The Calcium Channel Blocker Gabapentin, a Benchmark Drug in Pain Studies, Inhibits Translocation of the Epsilon Isoform of Protein Kinase C in Cultured Nociceptors: A Novel Mechanism of Action

Gabapentin is a well-established anticonvulsant medication that is also beneficial in the treatment of pain associated with neuropathy. Gabapentin, a structural analogue of the gamma-aminobutyric acid inhibitory neurotransmitter, was first formulated as a third-generation antiepileptic drug in the early 1990s. Although the precise mechanism for relieving allodynia and hyperalgesia triggered by neuropathy is not understood, it has been hypothesized that the blocking effect of gabapentin on voltage-dependent calcium channels is involved. The effectiveness of gabapentin on protein kinase C epsilon (PKCε) translocation in cultured peripheral neurons isolated from rat dorsal root ganglia was tested in order to further assess its analgesic mechanisms (DRGs). We observed that gabapentin significantly decreased the translocation of PKCε caused by the bradykinin and prokineticin 2 pronociceptive peptides, which are involved in both inflammatory and chronic pain. We have recently shown that PKCε inhibition is also provided by paracetamol (acetaminophen), a very widely used analgesic medication. The effect of the combined use of paracetamol and gabapentin has been tested and we have found that translocation inhibition adds up in a non-cooperative way. Our research offers a novel mechanism of action for gabapentin in sensory neurons and indicates a justification and mechanism of action for the combined use of paracetamol and gabapentin, which has recently been shown to be effective in treating postoperative pain in human patients through cumulative actions.

Author (s) Details

Vittorio Vellani
Dipartimento di Scienze Biomediche, Metaboliche e Neuroscienze, Università di Modena e Reggio Emilia, Via Campi 287, 41125 Modena, Italy.

Chiara Giacomoni
Dipartimento di Economia, Scienze e Diritto, Università degli Studi della Repubblica di San Marino, via Consiglio dei Sessanta 99, 47891 Dogana, Repubblica di San Marino.

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