Gabapentin Attenuates the Activation of Transient Receptor Potential A1 by Cinnamaldehyde

Abstract

Gabapentin is used as an effective drug for relieving pain, but the main mechanism is still unclear. Recently, voltage-gated Ca 2＋ channel subunits are suggested for the main target for the analgesic action of gabapentin. We wonder whether gabapentin directly modulates other specific ion channels peripherally expressed in the sensory neurons. To test this, we used a heterologous expression system in which the cell lines transiently expressed thermosensitive transient receptor potential ion channels (thermoTRPs) as well as the primary cultured mouse trigeminal neurons. The application of gabapentin reduced the increases in the intracellular Ca 2＋ level caused by TRPA1 activation in the heterologous expression system whereas the responses via actions of other thermoTRPs were not dramatically affected by the gabapentin treatment. Gabapentin also attenuated the TRPA1-mediated intracellular Ca 2＋ increases in the cultured trigeminal neurons. These findings suggest TRPA1 in the peripheral sensory neurons as a novel target for the analgesic of gabapentin.

Effect of Gabapentin-Fluoxetine Derivative GBP1F in a Murine Model of Depression, Anxiety and Cognition

“… 3 Such inherent actions are positively conducive towards amelioration of the emotional component of pain, in addition to a core effectiveness in relieving pain centrally via transient receptor channels and voltage-gated Ca 2+ channel subunits. 35 , 36 In our study, GBP1F had a behavioral antidepressant-like effect at all doses studied. Additionally, there was evidence that the tissue concentration of dopamine was enhanced by GBP1F and gabapentin in the striatum and it is of note that dopamine has been implicated in modulating both glutamate and GABA via L-type calcium channels.…”

Neurogenic rosacea in Korea

“…31 Gabapentin, pregabalin and duloxetine may exert therapeutic effect by blocking this pathway. [32][33][34][35] Moreover, analgesic effects of duloxetine have been reported in complex regional pain syndrome, fibromyalgia and other pain disorders. 36,37 Benzodiazepines that are c-aminobutyric acid agonists have analgesic effects on the spinal cord and can reduce catecholamines in the peripheral nervous system.…”

“…Although the pathway leading to neurovascular dysfunction in rosacea is not well known, there is a theory that transient receptor potential vanilloid 1 and transient receptor potential ankyrin 1, when activated by triggers such as heat or spicy food, stimulate the secretion of vasoactive peptides 31 . Gabapentin, pregabalin and duloxetine may exert therapeutic effect by blocking this pathway 32–35 . Moreover, analgesic effects of duloxetine have been reported in complex regional pain syndrome, fibromyalgia and other pain disorders 36,37 .…”

Short-term incubation of gabapentin or pregabalin does not affect chemically induced injury in neuronal cell models in vitro

“…For instance, in addition to the well-described interaction with voltage-gated calcium channels, 38 gabapentinoids likely also inhibit N -methyl-D-aspartate receptors 39 , 40 and suppress protein kinase C 41 and transient receptor-potential A ion channels. 42 They might also reduce γ-aminobutyric acidergic activity in the locus coeruleus and induce glutamate release in astrocytes. 43 , 44 Therefore, future research should address this complexity by employing neuronal–glial cocultures, brain slices, or whole animals instead of single-cell models.…”