Use-dependent blockade of Cav2.2 voltage-gated calcium channels for neuropathic pain

Inhibition of Transmitter Release and Attenuation of Anti-retroviral-associated and Tibial Nerve Injury-related Painful Peripheral Neuropathy by Novel Synthetic Ca2+ Channel Peptides

“…Alternative splice variants found on small diameter nociceptive neurons are associated with increased thermal and mechanical hyperalgesia (50,51). CaV2.2 is believed to be responsible for increased neurotransmitter release commonly associated with chronic and neuropathic pain conditions (1,2,52,53). Consistent with the role of CaV2.2 in pain signaling, genetic deletion, as well as pharmacologic block of CaV2.2, impairs nociceptive processing (3,54).…”

Conus Venom Peptide Pharmacology

“…Many -conotoxins exhibit high potency and selectivity for different subtypes of voltage-gated calcium channels . The development of the N-type (Ca v 2.2) antagonist, -conotoxin MVIIA (SNX-111; ziconotide), as an intrathecal analgesic to manage moderate to severe chronic pain, provided the first validation of the use of -conotoxins and established Ca v 2.2 as new target for pain therapeutics (Lewis and Garcia, 2003;Winquist et al, 2005). Although ziconotide is potent and does not induce addiction or tolerance as opioids do (Malmberg and Yaksh, 1995;Bowersox et al, 1996), its use is limited because of the need for intrathecal administration combined with significant dose-limiting neurological side effects (Penn and Paice, 2000).…”

Novel Mechanism of Voltage-Gated N-type (Cav2.2) Calcium Channel Inhibition Revealed through α-Conotoxin Vc1.1 Activation of the GABAB Receptor

“…GABA B R is a potential target for drugs that treat neurologic illnesses, such as pain, epilepsy, spasticity, and psychiatric disorders (Marshall et al, 1999;Bowery et al, 2002). For example, inhibition of presynaptic HVA calcium channels, such as Ca v 2.2, has been linked to suppression of neurotransmitter release and block of nociception transmission (Winquist et al, 2005;Gribkoff, 2006).…”