Peripheral Glutamate Receptors Are Required for Hyperalgesia Induced by Capsaicin

Jin, Youhong; Takemura, Motohide; Furuyama, Akira; Yonehara, Norifumi

doi:10.1155/2012/915706

Cited by 14 publications

(12 citation statements)

References 31 publications

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“…Interestingly, when we removed Vglut2 specifically from the Trpv1-Cre neurons, the Vglut2 f/f ;Trpv1-Cre mice still developed inflammation-associated hyperalgesia with only a small reduction compared with control mice. Because activation of glutamatergic receptors is important for the development and transmission of heat hyperalgesia (Nakayama et al, 2010;Jin et al, 2012), we find it likely that other players compensate for the loss of VGLUT2-mediated glutamatergic transmission in the Trpv1-Cre population. VGLUT3 shows very little, if any, overlap with the TRPV1 population (Seal et al, 2009), but the TRPV1 population may coexpress VGLUT1, which could uphold a glutamatergic tone from the TRPV1 neurons.…”

Section: Discussionmentioning

confidence: 87%

Glutamate, Substance P, and Calcitonin Gene-Related Peptide Cooperate in Inflammation-Induced Heat Hyperalgesia

et al. 2013

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The transient receptor potential cation channel subfamily V member 1 (TRPV1) is known as a thermosensor and integrator of inflammation-induced hyperalgesia. TRPV1 is expressed in a subpopulation of primary afferent neurons that express several different neurotransmitters. The role of the TRPV1 channel in the development of hyperalgesia is established, but the role of the neurotransmitter glutamate, used partially by the same neuronal population and thus probably mediating the response, is still under investigation. We have used a Trpv1-Cre mouse line in which we either ablated Trpv1-Cre expressing neurons or induced vesicular glutamate transporter 2 (Vglut2) deficiency in Trpv1-Cre expressing neurons and investigated specific states of hyperalgesia after persistent inflammation. Furthermore, by pharmacologic inhibition of substance P (SP) or calcitonin gene-related peptide (CGRP) signaling in Vglut2-deficient mice, we also evaluated the contribution of SP or CGRP to inflammationinduced hyperalgesia, with or without the presence of vesicular glutamate transporter 2 (VGLUT2)-mediated glutamatergic transmission in Trpv1-Cre neurons. This examination, together with c-Fos analyses, showed that VGLUT2-mediated glutamatergic transmission in Trpv1-Cre afferents together with SP or CGRP is essential for the development of the heat hyperalgesia associated with persistent inflammation. Additionally, SP-, CGRP-, and VGLUT2-mediated transmission together were found to play a role in the development of mechanical hyperalgesia after persistent inflammation.

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Section: Discussionmentioning

confidence: 87%

Glutamate, Substance P, and Calcitonin Gene-Related Peptide Cooperate in Inflammation-Induced Heat Hyperalgesia

et al. 2013

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“…19 Interestingly, TRPV 1 and glutamate receptors also colocalize in nonvisceral small diameter primary afferent neurons and the induction of c-Fos expression in the spinal dorsal horn induced by subcutaneous capsaicin injection has been prevented by concomitant subcutaneous administration of ionotropic or metabotropic glutamatergic receptor antagonists. 20 Peripheral release of glutamate, likely from primary afferent nerve terminals, was noted in the hind paw skin of rats exposed to intraplantar injection of the irritant formalin. 21 Moreover, local injection of glutamate induces nociceptive behavior in rats 22 and humans.…”

