Downregulation of GABAB receptors in the spinal cord dorsal horn in diabetic neuropathy

Wang, Xiuli; Zhang, Qi; Zhang, Yingze; Liu, Yantao; Dong, Rui; Wang, Qiujun; Guo, Yuexian

doi:10.1016/j.neulet.2010.12.038

Cited by 37 publications

(22 citation statements)

References 33 publications

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“…Although the most parsimonious explanation for our findings is that depressed C‐fiber field potential is due to A‐fiber‐evoked activation of local circuits, other mechanisms are possible. That genetic (Schuler et al ., ; Gassmann et al ., ) or diabetes mellitus‐induced (Wang et al ., ) impairment of GABA B receptors decreases thermal and mechanical thresholds and that pharmacological inhibition of segmental GABA B receptors facilitates both C fiber‐evoked neuronal and field potential responses in DH (present results; Sokal & Chapman, ; Buesa et al ., ) suggest that there is a GABA B receptor‐related tone. Glycinergic/GABA A ergic disinhibition might facilitate tonic GABA B ‐mediated inhibition.…”

Section: Discussionsupporting

confidence: 67%

Segmental disinhibition suppresses C‐fiber inputs to the rat superficial medullary dorsal horn via the activation of GABA_B receptors

Mélin

Jacquot

Dallel

et al. 2012

Eur J of Neuroscience

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Specialized primary afferents, although they terminate in different laminae within the dorsal horn (DH), are known to interact through local circuit excitatory and inhibitory neurons. That a loss of segmental inhibition probably contributes to persistent pain hypersensitivity during chronic pain raises the question as to how disinhibition-induced changes in cross-modal interactions account for chronic pain symptoms. We sought to characterize how pharmacological blockade of glycine and gamma-aminobutyric acid (GABA) receptors modifies synaptic transmission between primary afferent fibers and second-order neurons by recording field potentials in the superficial medullary dorsal horn (MDH) of anesthetized rats. Transcutaneous electrical stimulation evokes three negative field potentials elicited by, from earliest to latest, Aβ-, Aδ- and C-fiber primary afferents. Blocking segmental glycine and/or GABA(A) receptors, with strychnine and bicuculline, respectively, strongly facilitates Aβ- and Aδ-fiber-evoked polysynaptic field potentials but, conversely, inhibits, or even abolishes, the whole C-fiber field potential. Blocking segmental GABA(B) receptors, with phaclofen, reverses such suppression of C-fiber field potentials. Interestingly, it also potentiates C-fiber field potentials under control conditions. Finally, activation of segmental GABA(B) receptors, with baclofen, preferentially inhibits C-fiber field potentials. Our results suggest that activation of A-fiber primary afferents inhibits C-fiber inputs to the MDH by the way of polysynaptic excitatory pathways, last-order GABAergic interneurons and presynaptic GABA(B) receptors on C-fiber primary afferents. Under physiological conditions, activation of such local DH circuits is closely controlled by segmental inhibition but it might contribute to paradoxically reduced pain hypersensitivity under pathological disinhibition.

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Section: Discussionsupporting

confidence: 67%

Segmental disinhibition suppresses C‐fiber inputs to the rat superficial medullary dorsal horn via the activation of GABA_B receptors

Mélin

Jacquot

Dallel

et al. 2012

Eur J of Neuroscience

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“…Many studies of Oxt in the DRG suggest that Aβ RA signals are changed to long‐lasting SA signals by Oxt with the aid of glia cells in the DRG . In addition, Oxt receptors and GABA receptors are located in the DH. The DH region seems to be the most efficient region where pain signals carried by Aδ/C fibers are reduced by long‐lasting Aβ SA fibers .…”

Section: Discussionmentioning

confidence: 99%

Adhesive pyramidal thorn patches provide pain relief to athletes

Saito

Shima

Yen

et al. 2019

The Kaohsiung J of Med Scie

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Pain in athletes is ideally treated without systemic medicine. Therefore, complementary and alternative medicine, including patch treatments, is often used. The physiologic mechanisms of pain relief produced by patch treatment, however, are not well elucidated. In the present study, we introduce a pyramidal thorn (PT) patch that we developed, demonstrate the effects of this PT patch for the treatment of various types of pain in 300 subjects, and suggest a physiologic mechanism for the pain relief effects. One treatment with the PT patch effectively relieved pain in almost half the subjects evaluated. Except for pain generated deeply under the skin, such as low‐back pain, pain was eliminated within four treatments with the PT patch in almost all of the subjects. Interestingly, the pain‐sensing region moved along the nerve fibers after each trial. Further, patches without PT also provided some pain relief. We considered that this effect was due to hair deflection on the skin; that is, adhesion of the PT patch activates Merkel cells directly as well as Merkel cell‐neurite complexes around the hair follicles by deflecting the hair follicles, whereas adhesion of a patch without PT only activates the Merkel cell‐neurite complexes. In any case, patch adhesion stimulates Aβ fibers to alleviate pain. Finally, we found that the pain threshold is increased by electric stimulation, suggesting that the gentle adhesion of a PT patch would be more effective. To our knowledge, this is the first study to demonstrate physiologically the validity of an adherent patch for pain relief.

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“…Moreover, ongoing GABA A receptor activity directly contributes to allodynic and hyperalgesic behavior of diabetic rats as both disorders can be alleviated by spinal delivery of GABA A antagonists (Jolivalt et al, 2008b). The inversion of GABA receptor function towards excitation is restricted to the ionotrophic GABA A receptor, as metabotrophic GABA B receptors retain their inhibitory role (Lee-Kubli and Calcutt, unpublished observations), despite recent evidence that their expression may be reduced as diabetes progresses (Wang et al, 2011). KCC2 expression in the brain and spinal cord of normal animals is regulated by local BDNF, with increased BDNF suppressing KCC2 protein expression (Coull et al, 2005;Miletic and Miletic, 2008;Lu et al, 2009;Lee-Kubli and Calcutt, 2014).…”

Section: Disinhibitionmentioning

confidence: 99%

Painful neuropathy

Lee-Kubli

Calcutt

2014

Diabetes and the Nervous System

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Downregulation of GABAB receptors in the spinal cord dorsal horn in diabetic neuropathy

Cited by 37 publications

References 33 publications

Segmental disinhibition suppresses C‐fiber inputs to the rat superficial medullary dorsal horn via the activation of GABA_B receptors

Segmental disinhibition suppresses C‐fiber inputs to the rat superficial medullary dorsal horn via the activation of GABA_B receptors

Adhesive pyramidal thorn patches provide pain relief to athletes

Painful neuropathy

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Downregulation of GABAB receptors in the spinal cord dorsal horn in diabetic neuropathy

Cited by 37 publications

References 33 publications

Segmental disinhibition suppresses C‐fiber inputs to the rat superficial medullary dorsal horn via the activation of GABAB receptors

Segmental disinhibition suppresses C‐fiber inputs to the rat superficial medullary dorsal horn via the activation of GABAB receptors

Adhesive pyramidal thorn patches provide pain relief to athletes

Painful neuropathy

Contact Info

Product

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Segmental disinhibition suppresses C‐fiber inputs to the rat superficial medullary dorsal horn via the activation of GABA_B receptors

Segmental disinhibition suppresses C‐fiber inputs to the rat superficial medullary dorsal horn via the activation of GABA_B receptors