Neuropathic pain - page 4 Scientific Publications

Latest publication 04/13/2021

Methylmercury induces hyperalgesia and allodynia through spinal cord dorsal horn

Methylmercury (MeHg) is known to cause serious neurological deficits in humans. In this study, we investigated the occurrence of MeHg-mediated...

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    [title] => Methylmercury induces hyperalgesia and allodynia through spinal cord dorsal horn
    [paragraph] => Methylmercury induces hyperalgesia and allodynia through spinal cord dorsal horn neuronal activation and subsequent somatosensory cortical circuit formation in rats
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Authors
M Fujimura, F Usuki, A Nakamura  et al

 Lab
Department of Basic Medical Sciences, National Institute for Minamata Disease, Kumamoto, Japan
Journal
Archives of Toxicology
Abstract
Methylmercury (MeHg) is known to cause serious neurological deficits in humans. In this study, we investigated the occurrence of MeHg-mediated neuropathic pain and identified the underlying pathophysiological mechanism in a rat model of MeHg exposure. Rats were exposed to MeHg (20 ppm in drinking water) for 3 weeks. Neurological damage was observed in the primary afferent neuronal system, including the dorsal root nerve and the dorsal column of the spinal cord. The MeHg-exposed rats showed hyperalgesia/allodynia, compared to controls, as evidenced by a significant decrease in the threshold of mechanical pain evaluated using an algometer with calibrated forceps. Immunohistochemistry revealed the accumulation of activated microglia in the dorsal root nerve, dorsal column, and dorsal horn of the spinal cord. Western blot analyses of the dorsal part of the spinal cord demonstrated an increase in inflammotoxic and inflammatory cytokines and a neuronal activation related protein, phospho-CRE bunding protein (CREB). The results suggest that dorsal horn neuronal activation was mediated by inflammatory factors excreted by accumulated microglia. Furthermore, analyses of the cerebral cortex demonstrated increased expression of phospho-CREB and thrombospondin-1, which is known to be an important factor for excitatory synapse formation, specifically in the somatosensory cortical area. In addition, the expression of pre- and post-synaptic markers was increased in this cortex area. These results suggested that the new cortical circuit was wired specifically in the somatosensory cortex. In conclusion, MeHg-mediated dorsal horn neuronal activation with inflammatory microglia might induce somatosensory cortical rewiring, leading to hyperalgesia/allodynia.
BIOSEB Instruments Used
Rodent pincher - analgesia meter (BIO-RP-M)
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A fast and accurate algometer based on an instrumented pincher as an alternative to the Randall-Selitto test: This new analgesia meter developed by Bioseb following Luis-Delgado et al. (2005) allows accurate nociceptive tests to measure mechanical pain threshold on rat or mouse limbs with minimal constraint. Now wireless, to be free from annoying cables!

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