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Eur J Pharmacol. 2019 Aug 28;862:172631. doi: 10.1016/j.ejphar.2019.172631. [Epub ahead of print]

Spinal TASK-1 and TASK-3 modulate inflammatory and neuropathic pain.

Author information

1
Departamento de Farmacobiología, Cinvestav, Sede Sur, Ciudad de México, Mexico.
2
Unidad de Investigación Médica en Inmunología e Infectología, Centro Médico Nacional, La Raza, Instituto Mexicano del Seguro Social, Ciudad de México, Mexico.
3
Departamento de Farmacobiología, Cinvestav, Sede Sur, Ciudad de México, Mexico. Electronic address: jmurbartian@gmail.com.

Abstract

This study assessed the participation of spinal TWIK-related acid-sensitive K+ channels 1 and 3 (TASK-1 and TASK-3) in inflammatory (formalin test) and neuropathic (spinal nerve ligation, SNL) pain in rats. Intrathecal pre-treatment (-10 min) with the TASK-1 blocker ML365 or TASK-3 blocker PK-THPP, but not vehicle, enhanced in a dose-dependent manner 1% formalin-induced acute and long-lasting secondary mechanical allodynia and mechanical hyperalgesia in rats. In contrast, intrathecal pre-treatment with terbinafine, an activator of TASK-3, reduced formalin-induced flinching and allodynia/hyperalgesia. Both blockers and terbinafine had similar effects on female and male rats. In addition, intrathecal injection of ML365 or PK-THPP blocked the terbinafine-induced antiallodynic effect in neuropathic rats, but they did not modify baseline withdrawal threshold in naïve or sham-operated rats. TASK-1 and TASK-3 mRNA and protein were expressed in L4 and L5 dorsal root ganglia (DRG) and dorsal and ventral spinal cord of naïve animals. Interestingly, formalin injection increased TASK-1 expression in ipsilateral L5 DRG, but not in the spinal cord. Moreover, formalin injection transiently enhanced TASK-3 expression in ipsilateral L5 DRG and dorsal spinal cord. In contrast, SNL down-regulated TASK-3 expression in the ipsilateral L4 and L5 DRG but not in dorsal or ventral spinal cord, while SNL did not modify TASK-1 expression at any tissue. The pharmacological and molecular results suggest that TASK-1 and TASK-3 have a relevant antinociceptive role in inflammatory and neuropathic pain.

KEYWORDS:

Allodynia; Hyperalgesia; Inflammatory pain; Neuropathic pain; TASK-1; TASK-3

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