What are some of the molecules that are unique to the nociceptor?
All nociceptors use glutamate as their primary excitatory neurotransmitter. However, several other transmitters coexist with glutamate, and the differences in transmitters define the two major classes of nociceptors: The peptidergic class expresses calcitonin gene-related peptide (CGRP) and substance P. The non-peptide class is characterized by its binding of a unique lectin (IB4) and the fact that many of these neurons express the P2X3 purinergic receptor, which responds to adenosine triphosphate (ATP). Whether these classes mediate different types of pain remains to be determined; however, recent tracing studies indicate that the different subsets of nociceptors engage different circuits in the spinal cord and different ascending pathways.
A molecule that is present only in C fiber nociceptors and that is relevant to the transmission of nociceptive messages is a possible therapeutic drug target. This is because the side effect profile of such a drug would be limited by the fact that it is less likely to bind to unwanted sites in the central or peripheral nervous system. The cell bodies of small-diameter neurons in the dorsal root ganglion (which are the cell bodies of C fibers) contain several unique molecules, including the following:
- • A tetrodotoxin-resistant Na channel (TTX-R)
- • The vanilloid receptor (TRPV1), which is targeted by capsaicin, the active ingredient in hot peppers (See TRP channels, below)
- • TRPM8, which responds to cool temperatures and to menthol
- • The P2X3 subtype of purinergic receptor, which is targeted by ATP
- • A special type of dorsal root ganglion specific acid-sensing ion channel (DRASIC)