Ab

TTX-resistant TTX sensitive

Figure 5 Sodium channels in visceral sensory neurons. (A) Gastric sensory neurons express TTX-resistant (left panel) and TTX-sensitive (right panel) sodium currents. (B) Experimental ulcers increase the peak of TTX-resistant but not TTX-sensitive sodium currents in gastric sensory neurons. Abbreviation: TTX, tetrodotoxin.

TTX-resistant TTX sensitive

Figure 5 Sodium channels in visceral sensory neurons. (A) Gastric sensory neurons express TTX-resistant (left panel) and TTX-sensitive (right panel) sodium currents. (B) Experimental ulcers increase the peak of TTX-resistant but not TTX-sensitive sodium currents in gastric sensory neurons. Abbreviation: TTX, tetrodotoxin.

expression observed after axotomy (78). Similarly, addition of NGF increases TTX-resistant sodium currents in cultured sensory neurons, while NGF depletion using neutralizing antibodies decreases sodium currents (40,79).

Most of the experiments investigating the role of VSSC focused on the pore-forming a subunit of the channel complex. However, several associated proteins have been identified that modulate channel insertion into the membrane and channel function. In the case of VSSC, three different P subunits can coassemble with the a subunit and significantly increase peak amplitude and alter kinetics of sodium currents (80). Injury and inflammation differentially affect the expression of these associated subunits, which may lead to some of the functional changes observed (81).

While many studies support the importance of VSSC in pain syndromes, the translation of this information into new therapies has been slow. Several anticonvulsive and antiarrhyth-mic agents block VSSC and have been used to treat patients with chronic pain syndromes (82,83). Moreover, some peripherally active k opioid agonists and tricyclic antidepressants cause a use-dependent inhibition of sodium currents, which may contribute to their effectiveness in visceral pain syndromes (84-86). However, the lack of selectivity with cardiac and neurological side effects limits the utility of these agents in pain management.

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