TY - JOUR T1 - Implication of K<sub>v</sub>7 channels in the spinal antinociceptive actions of celecoxib JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther DO - 10.1124/jpet.119.258053 SP - jpet.119.258053 AU - Jorge Vicente-Baz AU - Jose A Lopez-Garcia AU - Ivan Rivera-Arconada Y1 - 2019/01/01 UR - http://jpet.aspetjournals.org/content/early/2019/06/24/jpet.119.258053.abstract N2 - Celecoxib is an NSAID commonly used to treat pain conditions in humans. In addition to its blocking activity on COXs enzymes, several other targets could contribute to its analgesic activity. Here we explore the spinal antinociceptive actions of celecoxib and the potential implication of Kv7 channels in mediating its effects. Spinal cord in vitro preparations from hind paw-inflamed animals were used to assess the segmental sensory-motor and the early sensory processing of nociceptive information. Electrophysiological recordings of ventral roots and dorsal horn neurones were obtained and the effects of celecoxib and Kv7 modulators on responses to repetitive dorsal root stimulation at C-fibre intensity were assessed. Celecoxib applied at clinically relevant concentrations produced depressant effects on responses to dorsal root stimulation recorded from both ventral roots and individual dorsal horn neurones, in contrast the non-nociceptive monosynaptic reflex was unaffected. The NSAID indomethacin was devoid of effect on spinal reflexes, but further co-application of celecoxib still produced depressant effects. The depressant actions of celecoxib were abolished after Kv7 channel blockade and mimicked by its structural analogue dimethyl-celecoxib that lacks COX blocking activity. The present results identify Kv7 channels as novel central targets for celecoxib that may be relevant to its analgesic effect. This finding contributes to better understand the pharmacology of celecoxib, and reinforces both the role of Kv7 channels in modulating the excitability of central pain pathways and its validity as target for the design of analgesics.SIGNIFICANCE STATEMENT N/A ER -