Mice lacking Kcns1 in peripheral neurons show increased basal and neuropathic pain sensitivity.
Pain
; 159(8): 1641-1651, 2018 Aug.
Article
em En
| MEDLINE
| ID: mdl-29697531
ABSTRACT
Voltage-gated potassium (Kv) channels are increasingly recognised as key regulators of nociceptive excitability. Kcns1 is one of the first potassium channels to be associated with neuronal hyperexcitability and mechanical sensitivity in the rat, as well as pain intensity and risk of developing chronic pain in humans. Here, we show that in mice, Kcns1 is predominantly expressed in the cell body and axons of myelinated sensory neurons positive for neurofilament-200, including Aδ-fiber nociceptors and low-threshold Aß mechanoreceptors. In the spinal cord, Kcns1 was detected in laminae III to V of the dorsal horn where most sensory A fibers terminate, as well as large motoneurons of the ventral horn. To investigate Kcns1 function specifically in the periphery, we generated transgenic mice in which the gene is deleted in all sensory neurons but retained in the central nervous system. Kcns1 ablation resulted in a modest increase in basal mechanical pain, with no change in thermal pain processing. After neuropathic injury, Kcns1 KO mice exhibited exaggerated mechanical pain responses and hypersensitivity to both noxious and innocuous cold, consistent with increased A-fiber activity. Interestingly, Kcns1 deletion also improved locomotor performance in the rotarod test, indicative of augmented proprioceptive signalling. Our results suggest that restoring Kcns1 function in the periphery may be of some use in ameliorating mechanical and cold pain in chronic states.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Limiar da Dor
/
Células do Corno Posterior
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Canais de Potássio de Abertura Dependente da Tensão da Membrana
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Neuralgia
Tipo de estudo:
Diagnostic_studies
Limite:
Animals
Idioma:
En
Revista:
Pain
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Reino Unido
País de publicação:
EEUU
/
ESTADOS UNIDOS
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ESTADOS UNIDOS DA AMERICA
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EUA
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UNITED STATES
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UNITED STATES OF AMERICA
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US
/
USA