Calcium channel functions in pain processing

Voltage-gated calcium channels (VGCC) play obligatory physiological roles, including modulation of neuronal functions, synaptic plasticity, neurotransmitter release and gene transcription. Dysregulation and maladaptive changes in VGCC expression and activities may occur in the sensory pathway under various pathological conditions that could contribute to the development of pain. In this review, we summarized the most recent findings on the regulation of VGCC expression and physiological functions in the sensory pathway, and in dysregulation and maladaptive changes of VGCC under pain-inducing conditions. The implications of these changes in understanding the mechanisms of pain transduction and in new drug design are also discussed

Silencing of the Ca(v)3.2 T-type calcium channel gene in sensory neurons demonstrates its major role in nociception

Analgesic therapies are still limited and sometimes poorly effective, therefore finding new targets for the development of innovative drugs is urgently needed. In order to validate the potential utility of blocking T-type calcium channels to reduce nociception, we explored the effects of intrathecally administered oligodeoxynucleotide antisenses, specific to the recently identified T-type calcium channel family (Ca(V)3.1, Ca(V)3.2, and Ca(V)3.3), on reactions to noxious stimuli in healthy and mononeuropathic rats. Our results demonstrate that the antisense targeting Ca(V)3.2 induced a knockdown of the Ca(V)3.2 mRNA and protein expression as well as a large reduction of ‘Ca(V)3.2-like' T-type currents in nociceptive dorsal root ganglion neurons. Concomitantly, the antisense treatment resulted in major antinociceptive, anti-hyperalgesic, and anti-allodynic effects, suggesting that Ca(V)3.2 plays a major pronociceptive role in acute and chronic pain states. Taken together, the results provide direct evidence linking Ca(V)3.2 T-type channels to pain perception and suggest that Ca(V)3.2 may offer a specific molecular target for the treatment of pain