11 February 2019
Neuropathic pain resulting from peripheral nerve lesions is a common medical condition, but current analgesics are often insufficient. The identification of key molecules involved in pathological pain processing is a prerequisite for the development of new analgesic drugs. Hyperexcitability of nociceptive DRG-neurons due to regulation of voltage-gated ion-channels is generally assumed to contribute strongly to neuropathic pain. There is increasing evidence, that T-type Ca 2+-currents and in particular the Ca v3.2 T-type-channel isoform play an important role in neuropathic pain, but experimental results are contradicting.
To clarify the role of T-type Ca 2+-channels and in particular the Ca v3.2 T-type-channel isoform in neuropathic pain.
The effect of partial sciatic nerve ligation (PNL) on pain behavior and the properties of T-type-currents in nociceptive DRG-neurons was tested in wild-type and Ca v3.2-deficient mice.
In wild-type mice, PNL of the sciatic nerve caused neuropathic pain and an increase of T-type Ca 2+-currents in capsaicin-responsive neurons, while capsaicin-unresponsive neurons were unaffected. Pharmacological experiments revealed that this upregulation was due to an increase of a Ni 2+-resistant Ca 2+-current component, inconsistent with Ca v3.2 up-regulation. Moreover, following PNL Ca v3.2-deficient mice showed neuropathic pain behavior and an increase of T-Type Ca 2+-currents indistinguishable to that of PNL treated wild-type mice.
These data suggest that PNL induces an upregulation of T-Type Ca 2+-currents in capsaicin-responsive DRG-neurons mediated by an increase of a Ni 2+-insensitive current component (possibly Ca v3.1 or Ca v3.3). These findings provide relevance for the development of target specific analgesic drugs.