Section: Discussionmentioning

confidence: 98%

Expression of Vesicular Glutamate Transporters in Sensory and Autonomic Neurons Innervating the Mouse Bladder

et al. 2013

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Purpose VGLUTs, which are essential for loading glutamate into synaptic vesicles, are present in various neuronal systems. However, to our knowledge the expression of VGLUTs in neurons innervating the bladder has not yet been analyzed. We studied VGLUT1, VGLUT2 and VGLUT3 in mouse bladder neurons. Materials and Methods We analyzed the expression of VGLUT1, VGLUT2 and calcitonin gene-related peptide by immunohistochemistry in the retrograde labeled primary afferent and autonomic neurons of BALB/c mice after injecting fast blue in the bladder wall. To study VGLUT3 we traced the bladder of transgenic mice, in which VGLUT3 is identified by enhanced green fluorescent protein detection. Results Most bladder dorsal root ganglion neurons expressed VGLUT2. A smaller percentage of neurons also expressed VGLUT1 or VGLUT3. Co-expression with calcitonin gene-related peptide was only observed for VGLUT2. Occasional VGLUT2 immunoreactive neurons were seen in the major pelvic ganglia. Abundant VGLUT2 immunoreactive nerves were detected in the bladder dome and trigone, and the urethra. VGLUT1 immunoreactive nerves were discretely present. Conclusions We present what are to our knowledge novel data on VGLUT expression in sensory and autonomic neurons innervating the mouse bladder. The frequent association of VGLUT2 and calcitonin gene-related peptide in sensory neurons suggests interactions between glutamatergic and peptidergic neurotransmissions, potentially influencing commonly perceived sensations in the bladder, such as discomfort and pain.

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“…Glutamate receptors (GluR) colocalized with TRPV1 on small diameter DRG neurons have been demonstrated to contribute to the activity of the capsaicin-induced TRPV1 sensitization [44] and GluR could possibly contribute to the finding in the present study that capsaicin-responsive neurons elicited larger Ca 2+ responses than neurons from capsaicin-unresponsive neurons (the difference was seen both in diabetic as well as control neurons).…”

Section: Discussionmentioning

confidence: 66%

Calcium Activity of Upper Thoracic Dorsal Root Ganglion Neurons in Zucker Diabetic Fatty Rats

Ghorbani

Nyborg

Fjalland

et al. 2013

International Journal of Endocrinology

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The aim of the present study was to examine the calcium activity of C8-T5 dorsal root ganglion (DRG) neurons from Zucker diabetic fatty rats. In total, 8 diabetic ZDF fatty animals and 8 age-matched control ZDF lean rats were employed in the study. C8-T5 dorsal root ganglia were isolated bilaterally from 14 to 18 weeks old rats, and a primary culture was prepared. Calcium activity was measured ratiometrically using the fluorescent Ca2+-indicator Fura-2 acetoxymethyl ester. All neurons were stimulated twice with 20 mM K+, followed by stimulation with either 0.3 or 0.5 μM Capsaicin, alone or in combination with algogenic chemicals (bradykinin, serotonin, prostaglandin E2 (all 10−5 M), and adenosine (10−3 M)) at pH 7.4 and 6.0. Neurons from diabetic animals exhibited an overall increased response to stimulation with 20 mM K+ compared to neurons from control. Stimulation with Capsaicin alone caused an augmented response in neurons from diabetic animals compared to control animals. When stimulated with a combination of Capsaicin and algogenic chemicals, no differences between the two groups of neurons were measured, neither at pH 7.4 nor 6.0. In conclusion, diabetes-induced alterations in calcium activity of the DRG neurons were found, potentially indicating altered neuronal responses during myocardial ischemia.

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Peripheral Glutamate Receptors Are Required for Hyperalgesia Induced by Capsaicin

Cited by 14 publications

References 31 publications

Glutamate, Substance P, and Calcitonin Gene-Related Peptide Cooperate in Inflammation-Induced Heat Hyperalgesia

Glutamate, Substance P, and Calcitonin Gene-Related Peptide Cooperate in Inflammation-Induced Heat Hyperalgesia

Expression of Vesicular Glutamate Transporters in Sensory and Autonomic Neurons Innervating the Mouse Bladder

Calcium Activity of Upper Thoracic Dorsal Root Ganglion Neurons in Zucker Diabetic Fatty Rats

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