Nociception sodium channels

Several molecules participate in chemical stimulus detection 930 Sodium channels are key in conveying nociceptive information from the periphery to the CNS 930... 

Local application of concentrated sodium channel blockers can provide complete pain relief through nerve conduction block (local anesthetics). This approach to pain relief is limited to a few applications involving short-term treatment of acute pain, since sodium channels are also vital to conduction in the heart, CNS, skeletal muscle, and non-nociceptive sensory neurons. However, some types of chronic pain signaling appear to be sensitive to sodium channel blockers at concentrations that do not cause conduction block. In particular, neuropathic pain, defined as chronic pain resulting from a primary lesion or dysfunction of the peripheral nervous system by the International Association for the Study of Pain (IASP) [58], is thought to originate from aberrant signaling in the nervous system and can be ameliorated by sodium channel blockers. 

Priest BT, Murphy BA, Lindia JA, Diaz C, Abbadie C, Ritter AM, Liberator P, Iyer LM, Kash SF, Kohler MG, Kaezorowski GJ, MacIntyre DE, Martin WJ (2005) Contribution of the tetrodotoxin-resistant voltage-gated sodium channel NaVl.9 to sensory transmission and nociceptive behavior. PNAS 102 9382-9387... 

Walker, J.R., Novick, P.A., Parsons, W.H., et al., 2013. Marked difference in saxitoxin and tetrodoxin affinity for the human nociceptive voltage-gated sodium channel (Navi. 7). Proc. Nat. Acad. Sci. 109 (44), 18102-18107. 

Fig. 4.1 Hypothetical model of pathogenesis of pain in DSP. (1) Injury of peripheral nerve fibers due to multifocal inflammation and secreted macrophage activation products results in abnormal spontaneous activity of neighboring uninjured nociceptive fibers ( peripheral sensitization ). (2) Furthermore, the aberrant inflammatory response in DRG leads to alterations in neuronal sodium and calcium channel expression and ectopic impulse generation. (3) This results in central remodeling within the dorsal horn due to A-fiber sprouting and synaptic formation with pain fibers in lamina 11, and maintenance of neuropathic pain ( central sensitization ). Reproduced with permission from (Keswani et al. 2002)...

AMPA receptors are a family of proteins that line sodium ion channels expressed in the brain, spinal cord, dorsal root, and periphery. These receptors transmit both sensory and nociceptive stimuli. Transmission mediated by AMPA is believed to play an important role in wind-up and central plasticity. Thus, it is an important component in persistent pain states. Antagonists of the AMPA receptor have significant analgesic potential however, the well-known side effects of ataxia and sedation have hampered their development. 

---