Sensory Neuron Specific Ca21 Channels

The contention that certain voltage-gated Ca2+ channels on sensory neurons are of relevance to visceral pain is based on the antinociceptive effect of gabapentin and pregabalin, two anti-convulsant drugs with high affinity for the a2d1 Ca2+ channel subunit in DRG neurons (197,202,203). Gabapentin and pregabalin are able to counteract the colonic hyperalgesia elicited by septic shock (204) and inflammation due to TNBSA (205). The writhing response to intraperitoneal injection of acetic acid is also inhibited by gabapentin (206). Since pregabalin does not alter the visceromotor response to distension of the normal colon (205), it is inferred that pregabalin-sensitive Ca2+ channels play a specific role in inflammation-evoked sensitization of GI afferents. Another Ca2+ channel targeted by analgesic drugs is the high voltage-gated N-type Ca2+ channel, which is of paramount importance for transmitter release. Inhibition of this channel by intrathecal administration of ziconotide affords relief from chronic pain by blocking transmitter release from the central terminals of spinal afferent neurons (207). In this way, ziconotide also suppresses the spinal transmission of nociceptive information from mesenteric afferents (208).

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