ABSTRACT
Pain is a critical protective mechanism that allows healthy animals to avoid tissue damage and to prevent further damage to injured tissue. It allows people and animals to learn the physical constraints of their bodies and to identify dangerous stimuli. People who lack normal pain sensation have great diculty in establishing their physical boundaries and as a result often
40.1.1 Pain pathways 596 40.1.2 Nociceptive neurons 596
40.2 Voltage-gated sodium channels 597 40.3 NaV1.3 598
40.3.1 NaV1.3 localization and role in nociceptor signaling 598 40.3.2 NaV1.3 biophysics 598 40.3.3 NaV1.3 in sympathetic neurons 598 40.3.4 Genetic manipulation of NaV1.3 in animal pain models 598
40.4 NaV1.7 598 40.4.1 NaV1.7 localization and role in nociceptor signaling 598 40.4.2 NaV1.7 biophysics 598 40.4.3 NaV1.7 human genetics 598 40.4.4 NaV1.7 in animal pain models 599 40.4.5 NaV1.7 pharmacology 599
40.5 NaV1.8 599 40.5.1 NaV1.8 localization and role in nociceptor signaling 599 40.5.2 NaV1.8 in animal pain models 600 40.5.3 NaV1.8 human data 600 40.5.4 NaV1.8 pharmacology 600
40.6 NaV1.9 601 40.6.1 NaV1.9 localization and role in nociceptor signaling 601 40.6.2 NaV1.9 biophysics 601 40.6.3 NaV1.9 in animal pain models 601
40.7 TRPV1 601 40.7.1 TRPV1 localization and role in nociceptor signaling 601 40.7.2 TRPV1 in animal pain models 602 40.7.3 TRPV1 pharmacology 602
40.8 CaV2.2 603 40.8.1 CaV2.2 localization and role in nociceptor signaling 603 40.8.2 CaV2.2 in animal pain models 603 40.8.3 CaV2.2 pharmacology 603
40.9 Other channels linked to pain 603 40.10 Conclusions 604 References 604
inadvertently injure themselves. For example, mutations that prevent proper expression of the nerve growth factor receptor Trk-A (1) or the voltage-gated sodium (NaV) channel NaV1.7 confer complete congenital insensitivity to pain in humans (2). ese patients invariably injure themselves by biting their lips, tongues, and ngers in infancy and suer frequent self-injury throughout early life until they learn how to avoid harm. Even with vigilance, a mild injury like a foot blister, which would be quickly noticed and remedied by most people, can go unnoticed in the absence of pain and progress to a serious skin lesion before it is discovered.
