide new therapeutic approaches.

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“…Mice were gently restrained, and the plantar side of the tested paw was placed on a hot plate surface as described previously (Menéndez et al, 2002). The latency of paw withdrawal from the heated surface was manually recorded with a chronometer.…”

mentioning

confidence: 99%

An Inhibitor of Neuronal Exocytosis (DD04107) Displays Long-Lasting In Vivo Activity against Chronic Inflammatory and Neuropathic Pain

Ponsati¹,

Carreño²,

Curto-Reyes³

et al. 2012

J Pharmacol Exp Ther

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Small peptides patterned after the N terminus of the synaptosomal protein of 25 kDa, a member of the protein complex implicated in Ca 2ϩ -dependent neuronal exocytosis, inhibit in vitro the release of neuromodulators involved in pain signaling, suggesting an in vivo analgesic activity. Here, we report that compound DD04107 (palmitoyl-EEMQRR-NH 2 ), a 6-mer palmitoylated peptide that blocks the inflammatory recruitment of ion channels to the plasma membrane of nociceptors and the release of calcitonin gene-related peptide from primary sensory neurons, displays potent and long-lasting in vivo antihyperalgesia and antiallodynia in chronic models of inflammatory and neuropathic pain, such as the complete Freund's adjuvant, osteosarcoma, chemotherapy, and diabetic neuropathic models. Subcutaneous administration of the peptide produced a dose-dependent antihyperalgesic and antiallodynic activity that lasted Ն24 h. The compound showed a systemic distribution, characterized by a bicompartmental pharmacokinetic profile. Safety pharmacology studies indicated that the peptide is largely devoid of side effects and substantiated that the in vivo activity is not caused by locomotor impairment. Therefore, DD04107 is a potent and long-lasting antinociceptive compound that displays a safe pharmacological profile. These findings support the notion that neuronal exocytosis of receptors and neuronal algogens pivotally contribute to chronic inflammatory and neuropathic pain and imply a central role of peptidergic nociceptor sensitization to the pathogenesis of pain.

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Unilateral hot plate test: a simple and sensitive method for detecting central and peripheral hyperalgesia in mice

Cited by 126 publications

References 18 publications

Metalloproteinase MT5-MMP is an essential modulator of neuro-immune interactions in thermal pain stimulation

Metalloproteinase MT5-MMP is an essential modulator of neuro-immune interactions in thermal pain stimulation

Loss of pain perception in diabetes is dependent on a receptor of the immunoglobulin superfamily

An Inhibitor of Neuronal Exocytosis (DD04107) Displays Long-Lasting In Vivo Activity against Chronic Inflammatory and Neuropathic Pain

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